Abstract:
A pharmaceutical preparation for prophylaxis and treatment of alcoholism comprises an active principle which is nicotinic acid lithium salt semihydrate of the formula: ##STR1## and a pharmaceutically acceptable vehicle.

Description:
FIELD OF THE INVENTION 
     The present invention relates to medicine and, more particularly, to a pharmaceutical preparation intended for the treatment and prophylaxis of alcoholism which is useful in psychyatry for therapy of chronic alcoholism and cutting-short of the alcoholic abstinent syndrome. It is also possible to use the preparation in healthy persons under stress conditions, since it possesses also stress-protective and tranquilizing properties. 
     Prior Art 
     Known in the art are various preparations possessing antialcoholic properties. They can be exemplified by preparations of sensitizing, aversive and psychotropic effects. Among them most widely employed are psychotropic preparations which differ advantageously from sensitizing and aversive preparations both in stability and duration of therapeutic remissions and in resocialization of patients suffering from alcoholism (Zdravookhranenie Tadzhikistana, No. 1, Jan. 1981/Dushanbe/, Kamolov Sh.K., Comparative Effectiveness of Antialcoholic Methods of Treatment, pp. 69-71). In this group of pharmaceutical preparations the highest activity is exhibited by neuroleptcis or tranquilizers especially based on derivatives of phenothiazine and benzodiazepine. However, in therapy of alcoholism neuroleptics produce pronounced side effects such as locomotive retardation, constraints, muscle twitching, parkinsonism phenomena and the like. Administration of benzodiazepine derivatives to such patients is also accompanied by a whole number of complications: development of toleration, formation of medicinal dependence. Since therapy of chronic alcoholism envisages a lasting administration of pharmaceutical preparations, the above-described phenomena are encountered far more frequently in the treatment of alcoholism than in the case of other psychopathological disturbances. The above-mentioned complications hinder a broad application of said prior art preparations as antialcoholic agents. 
     The data available from the literature point out that in pharmacotherapy of alcoholism especially active are pharmaceutical preparations based on lithium salts. Effectiveness of such preparations in the treatment of alcoholism is caused by the specific feature of lithium salts, residing in their ability of actively influence pathogenetic units of the process of development of alcoholism and accompanying affective disturbances, disorders of the emotional status. 
     Most widely used in the clinical practice are pharmaceutical preparations based on lithium chloride or lithium carbonate. Therapeutic activity of these preparations is revealed only under the conditions of their administration in high doses for creation of a high concentration of lithium in blood (1.5--2 mequiv/1) which necessitates a permanent laboratory control. Their administration in the above-specified doses is accompanied by side and toxic phenomena, especially pronounced on the part of kidneys. Furthermore, the preparation based on lithium carbonate has no soluble pharmaceutically acceptable form, while that based on lithium chloride has clearly pronounced hydroscopic properties. All this hampers a wide application of these preparations for the treatment of alcoholism. 
     SUMMARY OF THE INVENTION 
     It is an object of the present invention to provide a pharmaceutical preparation for prophylaxis and therapy of alcoholism, possessing a high effectiveness with absence of side and toxic effects in a suitable pharmaceutical form. 
     The object of the present invention is to provide a pharmaceutical preparation based on an active principle which, according to the present invention, is nicotinic acid lithium salt semihydrate of the general formula: ##STR2## in combination with a pharmaceutical acceptable vehicle. 
     It is advisable that the pharmaceutical preparation according to the present invention be used in the form of a solution for injections containing 10% by mass of the active principle in combination with a pharmaceutically acceptable vehicle such as distilled water or an isotonic solution. Such preparation accelerates arresting of the alcoholic abstinent syndrome, improves the accuracy of dosage and provides an opportunity of administration thereof in the case of a forced therapy of alcoholism. 
     For an ambulatory treatment and prevention of hard-drinking periods it is advisable to administer the pharmaceutical preparation according to the present invention in the form of pills containing 40% by mass of the active principle in combination with a pharmaceutically acceptable vehicle. 
     As the pharmaceutically acceptable vehicle use can be made of stearic acid, lactose, glucose, potato starch, talc. 
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
     To obtain nicotnic acid lithium salt semihydrate(lithium nicotinate semihydrate), lithium carbonate is mixed with nicotinic acid in equimolar amounts in 200 ml of distilled water. The reaction mixture is heated to the temperature of 90° C., and maintained at this temperature till complete dissolution of the reactants and stopping of evolution of carbon dioxide gas. The resulting solution is treated with 2 g of activated carbon in the presence of ethanol, cooled to a temperature of 10°-12° C., whereafter the resulting crystals of lithium nicotinate semihydrate are filtered-off and dried at a temperature of 105°-110° C. The total yield of the desired high-purity product is 80-98%. The resulting substance has not been hitherto described in the literature. The compound comprises a white crystalline powder having no odor, with a slight bitter taste. Stable in air. Readily soluble in water, sparingly soluble in absolutized ethanol. The pH of a 5% aqueous solution of the compound is 7.8-9.0 (potentiometrically). The 5% solution is colorless and transparent. With increasing concentration of the solution till saturation (45%) a yellow color appears, the solution acquires a viscous consistence, its specific gravity and refractive index are increased: 
     for a 1% solution ρ 4   20  =1.0077;η D   20  =1.3370 
     for a 44% solution ρ 4   20  =1.2428;η D   20  =1.4460 
     The electrical conductivity of diluted solutions of lithium nicotinate semihydrate is increased. The dissociation constant calculated from the data of molecular electrical conductivity measurements is equal to 5.6×10 3 . 
     The character of variations of these values made it possible to assume that in concentrated solutions and in solid state the resulting substance exists in the form of associates. 
     Thermogravimetric studies have shown that the compound is thermally stable at a temperature within the range of from 0° to 180° C. Dehydration occurs at a temperature of from 180° to 220° C.; clear-cut melting is absent; decomposition of the compound occurs at a temperature within the range of from 400° to 550° C. 
     The product is identified for nicotinic acid and lithium by gravimetric, iodometric and spectrophotometric methods. 
     Found, %: C 49.22, H 4.05, N 9.68, O 32.43, Li 4.62, nicotinic acid 89.0, lithium 4.7. 
     Calculated, %: C 49.10, H 4.11, N 9.58, O 32.47, Li 4.75, nicotinic acid 88.8, lithium 4.71. 
     Recording of spectra by the IR-spectroscopy method was effected under standardized conditions using a two-beam spectrophotometer IKS-14 with prisms within the range of from 4.000 to 650 cm -1 . Samples were pressed in tablets of potassium bromide. The test salt-lithium nicotinate semihydrate had the following characteristic lines: 3,370-3,228 cm -1  ; 14,020-1.400 cm -1  ; 1,310-1,290 cm -1  ; 850, 830 and 748 cm -1 . 
     The pharmaceutical preparation for prevention and treatment of alcoholism was obtained on the basis of lithium nicotinate semihydrate with the above-given characteristics. 
     To obtain an injection pharmaceutical form, a 10% solution of the active principle in distilled water or in an isotonic solution is prepared. 
     To obtain a pelletized pharmaceutical form (dragee) conventional techniques are employed (100 mg of the active principle per 250 mg of the total mass of dragee pellets) (i.e., 40% by mass). 
     The pharmaceutical preparation according to the present invention is stable. Its shelf life is 3 years. Storage conditions: in a dry, light-protected place. 
     The study of the specific activity of the preparation was performed in detail experimentally on white rats and on patients in clinics. 
     In experiments the animals were administered with intraperitoneal injections of the preparation in the dose of 10 mg/kg of the bodymass. This dosage has been established as a result of preliminary experiments. It has been shown that upon administration of the preparation in the dose of 1-3-5-7-9 mg/kg of the bodymass the therapeutic effect is not clearly pronounced. Upon administration of the preparation in a dose of from 15 to 25 mg/kg its efficiency is slightly diminished. The dose of 10 mg/kg turned to be optimal. 
     For the sake of convenience, nicotinic acid lithium salt semihydrate will be referred to hereinafter as lithium nicotinate. 
     The preparation according to the present invention in in vivo experiments on white nondescript rats reveals a high activity in therapy of analogs of psychological (I), physical (II) stages of the alcoholic dependence, as well as in its preventive use in the course of the formation of addition to ethanol and arresting of the alcoholic abstinent syndrome which opens a new perspective in prophylaxis and treatment of alcoholism. 
     Screening studies of lithium nicotinate were carried out following standard procedures developed in the Laboratory for finding and investigation of agents for therapy and prevention of narcomania at the Institute of Pharmacology of the USSR Academy of Medical Sciences (Burov Yu.V., Kampov-PoleVoy A.B., Zhukov V.N., Methodical Guidelines on Experimental/Pharmacological/Study of Preparations Suggested for Clinical Testing as Agents for Treatment and Prophylaxis of Alcoholism, Moscow, USSR Ministry of Health Publishing House, 1980, p. 21). Comparison of antialcoholic properties of lithium nicotinate was effected mainly with lithium chloride and lithium carbonate as most widely used and well studied lithium salts. However, as regards key parameters such as antiabstinent activity, the data on lithium nicotinate were compared with another novel pharmaceutical compound possessing a clearly pronounced antiabstinent activity--with lithium hydroxybutyrate. 
     The assessment of antialcoholic properties of lithium nicotinate was started for evaluation of its efficacy in the course of the formation of alcoholic dependence. 
     To this end, 160 white rats were placed for 31 days into individual cages with access to a 15% solution of ethanol in water. Every day, once a day, the quantity of ethanol consumed by the animals was measured. The data obtained during the first 10 days were used as the background. On completion of the background alcoholization the rats employed for the experiment were divided into 4 groups: control one and 3 test groups. These groups were composed of an equal number of both &#34;drinking&#34; and &#34;non-drinking&#34; rats of approximately 40 animals in each group. The animals which since the first days of alcoholization volunatrily preferred the solution of ethanol rather than water and consumed it in a quantity of not less than 2 ml/kg of the bodymass were regarded as belonging to the category of &#34;drinking&#34; rats. The rats that preferred water or consumed ethanol in supersmall doses were considered as &#34;non-drinking&#34; category of the animals. Lithium nicotinate, lithium chloride or lithium carbonate were administered to the animals of the test groups against the continued alcoholization in the doses of 10 mg/kg for the period of 14 days. The control rats were administered with injections of distilled water in the same doses and within the same time limits. The percentage of &#34;drinking&#34; rats and the quantity of alcohol consumed by them were calculated. The number of animals consuming daily not less than 2 ml/kg of ethanol during the background period was assumed as 100% and on the basis of this parameter the percentage of rats preferring alcohol during later periods was calculated. The statistic processing of the obtained data was effected by conventional methods. The effectiveness of administration of the pharmaceutical preparation was assessed by two main indicators--an increase in the percentage of &#34;non-drinking&#34; rats in each group in relation to the background and by a decrease in the quantity of alcohol consumed by each animal. 
     It has been found that lithium nicotinate inhibits the formation of addiction to alcohol. The course administration of the pharmaceutical composition according to the present invention has considerably lowered the alcoholic motivation which was revealed in a certain diminution of percentage of the &#34;drinking&#34; animals and reduction of the volume of alcohol consumed by them (see Tables 1 and 2). 
     
