Method to prevent seasickness

The compounds of the Formula I ##STR1## (wherein R is hydrogen or halogen) and pharmaceutically acceptable acid addition salts thereof are suitable for the prophylaxis of undesired and unfavorable symptoms (e.g. perspiration, nausea, vomiting, dizziness, etc.) which occur when healthy humans or mammal animals are subjected to unusual moving (e.g. during transportation on aeroplane, or vehicles, ships, etc.)

FIELD OF THE INVENTION 
The present invention relates to a "stewardess" composition suitable for 
the prevention of disadvantageous physiological symptoms occurring during 
unusual external movement (such as transportation) of healthy humans and 
mammal animals containing a compound of the general Formula I 
##STR2## 
(wherein R stands for halogen or hydrogen) in an oral dosage form, 
optionally admixed with additives such as carriers, diluents, flavorants 
and/or coloring and aromatizing agents, and to a process for the 
preparation thereof and to the use thereof. 
BACKGROUND OF THE INVENTION 
It is known that on subjecting humans or certain mammals (e.g. dogs, cats) 
to long-lasting external moving or transportation accompanied by unusual 
or special movements (such as shaking, waving, unusual atmospheric 
conditions, great acceleration, uneven road conditions, etc.) 
characteristic undesired and unfavorable physiological symptoms occur. 
The above symptoms are generally called "sea disease" or "air sickness" 
("nausea maris", kinetosis, car-sickness, etc.). This is however no real 
disease but a physiological symptom complex which occurs with humans under 
certain conditions. The symptoms depend on the individual and his (or her) 
antecedents, training, habits and biological condition. The symptoms can 
be observed mainly portation in air or sea travel but in case of certain 
persons they occur also when travelling by motorcar, bus, train or riding, 
in an elevator, on a cable railway, etc. 
It is unnecessary to discuss the disadvantages of this condition in 
details. Persons driving in heavy traffic are very often subjected to this 
condition which is extremely disadvantageous and dangerous in cases when 
the person has to work during transport or traffic or soon afterwards. 
Thus vehicle drivers, air pilots, spacemen, astronauts, aircraft staff 
members or sportsmen, commercial travellers, businessmen, etc. who must 
exhibit high-level and concentrated intellectual or physical activity are 
badly in need of the prophylaxis of "kinetosis". This need has so far not 
been duly satisfied. 
Similarly there is a demand for the prophylaxis of undesired symptoms which 
occur on the transportation of mammal animals (e.g. hygienic 
transportation of animals, etc. after the termination of transportatio 
etc.). 
Compositions comprising scopolamine (L-6,7-epoxy-tropine-tropate) were the 
first preparations used for the propylaxis of sea-sickness. This alkaloid 
is however a strong parasympatholytic which causes visual disturbances, 
stupor, muscular weakness, dryness of mouth and the use thereof is 
dangerous. Recently attempts have made to eliminate certain undesired side 
effects of scopolamine by administering the same intradermally (Aviat, 
Space Environ. Med. 54 (II) pages 984-1000). 
The other generally used composition (Dymenhydrinate.sup.x) comprises the 
8-chloro-theophyllin salt of N,N-dimethyl-2-(diphenylmethoxy)-ethyl-amine 
as active ingredient (Daedalon.sup.R ; J. Am. Med. Assn. 160, pages 
755-760). The use of this composition involves fewer hazards but the said 
composition exhibits very unfavorable hypnotic sedative effects. Daedalon 
effects working capacity and performance during transportation or 
thereafter in an undesired manner, and moreover in certain cases makes the 
same even impossible. 
It is known furtheron that Cavinton.sup.R (comprising as active ingredient 
Vinpocetin.sup.x) decreases the affinity for kinetosis (Bodo, Hartman: 
Therapia Hungarica 27.2 (1979.)). The drawback of Cavinton.sup.R is that 
the effect is exerted only 5-7 days after administration. 
