bluuebunny/crossref_metadata_2025 huggingface dataset:
The influence of replacement of the N-ethyl group by the cyanoethyl group on the absorption, distribution and metabolism of (±)-ethylamphetamine in man
Authors: BECKETT A H , SHENOY E V B , SALMON J A
Published: April 2011

N-2-Cyanoethylamphetamine in man was metabolized rapidly and extensively, as indicated by the analysis of the drug and its metabolite in urine, under acidic and normal conditions. A comparison with the excretion and metabolism of ethylamphetamine under comparable conditions was made. The results were assessed using an analogue computer; a simple one compartmental model sufficed to describe the excretion and metabolism of ethylamphetamine and amphetamine but the additional programming of free amphetamine was necessary for cyanoethylamphetamine because of its very rapid metabolism to amphetamine.
The properties of tablets manufactured on an automatically-controlled rotary machine
Authors: RIDGWAY K , LAZAROU C , THORPE E E
Published: April 2011

Four direct-compression bases: Celutab in the hydrous and the anhydrous form, Emcompress Special, and spray-dried lactose, have been compared with a traditional lactose granulation with respect to initial physical properties of the powder, tabletting performance and the characteristics of the tablets produced. The tablets were made on an instrumented rotary machine with feedback weight control operating to minimize time-dependent change within a batch, compression force being continuously monitored. Tensile strength by diametral crushing, porosity, disintegration time and surface indentation hardness were assessed and correlated with changes in compaction force, machine speed and tablet thickness. All materials gave wellformed tablets with no evidence of capping between 90 and 350 MN m−2, and weight variation was small except for Emcompress Special at the highest machine speed, when die filling became erratic.
Comparative investigation of inhibitors of extracerebral dopa decarboxylase in man and rats
Authors: KURUMA I , BARTHOLINI G , TISSOT R , PLETSCHER A
Published: April 2011

The decarboxylase inhibitor Ro 4–4602 [N1-(dl-seryl)-N2-(2,3,4-trihydroxybenzyl)hydrazine] in doses of 3.4–34.0 μmol/kg (1–10mg/kg) progressively enhances the increase of dopa and 3-O-methyldopa and diminishes the rise of phenolcarboxylic acids in human plasma induced by administration of l-dopa. A dose of 3.4 μmol/kg Ro 4–4602 is approximately equipotent to 17.0 μmol/kg MK 485 [β-(3,4-dihydroxyphenyl)-α-hydrazino-α-methyl-dl-propionie acid]. Ro 4–4602, combined with 2 mg/kg l-dopa, causes a higher increase of catecholamines than 20 mg/kg l-dopa alone in the striatum and probably in the hypothalamus of rat brain, whereas in the other brain areas the amine rise is equal after both treatments. MK 485 in doses equimolar to Ro 4–4602 has a less marked effect in all brain areas. Either inhibitor (10–2 μmol/kg) combined with 2 mg/kg l-dopa causes markedly less increase of catecholamines than 20 mg/kg l-dopa alone in the rat heart. Ro 4–4602, in small single doses, used at present in the treatment of Parkinson's syndrome, markedly inhibits the extracerebral decarboxylation of l-dopa in man and rats and is more potent than MK 485.
Desoxyisoprenaline: an adrenoceptor stimulating and blocking agent
Authors: MAENGWYN-DAVIES GERTRUDE D , FLEISCH JEROME H , PRUSS T P
Published: April 2011

Desoxyisoprenaline (N-isopropyldopamine, DOI), an optically inactive analogue of isoprenaline, which lacks the alcoholic -OH group, was shown to stimulate β-adrenoceptors in cat papillary muscle, rat aorta and rat trachea, in addition to causing a hypotensive effect in anaesthetized cats. DOI was also shown to stimulate α-adrenoceptors in rat aorta. Furthermore, DOI blocked both α- and β-adrenoceptors in rabbit aortic strips and β-adrenoceptors in rat trachea. These different actions indicate that DOI has both adrenoceptor stimulating and blocking properties.
Responses of blood vessels to various amines applied by microiontophoresis
Authors: STONE T W
Published: April 2011

Various amines have been applied to arterioles of the rat intestine and mesentery by microiontophoresis. Noradrenaline produced a profound constriction with a long latency and time course. This effect was prevented by phentolamine but not by propranolol. Histamine caused a partial relaxation of noradrenaline-constricted vessels, but had no apparent action on “normal” vessels. Acetylcholine and methacholine had no apparent effect on the vessels. The results are discussed in relation to previous findings. It is suggested that the effects of microiontophoretically applied amines on blood vessels may be of importance in studies of the actions of these substances in the central nervous system using this technique.
Application of orthogonal functions to the determination of naphazoline
Authors: ABDINE H , WAHBI A M , KORANY M A
Published: April 2011

A rapid method for the determination of naphazoline in antazoline- naphazoline drops is discussed. The method depends upon precipitating antazoline by a solution of sodium carbonate. Naphazoline is determined in the filtrate using (i) the modified Vierordt method and (ii) Glenn's method of orthogonal functions to correct for the unprecipitated fraction of antazoline.
The fate of [14C]disodium cromoglycate in man
Authors: WALKER S R , EVANS MARION E , RICHARDS A J , PATERSON J W
Published: April 2011