                                           TABLE 1__________________________________________________________________________   Time of investigation             Statistical indicators                       Number of animals (in percent preferring                       ethanol to water)__________________________________________________________________________Nos11234   Background21-st week of administration ofthe pharmaceutical   preparation weeks of administration ofthe pharmaceutical preparation1   week after cancellation              ##STR3## 100.0 4Lithium nicotinate 50.013.4&lt;0.0529.012.                       1&lt;0.00129.012.1&lt;0.001                                100.0Administered substances                                5Lithium chloride 71.012.1&gt;0.0550.013                                .4&lt;0.0550.0 13.4&lt;0.05100.0 6Lithium                                carbonate 71.012.1&lt;0.0564.012.8&gt;0.171                                .012.1&gt;0.05       100.0 7Distilled                                                  water 86.0                                                  9.3&lt;0.053.0                                                  6.8&lt;0.0593.0                                                  6.8&lt;0.05__________________________________________________________________________ 
    
     
                                           TABLE 2__________________________________________________________________________                       Average daily consumption of ethanolTime of investigation             Statistical indexes*                       in ml per 1 kg of bodymass__________________________________________________________________________Nos11234   Background21-st week of administration ofthe pharmaceutical   preparation weeks of administration ofthe pharmaceutical   preparationOne week after cancellation              ##STR4##  18.1 4Lithium nicotinate 15.1&lt;0.00112.5&lt;0.011                       3.8&lt;0.05  17.6Administered substances                                5Lithium chloride 15.7&lt;0.0515.6&lt;0.051                                6.2&gt;0.05 19.3 6Lithium carbonate                                16.1&lt;0.01 15.5&lt;0.0518.5&gt;0.05                                                   17.1 7Distilled                                                  water 17.1&gt;0.0518.5                                                  &gt;0.0518.5&gt;0.05__________________________________________________________________________ *Note: Statistical processing of the data has been performed by the Meddis method. 
    
     While in the control group 93.0±6.8% of the animals preferred ethanol to water, after a course administration of lithium nicotinate the number of &#34;drinking rats was only 29.0±12.1% /p&lt;0.01/. Consumption of alcohol by each animal in this case was reduced by 30.9% /p&lt;0.05/. Lithium chloride administered under similar conditions reduced percentage of rats-&#34;alcoholics&#34; from 93.0±6.8% to 50.0±13.4% /p&lt;0.01/ with reduction of the volume of the consumed ethanol by only 11.4% /p&lt;0.05/. In the case of administration of lithium carbonate the number of animals that preferred ethanol remained unchanged. However, the daily average consumption of alcohol was reduced by /19.7% /p&lt;0.01/. 
     The data given hereinabove demonstrate that lithium nicotinate has the ability of inhibiting formation of addiction to ethanol. The effect of this compound is substantially superior to the therapeutic activity of known salts--lithium chloride and lithium carbonate. 
     Having obtained the data on the effect of lithium nicotinate on the process of formation of addiction to alcohol we have studied the effectiveness of the preparation according to the present invention in the state of an induced alcoholic dependence and abstinent syndrome. 
     The study of therapeutic activity of lithium nicotinate in the treatment of an induced alcoholic dependence was carried out on 2 series of white rats stably consuming relatively great (50-60 ml/kg) and relatively small (20-30 ml/kg) of ethanol with 40 animals in each series (20 control and 20 test rats). The animals of both groups with a pronounced alcoholic motivation were selected according to the results of a preliminary 10-days&#39; testing. Alcoholization of the chosen animals was carried out for 3 and 8 months under conditions of a free access to a 15% solution of ethanol and water. As it is known, during these very periods stable analogs are formed in rats regarding the &#34;psychological&#34; and &#34;physical&#34; alcoholic dependence. The daily consumption of ethanol over a week prior to administration of lithium nicotinate and during two weeks of its application in the dose of 10 mg/kg was compared. Similar experiments were carried out in the case of administration of lithium chloride and lithium carbonate. The obtained data were also subjected to a statistical processing. 
     It has been found that lithium nicotinate causes a considerable lowering of ethanol consumption in both test groups during all periods of alcoholization. In 3-months&#39; rats &#34;alcoholics&#34; in the group of &#34;low-drinking&#34; animals the reduction of ethanol consumption under the influence of the preparation was by more than 2 times (10.4 ml/kg relative to 25.9 ml/kg before treatment, p&lt;0.01) as it is seen from Table 3 hereinbelow. 
     
                       TABLE 3______________________________________       Daily average consumption of etha-       nol in ml per kg of the bodymass     Statis-         1 week     tical           of in-                           2 weeks                                  One weekAdminister-     para-   Back-   jec-  of in- after can-ed compound     meters  ground  tions jections                                  cellation______________________________________Lithium   M       25.9    21.7  10.4   11.5nicotinate     P       --      &lt;0.05 &lt;0.01  &lt;0.01Lithium   M       25.3    22.2  19.9   21.6chloride  P       --      &lt;0.05 &lt;0.05  &lt;0.05Lithium   M       25.2    22.8  20.3   20.6carbonate P       --      &lt;0.05 &lt;0.01  &lt;0.05Control   M       26.4    25.1  26.0   25.1     P       --      &gt;0.05 &gt;0.05  &gt;0.05______________________________________ 
    
     Similar results were obtained in the group of &#34;low-drinking&#34; animals, as it is seen from Table 4 hereinbelow. 
     