The basic factors of the neurophysiology of the kinetosis are as follows: 
The vestibular receptor, the retina and the somatosensorial receptors are 
unusually stimulated by the movement and weightlessness. The various 
structures react pathologically upon the unusual stimuli in the central 
nervous system. The reaction of the CNS is vertigo, nausea, head-ache and 
sleepiness. The reaction of the limbic system results in depression. The 
hypothalamus induces through the hypophysis an increased production of 
ADH, ACTH, GH, PRL. The vestibular cerebellum causes through the 
vegetative nervous system cold sweat, pallor, reduced stomach motility and 
cardiovascular and respiratory disorder. the vestibular cerebellum causes 
vomiting as well due to Parvicellularis Reticularis Formatio (Brain Res. 
270: 154-158.) 
The point of attack of drugs acting against kinetosis has not been 
determined exactly. Effective agents are the centrally attacking 
anticholinergic hyoscin and the adrenergic ephedrine and amphetamine. The 
activity of the phenothiazine blocking dopamine D.sub.2 receptors in the 
chemoreceptor trigger zone is very weak. Effective preventing agents are 
other antihistamines, such as dimenhydrinate, cyclizin and cinnarizene. As 
a peripherally acting agent domperidon can be mentioned. 
OBJECT OF THE INVENTION 
It is the object of the invention to provide a composition for preventing 
"sea sickness" which acts rapidly without showing any undesired side 
effects and without deteriorating psychical activity. 
DESCRIPTION OF THE INVENTION 
The present invention relates to a composition suitable for the prophylaxis 
of undesired and unfavourable physiological symptoms which occur when 
healthy humans or mammal animals are subjected to unusual external moving 
(e.g. transportation). The invention relates to the preparation and use of 
said composition as well. 
The composition according to the present invention comprises as active 
ingredient a compound of the Formula I in an oral dosage form optionally 
in admixture with suitable additives, carriers, aromatizers, flavorants 
and/or colorants. 
The compositions are prepared by simple admixture of the components. 
A particularly preferred representative of the active ingredients of the 
Formula I is the compound of the Formula IA (Selegilinum.sup.x). 
##STR3## 
The active ingredients and the processes for the preparation thereof are 
disclosed in Hungarian patent specifications Nos. 151,090, 154,655 and 
167,755. 
The use of the said compounds as psycho-stimulant, antidepressant, 
catabolic and slimming agents is described in Hungarian patents No. 
151,090. The optically active antipodes and use as MAO inhibitor are set 
forth in Hungarian Patent No. 154,655. 
The preferred dose of the compositions of the present invention is in each 
case about 10-20 mg of active ingredient of the Formula I. On 
administering the composition at a single dose of 10-20 mg every 24th hour 
an agreeable general condition can be observed and the previously 
mentioned undesired symptoms occurring due to unusual moving conditions 
(transportation) disappear during a long journey. 
The composition of the present invention can be particularly advantageously 
used by passengers and drivers of aeroplanes and other vehicles 
(motorcars, ships, air-ships, etc.). 
The composition of the present invention is highly suitable for 
administration to children subjected to unusual transportation conditions 
(aeroplane, ship). 
The single dose on children amounts to 3-5 mg, depending on the bodyweight 
for 24 hours. 
The active ingredient can be encapsulated per se optionally without any 
carrier. The desired amount of the active ingredient filled into gelatine 
capsules can be directly consumed. The present invention encompasses 
however all oral dosage forms, i.e. all forms suitable for oral 
administration. 
According to a preferred embodiment of the invention the active ingredient 
of the Formula I is finished in the form of a dragee or tablet coated by 
sugar or chocolate. 
The active ingredient is incorporated into the core. 
The composition of the present invention may be finished in the form of one 
of the following preparations: hard sweets (drops), fondant; sweets, 
nugates, marzipan optionally candied or coated by chocolate: mixed sweets, 
caramella, dragees, coated dragees and (particularly for children) chewing 
gum, syrup and dry syrup. 
The additives are determined by the appearance form of the composition. 
Thus conventional and generally used additives of sweets' industry can be 
used (e.g. saccharose and starch liquor). The compositions of the present 
invention are prepared by methods of sweets' industry known per se. The 
active ingredient of the Formula I is generally dispersed in the warm 
composition. 