The fate of [14C]disodium cromoglycate (DSCG) has been examined in 12 asthmatic patients. Maximum plasma concentrations (mean 9.2 ng/ml) were obtained within 15 min of inhaling DSCG (20 mg) and the average plasma half-life was 81 min. Although absorption from the lung is rapid, most of the inhaled dose is swallowed. Only 2.0% of the dose was excreted in the urine, and 84% was recovered from the faeces. DSCG is poorly absorbed from the gastrointestinal tract, only 0.4 % of an oral dose (20 mg) appeared in the 24 h urine and 83 % was recovered from the faeces. Intravenous administration of DSCG resulted in approximately equal amounts (30–50% of dose) being excreted via the urine and faeces. No metabolites of DSCG were detected chromatographically.
The pharmacokinetics of inulin and urea: a comparison of the dose eliminated from a compartmental model and that eliminated in urine
Authors: BOURNE G R , BARBER H E
Published: April 2011

The distribution kinetics of inulin and urea were studied in the male rat to test the validity of a proposed compartmental model. The plasma curves could be adequately described by a biexponential function. For inulin, analysis of the results gave valid parameters in terms of an open two compartment model. These parameters did not necessarily predict the amount eliminated from the central compartment but did so under constant clearance conditions after allowance for a time lag between filtration and appearance of the drug in the collecting vessel. A triexponential fit interpreted in terms of a three compartmental model described the urea data.
Cholinesterase activity in the plasma and acid- secretory gastric mucosa of normal, castrated, and castrated oestrogen-treated male rats
Authors: OMOLE A A
Published: April 2011

Cholinesterase activity in plasma and fundic mucosa of male, normal, castrated, and castrated and oestrogen-treated rats has been measured. Castration significantly elevated cholinesterase activity in both plasma (0.02<P<0.05) and fundic mucosa (P<0.001). Castrated rats given 17β-oestradiol (120 μg, s.c. daily for 10 days) had enzyme activity in plasma and fundus not significantly different from that in normal rats.
Serum and brain concentrations of pentazocine in relation to analgesic activity in mice
Authors: PAALZOW LENNART , ARBIN ASTRID
Published: April 2011

Serum and brain concentrations of pentazocine and its metabolite, the trans-alcohol, have been studied in mice and related to analgesic activity. The concentrations were determined fluorometrically after extraction and isolation of the compounds by partition chromatography as ion pairs. The acute intravenous toxicity (LD50) of the drug was also determined. The analgesic activity was found to reside in the unchanged pentazocine since, after the initial distribution phase, the drug elicits a higher degree of analgesia in animals showing higher brain concentrations of pentazocine. Furthermore, animals which did not show an analgesic response had higher serum concentrations of the trans-alcohol in comparison with animals showing analgesic activity, indicating a relation between analgesia and the degree of metabolism. However, the relation between the analgesic response and the brain concentration during the first 20 min after intravenous injection of the drug was poor.
Effects of a bicyclic thymoleptic drug (LU 3–010) on neuroerfector function in rat isolated portal veins
Authors: HÄGGENDAL J , JOHANSSON B , JONASON J , LJUNG B
Published: April 2011

The effects of the thymoleptic drug, LU 3–010, on adrenergic transmitter release and reuptake and on effector cell function in rat isolated portal veins have been investigated. The contractile response to exogenous noradrenaline was potentiated by LU 3–010 and its concentration-effect curves after LU 3–010 10−7 g/ml were displaced to the left to a similar extent as had been found in chronically denervated preparations, indicating efficient blockade of the membrane pump mechanism. LU 3–010 10−7g/ml slightly potentiated the neurogenic response to electrical field stimulation, whereas 10−6 g/ml or more reduced the neural effector response in a concentration- dependent manner. The output of radioactive material per nerve impulse after incubation with 3H-NA was also studied. At 10−7 and 3 × 10−7 g/ml of LU 3–010 no significant change in transmitter overflow was observed. At 10−6 g/ml there was a decrease in the “fractional release”, suggesting that LU 3–010 concentrations of 10−6 g/ml or higher reduce transmitter release. Evidence is also given for a direct inhibitory effect of LU 3–010 on the smooth muscle.
Synergistic action of pyrazole on ethanol incoordination: differential metabolic and central nervous system effects
Authors: GOLDBERG L , HOLLSTEDT C , NERI A , RYDBERG U
Published: April 2011

The influence of pyrazole on ethanol-induced incoordination was measured by a modified tilting-plane technique. Pyrazole (1–77 mmol/kg; 120 mg/kg) and/or ethanol (32.6 mmol/kg; 1.5 g/kg) was given intraperitoneally to rats. Impairment of coordination was related to blood ethanol concentrations. The mean maximal impairment was significant in all conditions. For ethanol alone the maximal impairment was 8.7%, for pyrazole alone 4.8% and for ethanol + pyrazole 16.5 %. Ethanol alone induced a total impairment, assessed planimetrically, of 530 units. Pyrazole alone induced an impairment gradually increasing with time (totally 1070 units). When pyrazole was combined with ethanol, the rate of ethanol elimination was reduced by 81%, and the time it remained in the blood was prolonged from 196 ± 11 to 850 ± 16 min. The rate of disappearance was reduced from 8.05 to 1.57 μg/ml per min. The total impairment increased to 5600 units, indicating a synergistic interaction between ethanol and pyrazole, which is contrary to the normalizing effects of pyrazole on ethanol-induced metabolic changes. A “post-drug” impairment was observed one week after pyrazole, while no such effects were found after repeated administration of saline or ethanol alone in control animals. Thus, pyrazole showed acute and long-term toxic eifects.
Mouse caecum as a selective β-adrenoceptor tissue
Authors: KAUL PUSHKAR N , WHITTLE SHEILA J
Published: April 2011