                       TABLE 4______________________________________       Average daily consumption of etha-       nol in ml per kg of bodymass     Statis-         1 week     tical           of in-                           2 weeks                                  1 week af-Administer-     para-   Back-   jec-  of in- ter can-ed compounds     meters  ground  tions jections                                  cellation______________________________________Lithium   M       55.8    49.6  34.3   41.8nicotinate     P       --      &lt;0.05 &lt;0.01  &lt;0.01Lithium   M       46.3    41.8  37.2   39.9chloride  P       --      &lt;0.01 &lt;0.01  &lt;0.01Lithium   M       53.9    53.3  48.4   50.8carbonate P       --      &gt;0.05 &lt;0.05  &lt;0.05Control   M       51.6    56.3  56.2   56.6     P       --      &gt;0.05 &gt;0.05  &gt;0.05______________________________________ 
    
     Against the background of 8 months of alcoholization in the group of &#34;low-drinking&#34; rats lithium nicotinate, as shown in Table 5, reduced the amount of alcohol consumed over the day nearly by half. Lithium chloride administered under the same conditions and in the same doses reduce the consumption of ethanol by 19.7 and 17.4% respectively, lithium carbonate - by 19.4 and 13.4%. Equally convincing regularity was noted in the case of &#34;hard-drinking&#34; white rats, as it is shown in Table 6 hereinbelow. 
     
                       TABLE 5______________________________________       Average daily consumption of etha-       nol in ml per kg of bodymass   Statis-                          1 weekAdminister-   tical             1st week                            2 weeks of                                    aftered com- para-     Back-   of in- injec-  cancel-pounds  meters    ground  jections                            tions   lation______________________________________Lithium M         27.2    22.6   14.5    15.7nicotinate   P                 &lt;0.01  &lt;0.01   &lt;0.01Lithium M         28.8    24.7   23.8    25.6chloride   P                 &lt;0.05  &lt;0.05   &lt;0.05Lithium M         22.4    19.8   19.4    19.6carbonate   P                 &lt;0.05  &lt;0.05   &lt;0.05Control M         27.8    27.9   28.8    27.7   P         --      &gt;0.05  &gt;0.05   &gt;0.05______________________________________ 
    
     
                       TABLE 6______________________________________       Average daily consumption of       ethanol in ml per kg of body-       mass   Statis-                          1 weekAdminister-   tical             1st week                            2 week of                                    aftered com- para-     Back-   of in- injec-  cancel-pounds  meters    ground  jections                            tions   lation______________________________________Lithium M         67.0    54.4   42.6    50.4nicotinate   P                 &lt;0.01  &lt;0.01   &lt;0.01Lithium M         62.2    68.7   63.4    56.0chloride   P                 &lt;0.01  &lt;0.01   &lt;0.05Lithium M         63.2    61.1   57.9    58.3carbonate   P                 &gt;0.05  &lt;0.05   &lt;0.05Control M         63.2    62.9   65.1    63.3   P         --      &gt;0.05  &gt;0.05   &gt;0.05______________________________________ 
    
     Therefore, in experiments on white rats it has been found that under conditions of a formed alcoholic dependence lithium nicotinate exhibits pronounced antialcoholic properties. As regards the degree of deprivation, lithium nicotinate shows a higher activity than lithium chloride or lithium carbonate which corresponds to the results of experiments on investigations into the effect of lithium preparations on the formation of alcoholism. 
     The study of antiabstinent properties of lithium nicotinate was carried out on 50 white rats, 10 one-month &#34;alcoholics&#34; deprived of the access to ethanol for a week. The obtained data were compared with the results of the study of antiabstinent effects of lithium chloride and lithium carbonate and, what is most important, with lithium hydroxybutyrate having activity considerably surpassing, in this respect, those of standard lithium salts such as lithium chloride and lithium carbonate. 
     The pronouncedness of the antiabstinent activity in experiment is demonstrated by the effect of pharmaceutical compositions on the level of pathological alcoholic motivation. The level of motivation was assessed by a reduced consumption of alcohol by treated white rats--10-months &#34;alcoholics&#34; having free access to ethanol on completion of a week&#39;s period of its deprivation. 
     It has been found that the period of abstinence in rats of the control group anxiety was noted along with increased locomotive activity, tremor of limbs, refusal from taking meals. Deprivation of ethanol also resulted in an increased demand for it and upon a secondary access to a solution of ethanol the control animals consumed it by 20.9% more than prior to deprivation (87.2 ml/kg vs. 72.1 ml/kg before deprivation, p&lt;0.01). In rats treated with lithium nicotinate the above-described phenomena were revealed far weaker. The animals showed no signs of anxiety, tremor of limbs was absent, no refusal from taking meals or water was observed. On completion of the course of the antialcoholic therapy upon a secondary access to ethanol the animals consumed alcohol by 23.8% less than prior to the treatment (56.9 ml/kg vs. 74.4 ml/kg, p&lt;0.05). Lithium carbonate and lithium chloride produced a considerably weaker effect on signs of the abstinent syndrome as it is seen from Table 7 hereinbelow. 
     
                       TABLE 7______________________________________        Daily average consumption of        ethanol in ml per kg of bodymass    Statis-           One week of administrationAdminister-    tical             of the preparation aftered com-  para-     Back-   a 7-days&#39; deprivation ofpounds   meter     ground  access there to______________________________________Lithium  M         74.7    56.9nicotinate    P         --      &lt;0.01Lithium  M         77.5    64.8chloride P         --      &lt;0.05Lithium  M         70.1    59.7carbonate    P         --      &lt;0.05Lithium hyd-    M         76.2    58.5roxybutyrate    P         --      &lt;0.01Control  M         72.1    87.2    P         --      &lt;0.01______________________________________ 
    
     The effect produced by lithium hydroxybutyrate proved to be more intensive than that of lithium chloride and lithium carbonate, but still it was weaker than the effect of lithium nicotinate. In the case of using lithium hydroxybutyrate the level of consumption of alcohol reduced from 76.2 ml/kg to 58.5 ml/kg /p&lt;0.01/. In terms of percent the diminution of pathological alcoholic motivation upon administration of lithium hydroxybutyrate was equal to 23.2% (in the case of lithium nicotinate it was 23.8%). In the case of lithium hydroxybutyrate even visually such phenomena as myorelaxation, considerable lowering of locomotive activity up to a complete adynamism, retardation were observed. In the case of lithium nicotinate these symptoms were absent which was indicative of the advantages of the preparation according to the present invention. 
     The thus-obtained data have found their reflection in the results of corresponding electrophysiological studies (Frequency-amplitude interrelationsip-electroencephalogram-EEG) which were analyzed after their histographic processing. 
     The study of the effect of chronic consumption of alcohol on the bioelectrical activity of cerebral cortex of white rats has shown that a lasting alcoholization causes decrease of amplitude and increase of frequency of EEG waves. On the 6-th and 12-th weeks of voluntary consumption of alcohol EEG prevail with a low-amplitude polymorphic activity, non-uniform (as regards frequency) α-rhythms, clear-cut β-rhythms. Low bilateral paroxysms of a polymorphic character are frequently encountered. Similar data (desynchronization) but expressed to a greater extent were obtained in analysis of EEG of rats alcoholized during a 8-month&#39;s period and during abstinence. 
     The functional state of brains was also assessed by the reaction of the rhythm alteration in response to rhythmical light irritations of various frequencies. The study of the effect of chronic consumption of alcohol on the reaction of rhythm matching has shown that by the end of the 3-rd month of alcoholization, i.e. by the moment of formation of the &#34;psychological&#34; alcoholic dependence lowering of energy and reduction of the synchronization coefficient was observed. By the end of the 8th month of a voluntary consumption of ethanol and especially during the abstinence period the above-described variations of EEG were still more pronounced. 
     Administration of lithium nicotinate brings about unidirectional changes in the bioelectrical activity of brains. A slow-wave high-amplitude activity is being developed in the sight, sensomotor and audio areas of cortex of test animals. Administration of lithium nicotinate is accompanied by synchronization of all cortex potentials, increasing amplitude of all rhythms with a predominant increase of frequencies of Δ and θ ranges. It should be noted that under the influence of a course administration of lithium nicotinate not only unit waves appear but, what is most important, also group high-amplitude slow waves of the &#34;spindle&#34; type. Lithium chloride and lithium carbonate also caused synchronization of EEG upon their course administration. However, lithium nicotinate possessed a higher synchronizing effect as compared to lithium carbonate and lithium chloride. 
     The study of the effect produced by lithium nicotinate on the reaction of taking the rhythm in &#34;alcoholic&#34; rats has shown that it changes the ratio of processes of excitation and inhibition in the brain cortex: the range of assimilated frequencies is widened, the synchronization energy is increased. With nearly the same qualitative, but with a considerably smaller quantitative effect lithium chloride and lithium carbonate demonstrate their influence. In the case of using lithium nicotinate K s  and ΣA s  were certainly increased with application of relatively high (30 Hz) and relatively low (5 Hz) frequencies. In the animals treated with lithium chloride and lithium carbonate upon application of intermittent light of a low frequency the values of K 2  and ΣA s  remained unchanged. 
     Tables 8, 9 and 10 show the effect of lithium nicotinate, lithium chloride and lithium carbonate respectively on the reaction of alteration of rhythm in rats alcoholized during the periods of 3, 8 and 10 months, as well as during the period of abstinence. 
     