As flavorants conventional additives of sweets' industry can be used, e.g. 
sacharose, dextrose, fructose, malt sugar, lactose, mannitol, sorbitol, 
saccharine, dulcitol, cyclamate, honey, sweetroot extract, coffee, tea- 
and cocoa-extract, orange-extract, extract and aroma of other fruits, 
citric acid, tartaric acid, lactic acid. 
The composition comprises conventional flavorants applicable and licensed 
in sweets' industry, e.g. tarrazine, acid-yellow, amaranth, neucoccine, 
indigo-carmine, brillant black and carbon powder (carbo medicinalis). 
The composition may also comprise preservatives and as further active 
components vitamins, particularly vitamin B.sub.6 and vitamin C. 
Compositions comprising a vitamin additive maintain the high activity 
particularly on long-lasting application. 
The above compositions may be preferably prepared by dissolving the active 
ingredient in an aqueous solution of sugar, and adding the flavorants and 
diluents. One may also proceed by adding to the mixture a binding agent 
suitable for human consumption (e.g. gum accacia) and an acceptable 
lubricating agent (e.g. stearic acid or a salt thereof). 
The active ingredients of the prophylactic compositions of the present 
invention can be prepared by known methods disclosed in Hungarian patents 
Nos. 151,090, 154,655, 187,755 and Hungarian patent application Ser. No. 
2124/84. 
The compounds of the Formula I comprise an asymmetrical carbon atom and may 
form optically active antipodes. The present invention encompasses 
compositions comprising optically active forms of the compounds of the 
Formula I. 
The preparation of the optically active compounds is described in Hungarian 
patents Nos. 154,655, 187,755 and Hungarian patent application No. 
2124/84. 
The compounds of the Formula I can be prepared preferably by reacting a 
2-phenyl-isopropyl-derivative of the Formula II 
##STR4## 
with a compound of the Formula III 
EQU B--R.sup.1 (III) 
wherein 
R.sup.1 stands for methyl or propynyl or a radical which can be transformed 
into methyl and propynyl, respectively; 
R.sup.2 stands for hydrogen or halogen or a radical which can be converted 
into halogen; 
A and B stand for radicals which on reacting with each other are capable of 
forming a bivalent radical of the Formula 
##STR5## 
or comprise the said radical; and A is attached to the carbon atom by a 
single or double bond (in the latter case it can not bear a hydrogen atom) 
if desired introducing the R.sup.2 halogen substituent into the amine of 
the Formula V 
##STR6## 
thus obtained; and if desired forming the propynyl radical in the amine of 
the Formula IV 
##STR7## 
in one or more steps; or N-methylating a compound of the Formula XIV 
##STR8## 
whereby the order of succession of the last three steps can be changed. 
The propylamine of the Formula I can be converted into an acid addition 
salt formed with a mineral acid or organic acid. 
One may also proceed by reacting an amine of the Formula VIII 
##STR9## 
wherein R.sup.4 stands for an optionally halogeno substituted and/or 
unsaturated propyl or hydrogen and 
R.sup.5 represents hydrogen or methyl with a phenyl acetone derivative of 
the Formula IX 
##STR10## 
(wherein R.sup.2 is as stated above) reducing the ketimine or oxyamine 
thus obtained and if desired converting the R.sup.4 group into propynyl 
and/or the R.sup.5 group into methyl, in any order of succession. 
One may also proceed by reacting an amine of the Formula VIII with a phenyl 
isopropyl amine of the Formula XI 
##STR11## 
(wherein X stands for halogen or a sulfonic acid ester group) and if 
desired converting the R.sup.2 group into halogen, the R.sup.4 group into 
propynyl and/or the R.sup.5 group into methyl, in any order of succession. 
According to a preferred form of realization of the process the amine of 
the Formula XII 
##STR12## 
is subjected to methylation and propynylation in any order of succession 
or condensing an amine of the Formula IV with formaldehyde and acetylene. 
Propylation may also be carried out stepwise through a halogenopropyl and 
propenyl group, respectively. Thus one may proceed by reacting the amine 
of the Formula XII with 1,2-dibromo-propene and converting the 
2-bromo-propenyl derivative thus obtained into the propynyl derivative by 
thermal treatment or reaction with a base. 