The mouse isolated caecum has been found to contain β-adrenoceptors and 5-hydroxytryptamine receptors. Conditions for optimum function of the tissue in an isolated environment are described. The preparation is sturdy, lasting, economic and dependable for the screening of potential drugs, possessing agonistic or antagonistic activity on the extra-cardiac β-adrenoceptors.
Some factors affecting the absorption of paracetamol
Authors: MCGILVERAY I J , MATTOK G L
Published: April 2011

Blood concentration and urinary excretion data demonstrated that subjects who had ingested 1 g of paracetamol after fasting overnight absorbed the drug up to 5 times more rapidly but to the same extent as when they ingested the drug after a substantial high carbohydrate breakfast. Subjects who had ingested 1 g of paracetamol immediately before sleep at night excreted up to 36% less than when they took the drug at 8.30 a.m.
Sex and species differences in the biliary excretion of tartrazine and lissamine fast yellow in the rat, guinea-pig and rabbit. The influence of sex hormones on tartrazine excretion in the rat
Authors: BERTAGNI P , HIROM P C , MILLBURN P , OSIYEMI F O , SMITH R L , TURBERT H B , WILLIAMS R T
Published: April 2011

A sex difference in the biliary excretion of tartrazine, which occurs in the rat, has been found not to occur in the guinea-pig and rabbit. Male and female rats excrete 13 and 29% respectively of an intravenous dose of tartrazine (50 μmol/kg) in the bile in 3 h. The corresponding figures for male and female guinea-pigs and rabbits were 33 and 39%, and 5 and 6%, respectively. The sex difference in the rat was unrelated to any differences in renal function, for when the renal pedicles were ligated 22 and 63% of a dose was excreted in the bile of males and females respectively. Treatment of male and female rats with oestradiol and testosterone respectively influenced this sex difference in hepatic function but males were not affected by treatment with progesterone. Thus the extent of biliary excretion of tartrazine in males was increased by oestradiol pretreatment from 14 to 33% of the dose whereas testosterone pretreatment of females decreased excretion from 31 to 16% of the dose. The related dye lissamine fast yellow does not exhibit marked sex or species differences, 75–90% of a dose being excreted in the bile of males and females of all three species. Both dyes are excreted unchanged in the bile and urine of the three species.
The metabolic fate of quinine in rabbits
Authors: WATABE TADASHI , KIYONAGA KAZUE
Published: April 2011

Six metabolites of quinine were detected in the urine of rabbits given its monohydrochloride orally. Of the metabolites detected, three major ones were quantitatively separated and characterized as 2′-hydroxyquinine, 2′,3-dihydroxyquinine, and 2′,6′-dihydroxycinchonidine. No unchanged alkaloid was detected in the urine. The present results indicate that the most important reaction in the metabolism of the alkaloid in the rabbit is the formation of 2′-carbostyril derivatives.
Influence of the electron-donating properties on the psychotropic activity of phenothiazine derivatives
Authors: MERCIER M J , DUMONT P A
Published: April 2011

The electron-donating properties of substituted phenothiazine derivatives and related cyclic compounds have been determined by measuring the maximum of the lowest-energy absorption band of the corresponding charge transfer complexes with tetracyanoethylene and other electron acceptors. Phenothiazine displays a high electron-donating power. The presence and the nature of the side-chain in the 10-position do not significantly influence this property, which is much modified according to the substituent on the 2-position of the ring. The electron donor ability of phenothiazine progressively falls as the Hammet s̀ para constant of this substituent rises. The decrease parallels increase of psychotropic activity. The observations are consistent with the view that an essential part in the mechanism of psychotropic activity of the phenothiazine drugs is played by a positive radical ion.
Effect of micelle formation and the nature of the oil-phase on the distribution of a non-ionic surfactant in three- and four-component emulsions
Authors: MARLAND J S , MULLEY B A
Published: April 2011

As part of an investigation into the mechanisms responsible for the formation and stability of emulsions, the partition of the homogeneous non-ionic surfactant C8H17 [O·CH2·CH2]6OH or C8E6 (E = ethoxy) in the main two-liquid (2L) regions of the three-component systems C8E6–water–dodecane, C8E6–octanol–water and the four-component system C8E6 octanol–water–dodecane has been determined. Cmc and aggregation numbers have been obtained for the surfactant in the different phase regions. The relation of these results to emulsification in the systems is discussed.
Determination of the thermodynamics of the methyl group in solutions of drug molecules
Authors: Davis S S
Published: April 2011

The contribution of the CH3 group to the solution thermodynamics of drug molecules is dependent on whether it is attached to a ring system or is in the terminal position in an aliphatic chain. In the former case group contributions for CH3 are very similar to those found for the CH2 group. For instance, in partition, the CH3 group contribution (log Fch3) is in the range 0.65 to 0.28 (ΔG = 2.303 RT log Fch3) and is dependent on the polarity of the organic solvent. The contribution for the terminal aliphatic CH3 is not equivalent to the mid chain CH2 and a CH3 correction factor or 1.14 to 1.34 kcalmol−1 (4.77 to 5.61 kJmol−1), has been calculated from alkane solubility data and partition studies. The additivity of group contributions and the correct choice of reference state are also discussed.
Effect of additives on the kinetics of interconversion of sulphamethoxydiazine crystal forms
Authors: Ebian A R , Moustafa M A , Khalil Said A , Motawi M M
Published: April 2011