                       TABLE 8______________________________________                    Synchronization                    coefficient va-             Statis-                    lue (in percent)             tical  Applied             para-  frequencyTesting period      meters   5 Hz    30 HzNo.   1      2              3      4     5______________________________________1     1.     Initial data   M      99.2  98.72                           ±m  0.74  0.833     2.     6 weeks of alcohol-                       M      97.9  95.44            ization        ±m  1.55  2.085                           P 2-1  &gt;0.05 &gt;0.056     3.     12 weeks of alcohol-                       M      87.9  82.67            ization        ±m  3.76  3.488                           P 3-1  0.001 0.0019     4.     1 week of administra-                       M      98.4  94.710           tion of the pre-                       ±m  0.99  2.4811           paration       P 4-1  &gt;0.05 &gt;0.0512                          P 4-3  &lt;0.05 &lt;0.0113    5.     2 weeks of administra-                       M      98.7  95.914           tion of the pre-                       ±m  0.55  2.9315           paration       P 5-1  &gt;0.05 &gt;0.0516                          P 5-3  &lt;0.05 &lt;0.0117    6.     1 week after can-                       M      96.6  94.218           cellation of the                       ±m  2.4   2.2919           preparation    P 6-1  &gt;0.05 &gt;0.0520                          P 6-3  &lt;0.1  &lt;0.121    7.     5 months of alcohol-                       M      85.3  77.622           ization        ±m  4.05  2.6523                          P 7-1  0.001 0.00124.   8.     8 months of alcohol-                       M      80.3  76.625           ization        ±m  3.72  3.7626                          P 8-1  &lt;0.001                                    &lt;0.00127    9.     1 week of administra-                       M      91.2  86.228           tion of the    ±m  2.75  2.9729           preparation    P 9-1  &lt;0.02 &lt;0.0130                          P 9-8  &lt;0.05 &lt;0.131    10.    2 weeks of administra-                       --     95.8  94.532           tion of the prepara-                       ±m  2.48  1.9533           tion           P 10-1 &gt;0.05 0.134                          P 10-8 &lt;0.01 &lt;0.00135    11.    One week after can-                       M      94.1  93.536           cellation      ±m  2.16  1.9237                          P 11-1 &lt;0.05 &lt;0.0538                          P 11-8 &lt;0.01 &lt;0.00139    12.    10 months of alcohol-                       M      73.0  72.640           ization        ±m  3.96  4.0941                          P 12-1 &lt;0.001                                    &lt;0.00142    13.    Period of ab-  M      71.3  70.043           stinence       ±m  3.85  2.4444                          P 13-1 &lt;0.001                                    &lt;0.00145    14.    One week of ad-                       M      94.4  96.646           ministration of                       ±m  3.18  1.1947           the preparation                       P 14-1 &gt;0.05 &gt;0.0548           against the back-                       P 14-12                              &lt;0.001                                    &lt;0.00149           ground of ab-  P 14-13                              &lt;0.001                                    &lt;0.001        stinence______________________________________      Synchronization energy (in μV)      Applied frequency            5 Hz        30 HzNo.      1       6           7______________________________________1        1.      7,268.5     40,023.12                887.6       6,169.13        2,      5,053.1     31,714.34                388.1       1,915.805                &lt;0.05       &gt;0.056        3.      4,733.3     23,943.37                422.3       2,635.508                &lt;0.02       &lt;0.029        4.      6,053.0     39,287.010               405.9       933.0511               &gt;0.05       &gt;0.0512               &lt;0.05       &lt;0.00113       5.      6,960.0     40,159.514               652.30      4,738.3715               &gt;0.05       &gt;0.0516               &lt;0.01       &lt;0.0117       6.      6,560.0     35,059.518               799.3       4,256.1119               &gt;0.05       &gt;0.0520               &lt;0.1        &lt;0.0521       7.      3,808.3     23,061.722               262.27      2,307.5623               &lt;0.01       &lt;0.0224       8.      3,272.7     21,110.025               374.51      1,622.026               &lt;0.001      &lt;0.0127       9.      5,997.0     33,.686.028               288.49      2,011.0729               &gt;0.05       &gt;0.0530               &lt;0.001      &lt;0.00131       10.     7,286.0     42,116.032               515.26      2,478.2833               &gt;0.05       &gt;0.0134               &lt;0.001      &lt;0.00135       11.     6,478.0     33,952.036               542.10      4,043.5637               &gt;0.05       &gt;0.0538               &lt;0.001      &lt;0.0139       12.     3,263.8     20,950.040               500.92      1,757.9441               &gt;0.001      &lt;0.0142       13.     2,977.5     21,812.543               379.11      2,110.1344               &lt;0.001      &lt;0.0245       14.     7,22.2      52,827.846               508.74      875.9647                           &lt;0.148               &lt;0.001      &lt;0.00149               &lt;0.001      &lt;0.001______________________________________ 
    
     
                       TABLE 9______________________________________                    Synchronization             Statis-                    coefficient, %             tical  Applied             para-  frequencyTesting period      meters   5 Hz    30 HzNo.   1     2               3      4     5______________________________________1     1.    Initial data    M      99.2  98.72                           ±m  0.74  0.833     2.    6 weeks of alco-                       M      97.9  95.44           holization      ±m  1.55  2.085                           P 2-1  &gt;0.05 &gt;0.056     3.    12 weeks of al- M      87.9  82.67           coholization    ±m  3.76  3.488                           P 3-1  &lt;0.001                                    &lt;0.0019     4.    One week of ad- M      89.8  89.810          ministration of ±m  3.91  3.0411          the preparation P 4-1  &lt;0.05 &lt;0.0212                          P 4-3  &gt;0.05 &gt;0.0513    5.    2 weeks of ad-  M      90.1  93.314          ministration    ±m  4.00  3.9715          of the prepara- P 5-1  0.05  &gt;0.0516          tion            P 5-3  &gt;0.05 &lt;0.0517    6.    One week after cancel-                       M      88.6  91.418          lation of the prepa-                       ±m  4.90  1.4319          ration          P 6-1  &lt;0.05 &lt;0.0120                          P 6-3  &gt;0.05 &lt;0.0521    7.    5 months of alcoho-                       M      85.3  77.622          lization        ±M  4.05  2.6523                          P 7-1  &lt;0.001                                    &lt;0.00124    8.    8 months of alcoho-                       M      80.3  76.625          lization        ±m  3.72  3.7626                          P 8-1  &lt;0.001                                    &lt;0.00127    9.    1 week of administ-                       M      77.1  86.928          ration of the pre-                       ±m  3.41  2.5129          paration        P 9-1  &lt;0.001                                    &lt;0.00130                          P 9-8  &gt;0.05 &lt;0.0531    10.   2 weeks of admini-                       M      76.8  87.832          stration of the ±m  3.34  2.50       preparation33    10.   2 weeks of administ-                       P 10-1 &lt;0.001                                    &lt;0.00134          ration of the pre-                       P 10-8 &gt;0.05 &lt;0.05       paration35    11.   One week after can-                       M      78.1  81.636          cellation of the pre-                       ±m  4.18  2.9637          paration        P 11-1 &lt;0.001                                    &lt;0.00138                          P 11-8 &gt;0.05 &gt; 0.0539.   12.   10 months of al-                       M      73.0  72.640          coholization    ±m  3.96  4.0941                          P 12-1 &lt;0.001                                    &lt;0.00142    13.   Period of absti-                       M      71.3  70.043          nence           ±m  3.85  2.4444                          P 13-1 &lt;0.001                                    &lt;0.00145    14.   One-week admi-  M      74.0  88.046          nistration of the                       ±m  2.58  3.4847          preparation aga-                       P 14-1 &lt;0.001                                    &lt;0.0148          inst the backgro-                       P 14-12                              &gt;0.05 &lt;0.0249          und of abstinence                       P 14-13                              &gt;0.05 &lt;0.001______________________________________      Synchronization energy value, μV      Applied frequency            5 Hz        30 HzNo.     1        6           7______________________________________1       1.       7,268.5     40,023.12                887.6       6,169.13       2.       5,053.1     31,714.34                388.1       1,915.85                &lt;0.05       &gt;0.056       3.       4,733.3     23,943.37                422.3       2,635.58                &lt;0.02       &lt;0.029       4.       4,789.0     34,454.510               303.8       3,451.3411               &lt;0.02       &gt;0.0512               &gt;0.05       &lt;0.0513      5.       4,905.0     37,173.514               468.38      3,120.9515               0.0516               &gt;0.0517      6.       4,816.0     27,322.018               549.18      2,077.2319               &lt;0.05       &lt;0.0520               &gt;0.05       &gt;0.0521      7.       3,808.3     23,061.722               262.27      2,307.5623               &lt;0.01       &lt;0.0224      8.       3,272.7     21,110.025               374.51      1,622.026               &lt;0.001      &lt;0.0127      9.       3,721.0     31,681.728               331.32      2,394.3029               &lt;0.001      &gt;0.0530               &gt;0.05       &gt;0.0531      10.      3,565.0     33,612.032               331.32      3,197.7733      10.      &lt;0.001      &gt;0.0534               &gt;0.05       &gt;0.0535      11.      332.40      25,642.036               308.69      1,915.9437               &lt;0.001      &lt;0.0538               &gt;0.05       &lt;0.139      12.      3,363.8     20,950.040               500.92      1,757.9441               &lt;0.001      &lt;0.0142      13.      2,977.5     21,812.543               379.11      2,110.1344               &lt;0.001      &lt;0.0245      14.      4,744.4     45,905.646               448.10      4,095.7047               &lt;0.02       &gt;0.0548               &lt;0.05       &lt;0.00149               &lt;0.01       &lt;0.001______________________________________ 
    