One may also proceed by reacting an amine of the Formula XIV 
##STR13## 
with a methylating agent or with formaldehyde and formic acid. The above 
mentioned methylation can be accomplished with the aid of dimethyl 
phosphate, methyl halide, dimethyl sulfate or methyl sulfuric acid. 
As an example for the introduction of the halogen atom the following method 
is mentioned: 
In a compound of the Formula VI 
##STR14## 
or of the Formula XIII 
##STR15## 
(wherein R.sup.3 is nitro, amino or diazonium) the nitro group is reduced 
to amino and the latter is transformed into diazonium-fluoro-borate and 
thus a fluorine atom is introduced in the place of R.sup.3. 
Optically active derivatives are prepared by using as starting material an 
optionally active compound of the Formula II, IV, V, VII 
##STR16## 
and of the Formula XI or XIV or subjecting a compound of the Formula I or 
VI to resolution by forming diastereomeric pair of salts by reacting with 
an optically active acid. 
The compositions of the present invention may comprise the compound of the 
Formula I in the form of a pharmaceutically acceptable acid addition salt 
thereof (e.g. hydrochloride, hydrobromide, sulfate, phosphate, acetate, 
formate, maleate, tartarate, lactate, 3,5-dinitro-benzoate, citrate, or 
(preferably) ascorbinate, oxalate, etc.). 
Further details of the present invention are to be found in the following 
Examples without limiting the scope of protection of the said Examples.

EXAMPLE 1 
Circular or angular pastilles weighing 1.3 g having the following 
composition are prepared: 
______________________________________ 
Component: Amount: 
______________________________________ 
(-)-N-methyl-N-propargyl-(2-phenyl- 
10 mg 
1-methyl)-ethyl-amine-hydrochloride 
(Selegilinum.sup.x hydrochloride) 
Saligenin 50 mg 
Carbowax 6000 40 mg 
Magnesium stearate 7 mg 
Tragacanth 58 mg 
Tartaric acid 13 mg 
Flavoring aromatics 0.004 ml 
Sugar varnish ad 1.3 g 
______________________________________ 
The basic sugar varnish and tartaric acid are thoroughly admixed, whereupon 
the active ingredient, saligenin and Carbowax dissolved in a small volume 
of alcohol is added. The mixture is thoroughly homogenized and dried. The 
dry mixture is passed through a sieve size 40, the tragacanth is added, 
the mixture is thoroughly homogenized and granulated by adding a small 
amount of syrup. The granulate is dried at 30.degree.-40.degree. C., the 
flavoring aromaties are added and the mixture is allowed to stand in a 
closed container overnight. After addition of magnesium stearate the 
mixture is pressed to pastilles in a suitable apparatus. 
EXAMPLE 2 
Sweets (drops) having the following composition are prepared: 
______________________________________ 
Component: Amount: 
______________________________________ 
Sugar 20.25 kg 
Liquid glucose 9.45 kg 
Tartaric acid 255 g 
Active ingredient 16.38 g 
Amyl-m-cresole 13.6 g 
Flavoring aromatics according to taste 
Coloring solution according to taste 
Water as required 
______________________________________ 
The sugar and liquid glucose are added to a suitable volume of water and 
the syrup of suitable consistance thus obtained is heated to boiling. To 
the hot syrup the tartaric acid and the coloring agent are added, the 
mixture is cooled to 60.degree. C. whereupon the active ingredient, 
amyl-m-cresol and the flavoring agent are added. The liquid syrup is 
carefully stirred and passed through a sugar-forming apparatus. Thus drops 
comprising 10 mg of the active ingredient are obtained. 
EXAMPLE 3 
Preparation of tablets which can be coated with a sugar varnish and are 
suitable for the manufacture of dragees. 
The following materials are used: 
______________________________________ 
Component: Amount: 
______________________________________ 
(-)-N-methyl-N-propargyl-(2-phenyl-1- 
5 kg 
methyl)-ethyl-amine-hydrochloride 
Powdered polyvidone 9 kg 
Potato starch 35 kg 
Lactose 84 kg 
96% ethanol 80 l 
Water 17 l 
______________________________________ 
The sieved components are homogenized in a mixer, granulated with aqueous 
ethanol and dried at 60.degree. C. After re-granulation the granules are 
homogenized in a fluid apparatus and the ready granules are stored in a 
container. The mixture can also be pressed to 10 mg tablets in a Fette P 
XXXI tabletting machine. 