The effect of various additives on the rate of transformation of the more energetic sulphamethoxydiazine Form II to the water-stable Form III in aqueous suspension has been studied. Representative structurally related compounds, viscosity imparting agents, surfactants and colouring agents have been used to inhibit the transformation. Significant transformation retarding effects were observed in most cases. The effects vary, however, from slight retardation to almost complete inhibition of the transformation for periods of over a year (e.g. using 1 % w/v of polyvinylpyrrolidone). The effect of seeding suspensions of Form II with nuclei of Form III in the presence and absence of additives has also been examined. Accelerated stability testing is shown to be inadequate for the prediction of stability of Form II in aqueous suspension in the presence of acacia or polyvinylpyrrolidone. The use of the results in the formulation of dosage forms containing sulphamethoxydiazine is suggested.
Interference of alkanes in the gas chromatographic analysis of cannabis products
Authors: de Zeeuw R A , Wijsbeek J , Malingré Th M
Published: April 2011

Leaves of young marihuana plants (Cannabis sativa L.) were found by gas liquid chromatography to contain appreciable amounts of two long-chain alkanes, n-heptacosane and n-nonacosane. These alkanes, along with other straight chain alkanes ranging from C19 to C32 could also be detected as minor components in a variety of other marihuana and hashish samples. Depending on the polarity of the g.l.c. column used, the alkanes may have retention times similar to those of the major cannabinoids and thus interfere with qualitative and quantitative analyses of the latter. The findings indicate that g.l.c. alone cannot be used as an accurate and reliable technique for cannabinoid analysis, unless the alkanes are previously removed. However, the alkane composition may be of additional advantage in determining the origin of seized cannabis samples.
Evidence for a difference in mechanism of action between fenfluramine- and amphetamine-induced anorexia
Authors: Jespersen Sune , Scheel-Krüger J
Published: April 2011

The influence of drugs, active on 5-hydroxytryptamine (5-HT) mechanisms, has been examined on the anorexigenic activity of fenfluramine and (+)-amphetamine in rats trained to consume their daily food ration during 6 h. Chlorimipramine, which inhibits the re-uptake mechanisms in central 5-HT neurons, and the 5-HT blocking drugs methergoline and methysergide were used. Fenfluramine, 7.5 mg kg−1, and amphetamine, 2.5 mg kg−1, given 1/2 h before feeding reduced the food intake during the following 2 h to approximately 40% compared with control days. Pretreatment with methergoline in the optimal dose (1 mg kg−1) produced only a weak but significant antagonism to amphetamine anorexia, whereas the fenfluramine anorexia was strongly antagonized by methergoline in all doses tested (0.3, 1 and 3 mg kg−1). Methysergide (0.1, 0.3, 1 and 3 mg kg−1) showed no significant antagonism against amphetamine or fenfluramine anorexia. Chlorimipramine produced a strong antagonistic effect to the fenfluramine anorexia, but showed no antagonism against amphetamine. In contrast the highest dose of chlorimipramine (20 mg kg−1) potentiated amphetamine anorexia. The present results together with other evidence discussed support the conclusion that 5-HT mechanisms are involved in fenfluramine anorexia, whereas amphetamine anorexia seems mainly correlated with catecholamine dependent mechanisms.
Drug-induced changes of striatal cholinergic and dopaminergic functions in rats with spreading depression
Authors: Keller H H , Bartholini G , Pletscher A
Published: April 2011

In rats with reversible, functional inactivation of one striatum by spreading depression (SD), dopaminergic stimulation of the intact striatum by Ro 4–4602 plus L-dopa, pargyline plus Ro 4–1284 as well as apomorphine or methamphetamine caused body torsion and rotational movements towards the side of SD. Neuroleptic drugs lead to contralateral body torsion. The apomorphine-induced functional changes were antagonized by the acetylcholine-like drugs arecoline and oxotremorine, but not by nicotine. Atropine, but not methylatropine, blocked the action of arecoline. It is concluded that in the regulation of muscle tone and locomotor activity, a cholinergic system (probably with muscarinic cholinoceptive sites) and a dopaminergic system in the striatum, antagonistic to each other, are involved.
Some actions of 4,17a-dimethyl-4,17a-diaza-D-homo-5α-androstane dimethiodide (HS-342), a new neuromuscular blocking drug
Authors: Marshall I G , Paul Dharami , Singh Harkishan
Published: April 2011

The effects of the newly-synthesized bisquaternary steroid 4,17a-dimethyl-4,17a-diaza-D-homo-5α-androstane dimethiodide (HS-342) have been investigated on the rat isolated phrenic nerve-hemidiaphragm, chick biventer cervicis and intact cat tibialis anterior muscle preparations, on the guinea-pig isolated ileum and on the rat isolated vas deferens preparations. The anticholinesterase activity of HS-342 was also measured. In the skeletal muscle preparations HS-342 exhibited properties of a post-junctionally active neuromuscular blocking agent of the non-depolarizing class. In the anaesthetized cat HS-342 exhibited approximately equal activity to that of tubocurarine, but its duration of action was about one-third of that of tubocurarine. HS-342 exhibited low anticholinesterase activity, low muscarinic blocking activity and apparently had no effect on the adrenergic neuroeffector junction studied.
Pharmacology of diferuloyl methane (curcumin), a non-steroidal anti-inflammatory agent
Authors: Srimal R C , Dhawan B N
Published: April 2011