     
                       TABLE 10______________________________________                    Synchronization             Statis-                    coefficient, %             tical  Applied             parame-                     frequencyTesting period      ters     5 Hz    30 HzNo.   1      2              3      4     5______________________________________1     1.     Initial data   M      99.2  98.72                           ±m  0.74  0.833     2.     6 weeks of alco-                       M      97.9  95.44            holization     ±m  1.55  2.085                           P 3-1  &gt;0.05 &gt;0.056     3.     12 weeks of alco-                       M      87.9  82.67            holization     ±m  3.76  3.488                           P 3-1  &lt;0.001                                    &lt;0.0019     4.     1 week of      M      89.5  92.210           administration of                       ±m  3.54  2.4211           the preparation                       P 4-1  &lt;0.02 &lt;0.0212                          P 4-3  &gt;0.05 &gt;0.0513    5.     2 weeks of ad- M      90.3  92.414           ministration   ±m  4.05  2.8415           of the prepa-  P 5-1  &lt;0.001                                    &lt;0.0516           ration         P 5-3  &gt;0.05 &lt;0.0517    6.     1 week after cancel-                       M      89.0  91.918           lation         ±m  3.79  3.3819                          P 6-1  &lt;0.02 &lt;0.0120                          P 6-3  &gt;0.05 &lt;0.0121    7.     5 months of alco-                       M      85.3  77.622           holization     ±M  4.05  2.6523                          P 7-1  &lt;0.001                                    &lt;0.00124    8.     8 months of al-                       M      80.3  76.625           coholization   ±m  3.72  3.7626                          P 8-1  &lt;0.001                                    &lt;0.00127    9.     1 week of admi-                       M      82.8  88.828           nistration of  ±m  2.70  2.7829           the preparation                       P 9-1  &lt;0.001                                    &lt;0.0130                          P 9-8  &gt;0.05 &lt;0.0231    10.    2 weeks of ad- M      82.9  86.232           ministration of                       ±m  3.70  2.8033           preparation    P 10-1 &lt;0.001                                    &lt;0.00134                          P 10-8 &gt;0.05 &lt;0.0535    11.    1 week after can-                       M      77.8  79.036           cellation of the                       ±m  3.98  3.6737           preparation    P 11-1 &lt;0.001                                    &lt;0.00138                          P 11-8 &gt;0.05 &gt;0.0539.   12.    10 months of alco-                       M      73.0  72.640           holization     ±m  3.96  4.0941                          P 12-1 &lt;0.001                                    &lt;0.00142    13.    Period of absti-                       M      71.3  70.043           nence          ±m  3.85  2.4444                          P 13-1 &lt;0.001                                    &lt;0.00145    14.    One-week of admi-                       M      71.3  86.646           nistration of the                       ±m  2.86  2.7447           preparation against                       P 14-1 &lt;0.001                                    &lt;0.00148           the background of                       P 14-12      &lt;0.0249           abstinence     P 14-13      &lt;0.001______________________________________      Synchronization energy value, μV      Applied frequency            5 Hz        30 HzNo.     1        6           7______________________________________1       1.       7,268.5     40,023.12                887.6       6,169.13       2.       5,053.1     31,714.34                388.1       1,915.85                &lt;0.05       &gt;0.056       3.       4,733.3     23,943.37                422.3       2,635.58                &lt;0.02       &lt;0.029       4.       4,587.0     33,906.510               385.67      2,100.5511               &lt;0.02       &gt;0.0512               &gt;0.05       &lt;0.0113      5.       5,488.0     37,742.014               324.28      2,315.1015               &lt;0.1        &gt;0.0516               &gt;0.05       0.00117      6.       4,925.5     34,542.018               326.84      2,843.1819               &lt;0.05       &gt;0.0520               &gt;0.05       0.0121      7.       3,808.3     23,061.722               262.27      2,307.5623               &lt;0.01       &lt;0.0224      8.       3,272.7     21,110.025               374.51      1,622.026               &lt;0.001      &lt;0.0127      9.       3,263.0     29,616.028               385.86      2,717.0329               &lt;0.001      &gt;0.0530               &gt;0.05       0.0231      10.      3,339.0     36,644.032               233.55      3,671.6433               &lt;0.001      &gt;0.0534               &gt;0.05       &lt;0.0135      11.      3,480.0     25,930.036               324.06      1,946.0737               &lt;0.001      &lt;0.0538               &gt;0.05       &lt;0.139      12.      3,363.8     20,950.040               500.92      1,757.9441               &lt;0.001      &lt;0.0142      13.      2,977.5     21,812.543               379.11      2,110.1344               &lt;0.001      &lt;0.0245      14.      4,310.0     42,505.046               621.01      3,199.6047               &lt;0.0248                           &lt;0.00149               &lt;0.01       &lt;0.001______________________________________ 
    