EXAMPLE 4 
The following components are admired: 
______________________________________ 
Component: Amount: 
______________________________________ 
(-)-N-methyl-N-propargyl-[2-(4-fluoro- 
10 g 
phenyl)-1-methyl]-ethyl-amine-hydro- 
chloride 
Talc 7 g 
Magnesium stearate 5 g 
Polyvidone 20 g 
Potato starch 100 g 
Lactose 150 g 
______________________________________ 
The components are homogenized and from the mixture 1000 tablets are 
pressed in an analogous manner to the previous Examples. 
EXAMPLE 5 
Chewing gums (about 10 g) having the following compositions are prepared: 
______________________________________ 
Component: Amount: 
______________________________________ 
(.+-.)-N-methy-N-propargyl-(2-phenyl-1- 
0.02 g 
methyl)-ethyl amine hydrochloride 
Natural caoutschouc/purified/ 
2.8 g 
Dextrose 2.8 g 
Caramelle paste 0.2 g 
Powdered sugar 11.4 g 
Aroma according to taste 
______________________________________ 
The natural caoutschouc, caramelle paste and powdered sugar are kneaded and 
the solution of the active ingredient, liquid dextrose and aroma is added 
under constant stirring. The mixture is thoroughly homogenized, dried in 
the form of strips, cut to pieces weighing about 10 g and packed. 
BRIEF DESCRIPTION OF THE DRAWING 
FIGS. 1, 2 and 3 are respectively a series of three tables, designated 
Tables I, II and III. Each of the tables is a bar graph. The data in Table 
I relate to treatment of patients with Selegilinum HCl of the Formula (I) 
of the invention, the data in Table II relate to treatment with a placebo, 
and the data in Table III relate to treatment with Daedalon, an 
established compound in the prevention of motion sickness. In each table, 
the X-axis designates each of 11 patients tested and the Y-axis indicates 
the time in minutes it takes for motion sickness to occur during the test. 
The arrow at the end of each bar shows the time it takes for motion 
sickness to occur after administration of either Selegilinum HCl, the 
placebo or the Daedalon, respectively. The opposite end of each bar graph 
from the arrow shows the time it takes for motion sickness to occur 
without prior administration of any of the above. In each case motion 
sickness is induced according to the procedure set forth in Example 6, 
hereinafter. 
EXAMPLE 6 
Activity tests 
Human tests are carried out on healthy young men aged 18-23 years. The 
physical condition of the candidates is controlled by suitable basic 
tests; blood pressure, pulse, attention examination test; whereupon the 
candidates are stimulated according to the method of Coriolis (see Voenno 
Med. Zs. (1966), 9, page 59). 
The tests are carried out under usual conditions: 
a consent is obtained; 
the sufficiency of the equilibrium system is checked by ear-nose-throat and 
other examinations; 
the psychological performance is determined by means of the "Revesz Nagy" 
attention-examination test ("Psychologiai Tanacsadas a palyavalasztasban, 
Modszertani fuzetek, 11., page 5; edited by Orszagos Pedagogiai Intezet 
Budapest (1982)). 
The composition prepared according to Example 3 comprising 20 mg of 
Selegilinum.sup.x is tested and compared with placebo and Daedalon. In the 
case of each individual the period lapsed between the beginning of the 
Coriolis stimulus and the occurence of string nausea ("resistance time") 
is determined. The compositions are administered orally, to three groups: 
11 humans receive 20 mg of Selegilinum-hydrochloride; 
11 humans obtain placebo in the same dose; 
11 humans are treated with 2 Daedalon tablets (totally 100 mg). 
Two hours after the administration of the test composition the Coriolis 
stimulus is repeated and the resistance time is determined. The attention 
examination test is accomplished after the first and second Coriolis 
stimuli. The results are summarized in FIGS. 1, 2 and 3 in Table form. 