Some pharmacological actions of curcumin (diferuloyl methane) have been examined in rats, mice and cats. The compound possesses significant anti-inflammatory activity in acute as well as in chronic models of inflammation. It is as potent as phenylbutazone in the carrageenan oedema test but only half as potent in chronic tests. Curcumin possesses a much lower ulcerogenic index than phenylbutazone. It prevents the inflammation induced increase in SGOT and SGPT levels. It lacks analgesic and antipyretic activity. It has no other significant pharmacological effects. The oral LD50 in mice is more than 2ṁ0 g kg−1.
Micromethod for the determination of bupivacaine in maternal and foetal blood during obstetric analgesia
Authors: Berlin Anita , Persson Bengt-Arne , Belfrage Patrick
Published: April 2011

A method for the determination of bupivacaine in maternal and foetal blood during obstetric analgesia is described. The drug and the internal standard, 1-pentyl-2-(2,6-xylylcarbamoyl)-piperidine, are initially extracted into methylene chloride. Perchloric acid is added to retain bupivacaine and the standard as Perchlorates in the organic phase accomplishing a selective separation from less hydrophobic amines. Bupivacaine and the standard are then re-extracted into sulphuric acid, followed by a purification with methylene chloride. The aqueous extract is finally made alkaline and the compounds extracted into 10 μl methylene chloride. This extract is analysed by gas chromatography using a 3% OV-17 column. The standard deviation of the method at therapeutic concentrations is about 10% and the lowest level which can be determined with reasonable accuracy is 15 ng ml−1.
Release of dipicolinic acid and calcium and activation of Bacillus stearothermophilus spores as a function of time, temperature and pH
Authors: Brown M R W , Melling J
Published: April 2011

The kinetics of release of dipicolinic acid and calcium from Bacillus stearothermophilus spores and the rate of increase of colony count have been shown to be determined by conditions of time, temperature and pH. The apparent activation energies for release of dipicolinic acid, calcium and colony count increase were similar. The results support the hypothesis that breaking of dormancy involves a rupture of dipicolinic acid bonds and that the nature of these bonds rather than the dipicolinic acid content determines dormancy and resistance.
The ganglion blocking and vagolytic actions of three short-acting neuromuscular blocking drugs in the cat
Authors: Marshall I G
Published: April 2011

Three recently-introduced short-acting neuromuscular blocking drugs with non-depolarizing mechanisms of action, stercuronium, dacuronium and AH8165 (1,1′-azobis [3-methyl-2-phenyl-1H-imidazo (1, 2a) pyridinium] dibromide) have been tested in the anaesthetized cat on the responses of the nictitating membrane to stimulation of the cervical nerve, and of the heart to vagal stimulation. The effects of the three drugs at the superior cervical ganglion and at the cardiac neuroeffector junction have been compared with their neuromuscular blocking effects. At doses lower than those required to block neuromuscular transmission all three compounds possessed a selective atropine-like action at the cardiac vagus neuroeffector junction in that they inhibited the bradycardia produced by vagal stimulation and by acetyl-β-methylcholine, whilst the depressor action of acetyl-β-methylcholine was unaffected. The ratios of the doses of the drugs to block the responses of the preganglionically-stimulated nictitating membrane and of the tibialis anterior muscle were 16ṁ7 for stercuronium, 8ṁ5 for dacuronium and 3ṁ8 for AH8165. The greater ganglion-blocking activity of AH8165 was reflected in the depressor action of the compound, whereas the weak ganglion-blocking actions of stercuronium and dacuronium were insufficient to mask the tachycardia and pressor effect caused by their blocking action on the cardiac vagus neuroeffector junction.
The recovery of bacteria from white soft paraffin
Authors: Allwood M C , Hambleton R
Published: April 2011

Methods have been investigated for isolating and enumerating, by a membrane filtration technique, E. coli inoculated into white soft paraffin. Of three solvents used to prepare the ointment base for filtration, the best recovery (54%) was obtained with light liquid paraffin. Superior recovery levels (ca 75%) were obtained by homogenizing the ointment base with a Tween 80/peptone water mixture. Recovery levels were greatly affected by the weight of ointment base taken but the Tween 80/peptone water system permitted the estimation of the contamination in up to 0ṁ25 g of white soft paraffin.
Total and free-plasma tryptophan concentrations in rheumatoid disease
Authors: Aylward Mansel , Maddock Jeffrey
Published: April 2011

It has been proposed (McArthur, Dawkins & others, 1971) that human connective tissue diseases may arise from modifications in the binding characteristics of the plasma proteins. McArthur, Smith & Freeman (1972) presented evidence that human serum contains a substance that possesses anti-inflammatory activity and is bound to circulating proteins. Furthermore, it has been suggested that, in patients with active rheumatoid arthritis, the anti-inflammatory substance is bound to an abnormal extent to the plasma proteins and that the clinically useful antirheumatic drugs act by re-establishing the bound: free ratio to that in the normal subject (Smith & Dawkins, 1971). There is evidence that the behaviour of L-tryptophan mimics that of the hypothetical substance which protects susceptible tissues against chronic inflammatory insults. All the clinically useful antirheumatic agents were found to displace L-tryptophan from human plasma in vitro (McArthur, Dawkins & Smith, 1971) but not so other drugs which bind to plasma proteins to an equivalent extent but have no demonstrable antirheumatic effects (Smith, Dawkins & McArthur, 1971). In patients with rheumatoid arthritis receiving drug therapy the percentage of L-tryptophan bound to plasma proteins is significantly reduced but increases when drug administration is stopped (McArthur, Dawkins & others, 1971).
A note on the solubilization of preservative mixtures by cetomacrogol
Authors: Crooks M J , Brown K F
Published: April 2011