     According to modern conceptions, synchronization of an electroencephalogram, retardation of the background rhythmics appearance of &#34;spindles&#34; in combination with alteration of the range and optimum of the rhythm assimilation are the most characteristic manifestation of intensification of processes of retardation in the brains and elimination of the focus of the alcoholic dominant (Zakusov V.V. Pharmacology of Central Synapses. M., 1975, &#34;Meditsina&#34; Publishing House, p. 143). 
     The multi-purpose experiments carried out with the view to study antialcoholic properties of lithium nicotinate in combination with its advantages found in comparison with the prior art preparations--lithium chloride, lithium carbonate lithium hydroxybutyrate demonstrate that the compound according to the present invention can be widely employed as an active principle in a pharmaceutical composition. 
     Lithium nicotinate was administered to all patients following the same procedure using injections (by 1 ml of a 10% solution in an ampule) or pellets (containing 0.1 g in a pellet). The single doses were 0.1-0.2 g, daily doses--0.3-0.6 g. Some patients with insufficiently strong motives for the treatment (12 persons) with stage II of alcoholism and 21 persons with stage III of alcoholism or with a clear state of abstinent syndrome (5 persons) were injected with the preparation (1.0 ml of a 10% solution intramuscularly) for 45 days. Other patients were given lithium nicotinate in a tabletted form. The persons in the state of heavy drinking period were administered, during the first 8 days, with 0.2 g of lithium nicotinate three times a day, then with 0.1 g three times a day. The duration of the treatment course was 45 days. 
     In order to find out the potentiation effect of lithium nicotinate, the preparation in the pelletized form (by 0.1 g three times a day) was administered to 28 patients simultaneously subjected to a detoxification therapy (intravenous administration of 5.0-10.0 ml of a 25% solution of magnesia; 20.0-40.0 ml of a 40% solution of glucose; 5% of sodium ascorbate; intramuscular administration of 2.0-3.0 ml of vitamins B 1 , B 6 , B 12 ). The patients of this group suffered from alcoholism of stage III; in all of the patients psychopatholike changes of personality. Excitation prevailed in 3 persons, discontinuous drops of spirit--in 11 persons, asthenia--in 9 persons, apathism--in 4 persons. As a rule, these patients were brought for the treatment in the state of heavy drinking or of a short abstinence. The duration of the last remission was less than 4 months. The total duration of alcoholization in 19 persons was more than 19 years, in 5 persons--10- 15 years, in 3 persons--9 years. All the patients were treated under stationary conditions: 12 persons--for 4 and more times, 6 persons--3 times, 9 persons--2 times. 
     In general, lithium nicotinate was administered to 129 male persons aged from 24 to 59 years. In 69 patients alcoholism of stage II was diagnosed, in 61 persons-alcoholism of stage III. A considerable number of persons under observation were subjected to the treatment of chronic alcoholism under stationary conditions. Out of them treated in hospitals under stationary conditions for 4 and more times were 18 persons, 3 times--34 persons, 2 times--31 persons, 1 time--38 persons. For the first time 8 persons were subjected to the treatment. In these patients, as a rule, remissions were of a short duration: in 13 persons--less than 1 year, in 34 persons--less than 9 months, in 41 persons--less than 6 months, in other (33 persons)--less than 4 months. 
     The majority of the observed patients for a long time were devoted to strong beverages. 69 persons--for more than 15 years, 36 persons--for 10-15 years, 13 persons 5-10 years, 11 persons--less than 5 years. 
     Changes in personality were observed in the examined patients which extended to the degree of acuity of premorbid personality features (68 persons) and psychopathization of personality (61 persons). In the first group of patients with aggravations of premorbid personality features several types of personality changes could be found (asthenic type--41 persons, explosive type--6 persons, various kinds of the schizoid type--21 persons). Psychopatho--like changes were characterized by excitability--7 persons, periodic depressive episodes with signs of anxiety of an asthenic background--41 persons, apathism and selective aspontaniety prevailed in 13 persons. 
     In this category of patients the predominant leading syndromes were: (a) various kinds of the asthenic syndrome--astheno-depressive--40 persons, asthenohypochondriac--12 persons, asthenic--17 persons; (b) anxious-depressive syndrome--22 persons; (c) anxious-paranoid syndrome--12 persons: (d) exploxive --13 persons; (e) apathic--13 persons. A control group of patients of a similar age and nosologic origin was composed of 86 persons. The results of therapy with lithium nicotinate were compared to the results of the treatment with lithium hydroxybutyrate. Clinical characteristics of this group did not substantially differ from that of the group of patients administered with lithium nicotinate. 
     The duration of a previous abuse of alcohol in 41 persons was more than 15 years; in 27 persons--10-15 years; in 12 persons--6-10 years; less than 5 years--in 8 persons. Previously subjected to a stationary treatment for several times (4 times and more)--15 persons; 3 times--21 persons; 2 times 24 persons; 1 time--22 persons; for the first time brought to the treatment were 5 persons. 
     The duration of the last remission up to one year was in 9 persons, up to 8 months--in 19 persons, up to 6 months--in 24 persons, less than 4 months--in 29 persons. 
     In this group of patients prevailed the following persons: 
     1. With various kinds of asthenic syndrome (asthenodepressive--28 persons; astheno-hypochondriac--15 persons, asthenic--9 persons). 
     2. With anxious-depressive syndrome--13 persons. 
     3. With anxious-paranoid syndrome--6 persons. 
     4. With apathic syndrome--8 persons. 
     In this group of patients in 49 persons aggravation of premorbid personality features was observed. The most clearly pronounced symptoms corresponded to the following types: asthenic--21 persons; explosive--4 persons; to different kinds of schizoid type --24 persons. Psychopatho-like changes of personality were characterized by excitability in 7 persons; by periodic depressive episodes with signs of anxiety against the asthenic background--in 26 persons; in 8 persons apathism and aspontaneity prevailed. 
     Out of selected persons 49 patients suffered from alcoholism of stage II, 37 persons--alcoholism of III stage. 
     The treatment with lithium nicotinate and with lithium hydroxybutyrate was started from the first day of hospitalization. 
     As a rule, delivered to the stationary treatment were patients in the state of a short-time remission (66 persons out of the test group and 50 persons of the control group) or in the state of abstinence (2-3 days)--56 persons of the test group and 32 persons of the control group; 7 persons of the test group and 4 persons of the control group were delivered to the hospital in the state of a hard drinking period. 
     Furthermore, lithium nicotinate was employed for the ambulatory treatment under the conditions of an industrial enterprise. Treated were patients suffering from alcoholism of stage I (13 persons) and alcoholism of stage II (11 persons). The patients of this group were administered with lithium nicotinate in the dose of 0.1 g three times a day during 3 months. In the course of treatment normalization of emotional and vegetative disorders was noticed. During the treatment and the following 4 months no &#34;failures&#34; were observed. 
     In cases where the treatment was combined with a psychotherapeutic technique (21 persons) the preparation was first presented to the patients as an agent incompatible in the organism with alcohol which was proved by the formation of a subjective feeling of disgust to alcohol. Prior to being checked out of the hospital the patients were injected with a single dose of lithium nicotinate intravenously (3.0 ml with 15.0 ml of a 40% solution of glucose). The preparation was called &#34;torpedo&#34; and against the background of clearly manifested vegetative reactions a negative attitude to alcohol was installed. In 13 cases remissions were as long as 9 months, in 5 cases--6 months, in 3 cases--2 months. The shortest remission periods were observed in patients suffering from alcoholism of stage III. 
     The results of therapy with lithium nicotinate are presented in Tables 11, 12, 13. 
     In Table 11 generalized results of the treatment of patients with lithium nicotinate are given. In Table 12--the results for patients suffering from alcoholism of stage II. In Table 13--the data illustrating treatment of patients suffering from alcoholism in stage III. 
     
                                           TABLE 11__________________________________________________________________________         Total              Full                                 Ratio of         number              disappearance                     Improvement         Absence   successful and         of   of the considerable                               insignificant                                         of the                                              Deterio-                                                   unsuccessfulNo.   Syndrome   patients              symptoms                     stable                          unstable                               stable                                    unstable                                         effect                                              ration                                                   therapy1  2          3    4      5    6    7    8    9    10   11__________________________________________________________________________1  Anxious-depressive         22   19     1    1    1    0    0    0    20/22  Explosive  13   9      1    1    1    1    0    0    10/33  Anxious-paranoid         12   11     0    1    0    0    0    0    11/14  Apathic    13   7      2    1    2    1    0    0     9/45  Astheno-depressive         40   34     3    2    1    0    0    0    37/36  Astheno-hypohondriac         12   8      2    1    1    0    0    0    10/27  Asthenic   17   14     2    0    1    0    0    0    16/1   TOTAL: abs.         29   102    11   7    7    2    0    0    113/16   %          00   79     8.6  5.3  5.3  1,5  0    0     87,6/12.4__________________________________________________________________________ 
    
     
                                           TABLE 12__________________________________________________________________________         Total              Full                                 Ratio of         number              disappearance                     Improvement         Absence   successful and         of   of the considerable                               insignificant                                         of the                                              Deterio-                                                   unsuccessful   Syndrome   patients              symptoms                     stable                          unstable                               stable                                    unstable                                         effect                                              ration                                                   therapyNo.   1          2    3      4    5    6    7    8    9    10__________________________________________________________________________1. Anxious-depressive         13   12     1    0    0    0    0    0    13/02. Explosive  6    5      0    1    0    0    0    0    5/13. Anxious-paranoid         9    9      0    0    0    0    0    0    9/04. Astheno-hyponondric         9    6      2    1    0    0    0    0    8/15. Astheno-depressive         29   27     2    0    0    0    0    0    29/06. Asthenic   2    2      0    0    0    0    0    0    2/0__________________________________________________________________________ 
    