The resistance time is plotted on the vertical axis, in minutes. On the 
horizontal axis 11 humans are represented side by side. The direction of 
the arrow appearing on the Tables shows the change caused by the 
treatment: The starting point of the arrow shows the vegetative resistance 
time without influencing the organism while the end-point of the arrow 
indicates the resistance time after administration of various test 
substances (the upward arrow shows the improvement while the downward 
arrow the deterioration--in one case each). 
Table I shows the results obtained with Selegilinum-hydrochloride, Table II 
indicates those obtained with a placebo and Table III contains the results 
obtained with reference compound Daedalon. 
Evaluation of the Test 
______________________________________ 
I. Selegilinium-hydrochloride 
______________________________________ 
before: .sup.--X = 8,58 
after: .sup.--X = 14,68 
T = -2.568 
S = 3.65 S = 6.97 significant 
______________________________________ 
It can be seen that the resistance time is improved from 8.58 minutes 
(T=-2.568). Thus the improvement is significant. 
______________________________________ 
II. Placebo 
______________________________________ 
before: .sup.--X = 3.87 
after: .sup.--X = 6.25 
T = -1.64 
S = 2.33 S = 4.18 significant 
______________________________________ 
In the case of the placebo the resistance time increases from 3.87 minutes 
to 6.25 minutes (T=-1.64) and this is not significant. 
______________________________________ 
III. Daedalon 
______________________________________ 
before: .sup.--X = 4.4 
after: .sup.--X = 11.53 
T = -3.858 
S = 2.54 S = 7.3 significant 
______________________________________ 
The resistance time is increased from 4.4 minutes to 11.53 
minutes/T=-3.058/, i.e. the change is significant. 
In order to establish whether the difference between the activity of 
Seligilinum and Daedalon is significant, the following calculations are 
carried out: 
______________________________________ 
.sup.--X = 6.1 .sup.--X = 7.13 
S = 4.23409 S = 6.7743 
F = 20 
P(5%) = 2.886 
T = 0.427622 
______________________________________ 
Thus as far as the resistance time is concerned there is no significant 
difference between the said two compositions. 
The attention examination test shows no significant change between the two 
compositions. 
The subjective examinations reveal however the following results: 
placebo results in no change at all; 
under the effect of Daedalon the test persons become sleepy, tired and fall 
asleep after the test; 
under the effect of Selegilin the general condition becomes pleasant ant 
the test persons do not get sleepy. 
An unambigous explanation of the mechanism of effect of the composition 
according to the invention cannot be given yet. As according to 
observations in the literature the cerebral dopaminergic stimulation i.e. 
based on the known MAO-paralysing activity of Selegilinum does not act or 
only weakly on the kinetosis, we can give two explanations of the fact 
that the kinetosis induced by coriolis stimulus is significantly reduced 
by Selegilinum hydrochloricum: 
(1) The increase of the dopamine level in the recently discovered 
Parvicellularis Reticularis Formatio, (PCRF) results in reducing vomiting. 
This would be the first medicine of this sort. 
(2) Selegilinum hydrochloricum does not act by increasing dopamine level 
but by a different, so far unknown mechanism. 
Preparation of the active ingredients 
EXAMPLE 7 
21.92 g of N-1-phenylisopropyl-N-methyl-2-bromo-propenyl amine are 
dissolved in 320 ml of alcohol and 40 ml of a 50% aqueous potassium 
hydroxide solution are added. The mixture is refluxed for 216 hours. The 
alcohol is distilled off and to the residue water is added and the mixture 
is extracted with benzene. The benzene solution is dried over potassium 
carbonate and evaporated. The residue is distilled off in vacuo. At 
104.degree.-110.degree. C., 5 Hgmm 15 g of 
N-1-phenylisopropyl-N-methyl-propynylamine are obtained as a main 
fraction. n.sub.D.sup.20.4 =1.5229. 
The base thus obtained is converted into the hydrochloride by using 
anhydrous alcohol containing hydrogen chloride. Mp.: 
131.degree.-131.5.degree. C. (after recrystallization from a mixture of 
alcohol and ether). 