Preliminary data are reported for the solubilization of several pairs of preservatives by the non-ionic surfactant cetomacrogol. In all cases the addition of a second preservative altered the equilibrium solubility of the first to an extent which depended on the particular co-solute and the concentration added.
Use of substituent constants in structure-activity relations and the importance of the choice of standard state
Authors: Davis Stanley S
Published: April 2011

The value of the hydrophobic group substituent constant (π), calculated from logarithms of partition coefficients, is normally independent of the choice of the standard state used for the partition studies. However, in some cases e.g. when a partition coefficient for the intact molecule is taken as being equivalent to a π value, the choice of standard state is of utmost importance. It is suggested that π values may be additive on the mole fraction (thermodynamic partition coefficient) scale and not the molar scale as has been previously assumed. Consequently, some published π values may be in error.
The excitation of neurons by noradrenaline
Authors: Bevan P , Bradshaw C M , Roberts M H T , Szabadi E
Published: April 2011

Responses of single cortical neurons to microelectrophoretically applied noradrenaline at pH 3.1 and 5.0 and to hydrogen ions were compared in the halothane-anaesthetized cat. Of 16 neurons sensitive to noradrenaline, 13 were excited and 3 were depressed by noradrenaline at both pH values, whereas hydrogen ions released from an HCl solution did not affect the firing rate. Dose-response studies showed that noradrenaline at pH 3.1 was more potent than at pH 5.0. It is concluded that excitatory responses to noradrenaline are not artifacts and that the adjustment of the pH of noradrenaline solutions with NaOH should be avoided.
Gas chromatographic determination of ethosuximide and phensuximide in plasma and urine of man
Authors: van der Kleijn Eppo , Collste Per , Norlander Björn , Agurell Stig , Sjöqvist Folke
Published: April 2011

Ethosuximide and phensuximide in plasma and urine can be assayed to a concentration of 2–5 μg ml−1 by a rapid and specific gas chromatographic assay. The method can be used to monitor plasma concentrations in patients with petit mal treated with these drugs alone or in combination with other antiepileptic drugs. The steady-state plasma concentrations of ethosuximide in children given 10–45 mg kg−1 day−1 varied between 10 and 150 μg ml−1 indicating marked interindividual differences in pharmacokinetics.
The identification, properties and analysis of N-hydroxyamphetamine—a metabolite of amphetamine
Authors: Beckett A H , Al-Sarraj S
Published: April 2011

N-Hydroxyamphetamine (Ib) can be extracted from aqueous solutions at neutral pH, but is readily decomposed into syn- and anti-phenylacetone oximes (II) at alkaline pH values. Gas chromatography of Ib is possible, provided the compound does not come into contact with heated metal surfaces. In aqueous media the hydroxylamine can be determined (1) by extraction from the medium with ether and analysis of the ethereal solution by g.l.c.; (2) by separation of the compound on a thin-layer then oxidation of the hydroxylamine spot with ammoniacal silver nitrate to give phenylacetone oximes which may then be determined by g.l.c.; (3) by reduction with lithium aluminium hydride to amphetamine (Ia) followed by g.l.c.; (4) conversion to phenylacetone oximes by shaking at pH 12 in air, extraction of the oximes, followed by g.l.c.; (5) Alternatively, N-hydroxyamphetamine can be determined directly in aqueous solution by polarography provided the measurement is made immediately after the supporting electrolyte, sulphite/NaOH, has been added.
The central and peripheral activities of anti-acetylcholine drugs. Some concepts of practical relevance
Authors: Inch T D , Green D M , Thompson Pamela B J
Published: April 2011

Five procedures have been used to compare the pharmacological effects and time-activity profiles of anti-acetylcholine drugs in the central and peripheral nervous system (ens, pns). In particular, the potencies of optically pure enantiomers of anti-acetylcholine drugs which contain an asymmetric centre have been determined. The following four observations are made which are of relevance to all studies of anti-acetylcholine drugs. (1) Times to onset of activity of anti-acetylcholine drugs in three in vivo tests and the duration of action in one in vivo test are shown to increase as affinity constants, determined in vitro, increase. (2) Below a dose of ca 0.03 μmol kg−1no anti-acetylcholine drug produces maximum mydriatic effects and all anti-acetylcholine drugs which have log affinity constant values >9.49 produce maximal effects at approximately this dose. (3) The receptor with which anti-acetylcholine drugs interact is essentially the same in the eye, salivary gland and ens of the mouse, the guinea-pig ileum, and in the cat ens. (4) For any anti-acetylcholine drug the time to onset of effects in the ens is similar to the time of onset of effects in the pns and appears to depend on the affinity constant rather than on the partition properties of the drug. The practical and theoretical significance of these and other observations are discussed.
The effects of thyroid hormones on monoamine oxidase in the rat heart
Authors: Lyles G A , Callingham B A
Published: April 2011