     
                                           TABLE 13__________________________________________________________________________         Total              Full                                 Ratio of         number              disappearance                     Improvement         Absence   successful and         of   of the considerable                               insignificant                                         of the                                              Deterio-                                                   unsuccessful   Syndrome   patients              symptoms                     stable                          unstable                               stable                                    unstable                                         effect                                              ration                                                   therapyNo.   1          2    3      4    5    6    7    8    9    10__________________________________________________________________________1. Anxious-depressive         9    7      0    1    1    0    0    0    7/21. Anxious-depressive         9    7      0    1    1    0    0    0    7/22. Explosive  7    4      1    1    1    0    0    0    5/23. Anxious-paranoid         3    2      0    1    0    1    0    0    2/14. Astheno-depressive         11   7      1    2    1    0    0    0    8/35. Astheno-hypohondriac         3    2      0    0    1    0    0    0    2/16. Asthenic   15   12     2    0    1    0    0    0    14/17. Apathic    13   7      2    1    2    1    0    0    9/4__________________________________________________________________________ 
    
     The results of the studies shown in the above Tables 11, 12 and 13 point out that the events of a full disappearance of psychopathic symptoms and of a considerable stable improvement were noted in 88% of the patients, while in 12% the therapeutic effect was of an unstable character. It was possible to attain a full disappearance of psychopathological symptoms in 79% of cases. The best results were obtained in therapy of patients suffering from alcoholism of stage II with various kinds of a depressive syndrome. 
     In psychoparmaceutical tests it is assumed that the efficiency of therapy by means of certain psychotropic preparation is determined to a great extent by an influence on so-called &#34;target-syndromes&#34;. In the treatment with lithium nicotinate emotional disorders were regarded as such symptomocomplex. It is seen from Table 11 that lithium nicotinate was most efficient in the treatment of patients with anxious-depressive and astheno-depressive syndromes. 
     In all cases the leading place in the structure of the syndrome was occupied by the proper-thymic component of the apparent syndrome: domination of disturbance of the spirit with its clear-cut lowering, psychomotoric retardation was noted, asthenic symptoms, fear and anxiety. Insomnia and loss of appetite were also noticed. Lithium nicotinate was especially effective in the case of these syndromes prevailing. The symptoms of fear, anxiety were diminished, the spirit was improved, as well as sleep and appetite. The effect of the pharmaceutical preparation according to the present invention on these emotional disturbances in the case of alcoholism makes it possible to state that lithium nicotinate has a normothymic scope of action. 
     In addition to this effect mild tranquilization and stress-protective effects of the preparation according to the present invention were also revealed. According to the data of clinical studies, administration of lithium nicotinate brings about diminution of the feeling of fear, anxiety, irritability, lacrimation, increased infatigation, weakness, retardation. The preparation improves psychic workability, does not disturb coordinate of movements and causes no myorelaxation. 
     Subject to the requirements of methodical guidelines regarding tests of novel psychotropic pharmaceutical compositions, we have carried out analysis of the dynamics of some psychopathological disorders during the treatment that has enabled an assessment of specific features of the psychotropic effect of lithium nicotinate. To this end, the severity of individual symptoms was recorded in points in 17 features-symptoms on standardized charts prior to the treatment and in the course thereof. Dynamics of the most clearly manifested psychopathological features in 129 patients suffering from alcoholism of stages II and III respectively that determined their state in general is represented in Tables 14 and 15 hereinbelow. A certain number of patients corresponds to each features, as well as the expression of the features in absolute terms (points) and in per cent relative to the initial level (during various periods of the treatment). 
     
                                           TABLE 14__________________________________________________________________________              Intensity of symptoms inpoints and in percent        Number of              prior to the                    3-rd                        8-th                            15-nd                                22-th                                    29-th                                        36-th                                            45-th                                                on completion of                                                theNo.   Symptoms  patients              treatment                    day day day day day day day treatment1  2         3     4     5   6   7   8   9   10  11  12__________________________________________________________________________ 1.   Low spirit        65    2.2   1.4 0.9 0.3 0.1 0.1 0.1 0   0 2.                100   63.6                        40.9                            13.6                                4.5 5.5 4.5 0   0 3.   Asthenization        56    1.5   1.3 0.9 0.3 0.3 0.3 0.2 0.2 0.2 4.                100   86.7                        60.0                            20.0                                20.0                                    20.0                                        13.3                                            13.3                                                13.3 5.   Anxiety   29    1.4   1.2 0.8 0.3 0.1 0.1 0.1 0.1 0.1 6.                100   85.7                        47,1                            21.4                                7.1 7.1 7.1 8.1 7.1 7.   Emotional stress        40    1.7   1.3 1.0 0.4 0.2 0.2 0.2 0.1 0.1 8.                100   76.3                        59.8                            23.5                                11.7                                    11.7                                        11.7                                            5.9 5.9 9.   Hypohondricity        37    1.5   1.3 1.1 0.9 0.5 0.5 0.3 0.3 0.310.                100   86.7                        73.3                            60.0                                33.3                                    33.3                                        20.0                                            20.0                                                20.0   Explosiveness        9     1.5   1.3 1.3 0.9 0.8 0.7 0.7 0.7 0.712.                100   86.7                        86.7                            60.0                                53.3                                    46.7                                        46.7                                            46.7                                                46.7   Apathism  8     1.3   1.0 0.6 0.3 0.3 0.3 0.1 0.1 0.114.                100   76.9                        46.2                            23.1                                23.1                                    23. 7.7 7.7 7.7   Showing-off        5     1.8   1.4 1.0 1.0 0.9 0.9 0.7 0.7 0.716.                100   77.8                        55.6                            55.6                                50.0                                    50.0                                        38.9                                            38.9                                                38.9   Reticence 7     1.4   1.2 1.0 0.6 0.4 0.4 0.2 0.2 0.218.                100   85.7                        71.4                            42.9                                28.6                                    28.6                                        14.3                                            14.3                                                14.3Astheno-vegetative disorders   Insomnia  62    1.6   1.4 1.0 0.3 0.3 0.1 0.1 0.1 0.120.                100   87.5                        62.5                            18.7                                18.7                                    6.2 6.2 6.2 6.2   Perspiration        59    1.5   1.1 0.5 0.1 0.1 0.1 0.1 0.1 0.122.                100   73.3                        33.3                            6.6 6.6 6.6 6.6 6.6 6.6   Palpitation        61    1.9   1.5 0.9 0.3 0.3 0.1 0.1 0.1 0.124.                100   78.9                        47.4                            15.8                                15.8                                    5.3 5.3 5.3 5.3   Tremor    68    1.7   1.6 1.4 0.6 0.4 0.1 0.1 0.1 0.126.                100   94.1                        82.3                            35.3                                23.5                                    5.8 5.8 5.8 5.8__________________________________________________________________________ 
    