EXAMPLE 8 
7 g (0.0443 mole) of (-)-N-methyl[2-(4-fluoro-phenyl)-1-methyl]-ethyl 
amine-(.alpha.).sub.D.sup.20 =-3.44.degree. (ethanol) are dissolved in 60 
ml of acetone, whereupon 28.9 g (0.21 mole) of potassium carbonate are 
added and a 60% toluene solution of 7.56 g (0.045 mole) of propargyl 
bromide is added dropwise under stirring. The reaction mixture is stirred 
at 35.degree.-40.degree. C. for 3-4 hours, filtered, washed with acetone 
and the filtrate is evaporated. The residue is distilled off at 2 Hgmm. 2 
Hgmm. Thus 3.3 g of 
(-)-N-propynyl-[2-(4-fluoro-phenyl)-1-methyl]ethyl-amine are obtained, bp: 
120.degree.-122.degree. C., n.sub.D.sup.20 =1.5052. The melting point of 
the hydrochloride amounts to 169.degree.-171.degree. C., 
.alpha..sub.D.sup.20 =-6.2.degree. (c=2.4, ethanol); .alpha..sub.D.sup.20 
=-10.98.degree. (c=2.9, water). 
EXAMPLE 9 
10 g (0.065 mole) of 4-fluoro-phenyl-acetone and 5.3 g (0.097 mole) of 
propargyl amine are dissolved in 55 ml of 96% alcohol. After half an hour, 
1.75 g of aluminium-foil activated with mercuric chloride are added at 
60.degree. C. and the mixture is allowed to stand overnight. To the 
reaction mixture 15 ml of 40% sodium hydroxide are added and the alcohol 
is distilled off. The residue is extracted with benzene. The benzene 
solution is extracted with 10% hydrochloric acid, the aqueous hydrochloric 
acid layer is made alkaline and extracted with benzene. The benzene phase 
is dried and evaporated. The residue is subjected to distillation in 
vacuo. Thus 4.9 g of 
(.+-.)-N-propynyl-[2-(4-fluoro-phenyl)-1-methyl]-ethyl amine are obtained 
bp: 134.degree.-140.degree. C. (17 Hgmm), n.sub.D.sup.20 =1.5031, yield 
36%. 
4 g of the product thus obtained are dissolved in 25 ml of acetone, to the 
solution 4 g of potassium carbonate and 4 g of methyl iodide are added. 
The reaction mixture is refluxed for 2 hours, filtered and evaporated. The 
residue is dissolved in 10% hydrochloric acid, clarified, filtered, made 
alkaline with a 40% sodium hydroxide solution and extracted with toluene. 
The toluene solution is dried and acidified with ethanolic hydrogen 
chloride. The precipitated product is filtered and dried. Thus 3.1 g of 
(.+-.)-N-methyl-N-propynyl-[2-(4-fluoro-phenyl)-1-methyl]-ethyl 
amine-hydrochloride are obtained, mp.: 131.degree.-133.degree. C. 
EXAMPLE 10 
29.8 g of d-phenylisopropyl-N-methylamine and 14 g of propargyl aldehyde 
are dissolved in 100 ml of alcohol. 7 g of aluminium foil are cut to small 
pieces and rinsed with alcohol free of fats whereupon a solution of 30 g 
of sodium chloride and 30 ml of water is poured on the aluminum foil. The 
mixture warms up and gas evolution begins. The solution is decanted after 
6-7 minutes and the aluminum foils are washed with water. 
The aluminum thus obtained is added to the above solution under stirring 
and cooling. During the addition the reaction mixture is cooled so that 
the temperature should be between 15.degree. C. and 30.degree. C. The 
reaction mixture is stirred for 24 hours, whereupon 60 ml of a 40% sodium 
hydroxide solution are added and the mixture is stirred for a further 
hour. The two layers are separated and the aqueous phase is extracted with 
benzene three times. The benzene extracts are united with the alcoholic 
phase and evaporated. The oily and aqueous layers formed are separated and 
the aqueous phase is extracted with benzene. The benzene extracts are 
united with the oil, dried over potassium carbonate and the benzene is 
removed. The residue is distilled off at 5 Hgmm. The 
d-phenylisopropyl-N-methyl-propynylamine main fraction distils off at 5 
Hgmm, n.sub.D.sup.20.4 =1.5175; the hydrochloride melts at 131.5; 
.alpha..sub.D.sup.20 =+10.9.degree..