The administration of thyroxine to young male rats produced an increase in the specific activity of their cardiac monoamine oxidase (MAO). A reduction in the circulating concentrations of thyroid hormones, brought about by 2-thiouracil, led to a decrease. The relative change in activity produced was greater with tyramine than with benzylamine as substrate. By following the time-course of the return of enzyme activity, with tyramine as substrate, after a single injection of pargyline in vivo, it was concluded that both excess and lack of thyroid hormones cause their effects on MAO activity by changing the rate of synthesis of the enzyme and not its degradation rate constant. The degradation rate constant did change with the age of the animal. The MAO activity, which increased towards tyramine as substrate in hyperthyroid rat hearts, behaved in the same way as that of controls to heat treatment, irreversible inhibition by pargyline or by clorgyline and also in Km determinations. The pattern for benzylamine oxidation was similar, except for the effect of the inhibitor clorgyline which shifted the plateau region of the double sigmoid inhibition curve significantly using enzyme from hyperthyroid rat hearts. The plateau region was also shown to be affected by the age of the animal. The possibility is discussed that the increased cardiac MAO activity produced by thyroid hormones and by the growth of the animal is mediated by that form of the enzyme primarily responsible for the oxidation of tyramine. Mixed substrate experiments suggested that tyramine oxidation could be inhibited competitively by benzylamine.
Phenylalanine, brain phenethylamine and motor activity in the rat
Authors: Snodgrass S Robert
Published: April 2011

Varying doses of L-phenylalanine were administered intraperitoneally to rats and motor activity determined by means of photocells in an activity cage. Control rats, and rats whose brain catecholamines were depleted by reserpine, α-methyl-p-tyrosine, or intraventricular 6-hydroxydopamine showed a decrease or no change in motor activity following phenylalanine injections. Injections of the decarboxylase inhibitor, Ro 4–4602, failed to alter the effect of phenylalanine. After injections of [3 H]phenylalanine, [3 H] β-phenethylamine accounted for less than 5 % of brain tritium and radioactivity associated with this amine declined rapidly with time. The proportion of brain radioactivity due to β-phenethylamine was increased by the monoamine oxidase inhibitor, pargyline, and was not affected by the peripheral decarboxylase inhibitor Ro 4–4602. When Ro 4–4602 and pargyline were given together, the increase in radioactive phenethylamine produced by pargyline was prevented, suggesting that a significant proportion of brain phenethylamine may be synthesized in the periphery and can enter brain if monoamine oxidase is inhibited.
Disulphide cross-linking of thiolated α-chymotrypsin to form macromolecules
Authors: Mahbouba M , Pugh W J , Smith H J
Published: April 2011

Thiolation of α-chymotrypsin with N-acetyl homocysteine thiolactone (AHTL) occurs in the presence of Ag+ and imidazole with the introduction of 4–5·5 SH groups per mole. Oxidation of the thiolated enzyme with ferricyanide gave a macromolecule consisting of thiolated enzyme residues cross-linked through intermolecular disulphide bonds. The number of residues linked in this manner varied with each batch of thiolated enzyme but was within the range 16–44 residues. The light scattering data indicated that the macromolecule was rod-shaped.
The uptake of digoxin and digitoxin by some antacids
Authors: Khalil Saleh A H
Published: April 2011

The adsorption of digoxin and digitoxin by some antacids has been investigated. Magnesium trisilicate showed the highest adsorptive effect, the extent of adsorption being up to 99 % for the two glycosides. The calculated values of monolayer adsorption were 0·93 and 1·36 mg g-1 for digoxin and digitoxin respectively. At 37° only partial elution of adsorbed glycosides occurred in 0·2N HCl due to re-adsorption on the hydrated silica gel formed. Antacid preparations containing magnesium trisilicate adsorbed digoxin from a paediatric elixir to the extent of about 95%. Dissolution of digoxin tablets was similarly affected since almost complete suppression of dissolution occurred in the presence of 0·5 g magnesium trisilicate per 0·25 mg digoxin tablet. The effect of antacids, when concurrently administered with oral digoxin, on the bioavailability of the drug, is discussed.
The effect of emetine on myocardial catecholamine metabolism
Authors: Miletich D J , Ivankovic A D , Albrecht R F , Toyooka E T
Published: April 2011

The effects of emetine on the uptake and release of noradrenaline from the isolated, perfused, rat heart and on the in vivo myocardial retention of noradrenaline have been studied. Hearts were removed from animals under light ether anaesthesia, transferred to a modified Langendorff perfusing apparatus and perfused with Krebs-Ringer bicarbonate solution at a rate of 5 ml min−1. The effect of emetine on the uptake of noradrenaline was determined by perfusing hearts for a period of 6 min with perfusate containing various concentrations of emetine and 100 ng ml−1 of [14C]noradrenaline (14C-NA). After 6 min, the emetine-treated hearts contained less (±)−14C-NA than control hearts. The degree of reduction increased with increasing concentrations of emetine. The release of noradrenaline was determined after first perfusing hearts with 14C-NA followed by perfusion with solution containing emetine (0–01 mg ml−1) but free of labelled noradrenaline for periods of 10, 20 and 60 min. It was found that by 60 min emetine significantly decreased myocardial 14C-NA. In the intact animal myocardial concentrations of 14C-NA were reduced 90 min after intravenous 14C-NA, followed immediately by intraperitoneal emetine (1 mg kg−1). These results suggest that the cardiac arrhythmia and irritability seen after emetine treatment in man may be partly due to alterations in catecholamine metabolism.
Effect of chronic intoxication with (+)-amphetamine on its concentration in liver and brain and on [14C] leucine incorporation into microsomal and cytoplasmic proteins of rat liver
Authors: Magour S , Coper H , Fähndrich Ch
Published: April 2011