     
                                           TABLE 15__________________________________________________________________________              Intensity of the symptom in points and in %        Number of              Before                    3-rd                        8-th                            15-nd                                22-th                                    29-th                                        36-th                                            45-th                                                OnNo.   Symptoms  patients              treatment                    day day day day day day day completion therapy1  2         3     4     5   6   7   8   9   10  11  12__________________________________________________________________________ 1.   Low spirit        54    2.2   2.4 1.0 0.9 0.3 0.3 0.1 0.1 0.1 2.                100   63.6                        45.4                            40.9                                13.6                                    4.5 4.5 4.5 4.5 3.   Asthenization        61    1.5   1.3 1.2 0.9 0.6 0.3 0.3 0.3 0.3 4.                100   86.7                        80.0                            60.0                                40.0                                    20.0                                        20.0                                            20.0                                                20.0 5.   Anxiety   44    1.4   1.2 1.0 0.8 0.5 0.3 0.3 0.3 0.1 6.                100   85.7                        71.4                            47.1                                35.7                                    21.4                                        21.4                                            21.4                                                7.1 7.   Emotional stress        58    1.7   1.3 1.0 0.8 0.6 0.4 0.2 0.2 0.2 8.                100   76.3                        58.8                            47.0                                35.3                                    23.5                                        11.7                                            11.7                                                11.7 9.   Hypohondricity        19    1.5   1.3 1.1 0.9 0.5 0.5 0.5 0.5 0.510.                100   86.7                        73.3                            60.0                                43.3                                    33.3                                        33.3                                            33.3                                                33.3   Explosiveness        20    1.9   1.5 1.5 0.9 0.9 0.9 0.9 0.8 0.812.                100   78.9                        78.9                            52.8                                47.4                                    47.4                                        47.4                                            42.4                                                42.4   Apathism  23    1.5   1.3 1.1 0.9 0.5 0.3 0.3 0.3 0.314.                100   86.7                        73.3                            60.0                                33.3                                    20.0                                        20.0                                            20.0                                                20.0   Showing-off        12    1.8   1.4 1.0 1.0 0.9 0.8 0.8 0.8 0.816.                100   77.8                        56.6                            56.6                                50.0                                    50.0                                        44.4                                            44.4                                                44.4   Reticence 12    1.4   1.2 1.0 0.6 0.4 0.4 0.4 0.4 0.418.                100   85.7                        71.4                            42.9                                28.6                                    28.6                                        28.6                                            28.8                                                28.6Astheno-vegetative disorders   Insomnia  53    1.6   1.4 1.0 0.3 0.3 0.3 0.1 0.1 0.120.                100   87.5                        62.5                            18.7                                18.7                                    18.7                                        18.7                                            8.2 8.2   Perspiration        59    1.5   1.3 1.1 0.5 0.3 0.1 0.1 0.1 0.122.                100   86.7                        73.3                            33.3                                20.0                                    6.6 6.6 6.6 6.6   Palpitation        56    1.9   1.5 0.9 0.3 0.3 0.3 0.1 0.1 0.124.                100   78.9                        47.4                            15.3                                15.8                                    15.8                                        5.3 5.3 5.3   Tremor    61    1.7   1.6 1.4 1.0 0.9 0.6 0.4 0.3 0.326.                100   94.1                        82.3                            58.8                                52.9                                    35.3                                        23.6                                            17.7                                                17.7__________________________________________________________________________ 
    
     Analysis of Tables 14 and 15 makes it possible to draw conclusions regarding the influence of the preparation according to the present invention on certain psychopathological disorders, i.e. to find out at the account of which symptoms there occurs, in general, an improvement of the patients&#39; health on the whole. Though this approach seems to be rather oversimplified, since it does not take into consideration the role of features in the structure of a particular syndrome, nevertheless it enables determination of the spectrum of the psychotropic activity of the preparation. 
     As it follows from Tables 14 and 15, lithium nicotinate provides the most effective influence at properly thymic disturbances, i.e. low spirit, without any substantial relationship with the stage of alcoholism. Lithium nicotinate produced a marked effect on depressive symptoms already since the first day in doses of 0.3 to 0.6 g a day. It should be noted that the features underwent a gradual and most pronounced reduction. Also subjected to a considerable and rapid reduction were emotional stress, anxiety, asthenization. However, the rate and degree of reduction of these disorders were slightly lower than in the case of depressive ones and depended on the structure of the syndrome in which such phenomena were noticed. As regards hypochondriac disorders of apathism, explosiveness, reticence and showing-off it should be noted that the level of the residual psychopathological symptoms was more significant. 
     It should be also noted that normathymic and tranquilization effects of lithium nicotinate are exhibited as a rule during already the first 8 days of the treatment, mainly in patients suffering from alcoholism of stage II. Continuation of the treatment results in a gradual diminution of other symptoms. The maximum effect of the preparation was observed mainly in patients with stage II of alcoholism during 15 days of therapy; later on the pace of elimination of psychopathological symptoms decreased. In patients suffering from alcoholism of stage III the preparation showed maximum effect by the 30-th day of stay in stationary hospital conditions. Later on there took place a slower diminution of the degree of intensity of psychopathological symptoms. The most resistant to the therapy with the preparation according to the present invention in patients suffering from alcoholism in stages II and III turned to be explosiveness and showing-off. 
     Analysis of the effect of lithium nicotinate on asthenovegetative disorders has made it possible to find out the degree of influence of the preparation on individual symptoms. Lithium nicotinate proved to be most effective for the removal of insomnia, tachycardia and tremor. Lithium nicotinate produced a marked influence on astheno-vegetative behaviour since the first day of treatment in doses of 0.3-0.6 g a day. It should be noted that astheno-vegetative disturbances underwent a maximum pronounced reduction during the first 3-4 days of treatment, whereafter the therapeutic effect rose at a lesser rate. This points to a certain vegetotropic effect of the preparation apparently caused by its normothymic and tranquilizing effects. Lithium nicotinate proved to be most efficient in respect of patients with vascular cerebral disturbances displayed on an rheoencephalogram through deceleration of elevation of the anacrotic phase, by reduction or increase of the dicrotic wave, its shift towards the base or summit, rounding of the summit and appearance of the venous wave. The changes observed on the part of the rheographic curve point to an increased tone or atonia of brain vessels, on the development of a venous congestion. As a result of therapeutic effect of lithium nicotinate there took place normalization of the vascular tone, improvement of brain blood circulation, reduction of phenomena of venous congestion. 
     The effect of lithium nicotinate on addiction to alcohol is further illustrated by the data of Table 16 hereinbelow. 
     
                                           TABLE 16__________________________________________________________________________          Number of patients          Before               3-rd                  8-th                     15-th                        22-th                           29-th                              36-th                                 45-th                                    On completionCharacteristics of addiction          treatment               day                  day                     day                        day                           day                              day                                 day                                    of treatment1              2    3  4  5  6  7  8  9  10__________________________________________________________________________  Reduced           52  Disappeared       77 129                     122                        129                           129                              127                                 129                                    129  Increased    129  0  0  7  0  0  2  0  0  Type of addiction changed               0  0  0  0  0  0  0  0__________________________________________________________________________ 
    
     Essential advantage is reduction of addiction to alcohol under the effect of the preparation since the 3-rd day of the treatment. The maximum effect is attained by the 8-th day. Episodic short-term (1-2 days) outbreaks of an increased addiction to alcohol should be noted under the influence of factors of the external origination in patients suffering from alcoholism in stage III. 
     The issue of duration of administration of lithium nicotinate to patients suffering from alcoholism is of a great interest. The carried out observations have shown that the most clearly pronounced effect of the preparation was revealed during the first 15 days of its administration. Later on its rate of therapeutic effect stabilized. Therefore, it is apparently possible to apply an intensive therapy with lithium nicotinate in the dose of 0.6 g a day for 15 days followed by shifting to a supporting treatment in doses of 0.3 g a day. 
     Hyperemia of the face and of the upper half of the body as well as parasthesia encountered in some cases in the treatment with lithium nicotinate can be used as a therapeutical factor in carrying-out an emotional-stressing psychotherapy of alcoholism. 
     Comparison of the data obtained in the treatment with lithium nicotinate with the data of control groups has demonstrated its higher efficiency in arresting of astheno-vegetative disorders. As compared to a conventional detoxification therapy a therapeutic effect on individual symptoms was observed by 1-2 days earlier and was more profound and stable. It is necessary, in the control group, to combine the carried out therapy with tranquilization agents and antidepressants at further stages of the treatment. 
     Therefore, the foregoing enables the following conclusions: 
     1. Clinical studies have shown that lithium nicotinate is a highly effective preparation for the treatment of alcoholism which is revealed in lowering and reduction of addiction to alcohol, normalization of individual psychopathological and personality characteristics. The preparation does not substantially exhibit any undersirable side and toxic effects. 
     2. While producing a clearly pronounced tranquilizing and normothymic effects, the preparation is especially active in arresting abstinence--softening and acceleration of reduction of astheno-vegetative disorders. 
     3. While producing a clearly pronounced stress-protective effect under conditions of an emotional overstresses and being efficient in various kinds of depressive disturbances, lithium nicotinate under laboratory conditions provides a stable negative attitude towards alcohol, while as an agent of emotional-stress therapy it also protracted the remission period, in addition to the negative relation to alcohol. 
     4. Lithium nicotinate exhibits a clearly pronounced trophic effect: it normalizes vascular tone, improves brain circulation, reduces phenomena of venous congestion simultaneously with a detoxifying effect which is apparently associated with activation of processes of oxidizing phosphorylation in the brain, improvement of provision thereof with microergs. 
     5. As a daily average dose in therapy of alcoholism 0.3-0.6 g of the preparation are advisable.