Rats were treated with increasing concentrations of (+)-amphetamine sulphate in drinking water for 90 days. The ingested dose of amphetamine was found to increase from 16 mg kg−1 on the first day up to 90 mg kg−1 on the 32nd day of treatment. The rats were maintained on the highest dose regime for a further 58 days without any deaths, which showed that tolerance to the overall toxicity of the drug developed. The concentrations of [3H]amphetamine in liver and brain of chronically treated rats were significantly higher than those of controls. Chronic treatment with amphetamine significantly reduced body and liver weight of rats, but did not influence the relative liver to body weight. A marked inhibition of [14C]leucine incorporation into liver microsomal and cytoplasmic proteins was observed after 90 days of treatment with amphetamine. The relation between inhibition of microsomal protein synthesis and the increase of amphetamine concentrations in liver and brain is discussed.
Role of the central autonomic nervous system in the hypotension and bradycardia induced by (-)-Δ9-trans-tetrahydrocannabinol
Authors: Vollmer R R , Cavero I , Ertel R J , Solomon T A , Buckley J P
Published: April 2011

(-)-Δ9-trans-Tetrahydrocannabinol (Δ9-THC), when given intravenously (2 mg kg−1) to cats, produced marked decreases in blood pressure and heart rate which developed gradually and were of prolonged duration. Cervical spinal transection (C1-C2) abolished these effects whereas surgical removal of neurogenic tone to the myocardium selectively eliminated the bradycardia. Bilateral vagotomy alone did not modify the action of Δ9-THC upon heart rate or blood pressure. Recordings of spontaneous sympathetic outflow in the inferior cardiac nerve indicated a rapid reduction in neural discharge rate after Δ9-THC administration. These observations support the hypothesis that Δ9-THC produces a cardiodecellerator and hypotensive effect by acting at some level within the sympathetic nervous system. Experiments conducted to investigate transmission in the superior cervical and stellate ganglia demonstrated that Δ9-THC did not alter ganglionic function. Also, responses to intravenous isoprenaline and noradrenaline were unchanged which suggested that Δ9-THC did not interact with α- or β- adrenoceptors. The possible action of Δ9-THC on central sympathetic structures was investigated by perfusion of Δ9-THC into the lateral cerebral ventricle. Δ9-THC so administered produced a significant reduction in heart rate without a substantial lowering of blood pressure. Tritiated or 14C-Δ9-THC perfused into the lateral ventricle demonstrated that the amount of radioactive compound passing into the peripheral circulation was insignificant and could not account for the decrease in heart rate. The current data are in agreement with the proposal that Δ9-THC produces cardiovascular alterations by an action on the central nervous system which results in a decrease in sympathetic tone.
Infrared spectroscopy using attenuated total reflection
Authors: Kang I P S , Kendall C E , Lee R W
Published: April 2011

An ATR method is given for the examination of pharmaceuticals in the solid state as a layer of crystals on adhesive tape. Representative spectra are chosen to compare with, and to indicate advantages over, disc and mull techniques. Application of the method to pharmaceutical formulations is illustrated by the direct spectral identification of amodiaquine hydrochloride in tablet formulation.
Growth and sporulation characteristics of Bacillus megaterium under different conditions of nutrient limitation
Authors: Brown M R W , Hodges N A
Published: April 2011

The quantitative nutritional requirements to achieve specific cell densities have been studied for B. megaterium. Growth of batch cultures was separately limited by depletion of glucose, ammonium, sulphate, potassium, phosphate, manganese and magnesium. Maximum population density (E420) for graded concentrations of each limiting nutrient was plotted against nutrient concentration and a linear plot was obtained below a critical concentration. Under conditions of magnesium depletion, two phases of growth occurred separated by a plateau. Proposals are made for the use of these cultures in drug resistance studies. Sporulation occurred in all cultures except those limited by potassium, manganese or magnesium. Spores were produced in magnesium-limited cultures provided that glucose was simultaneously depleted. Spores produced under different conditions of nutrient depletion varied in germination characteristics, heat resistance and spore volume.
Competitive interaction of preservative mixtures with cetomacrogol
Authors: Crooks M J , Brown K F
Published: April 2011

The binding of various preservatives, alone and in pairs, to cetomacrogol has been investigated. Data for the compounds alone indicate that all preservatives combined with two distinct classes of sites in the cetomacrogol micelle. The data were expressed in the form of Scatchard plots and the association constant and number of sites in each class were calculated. All combinations of preservatives were shown to exhibit substantial competition resulting in diminished binding, however the nature of the competitive process is not the same in all cases. Chloroxylenol and dichloroxylenol do not compete significantly with methyl paraben in the first class of sites, but substantial competition was observed in the second class. In contrast, methyl paraben and propyl paraben compete strongly for the first class of sites. Competition with these compounds also occurred in the second class of sites but this was coincident with a large increase in the number of secondary binding sites which tended to increase binding.
Adsorption of atropine and hyoscine on magnesium trisilicate
Authors: El-Masry Sawsan , Khalil Saleh A H
Published: April 2011

The adsorption of atropine and hyoscine by magnesium trisilicate has been studied. At relatively low initial concentrations the adsorption data were shown to fit a Langmuir plot and values for monolayer adsorption were 14·9 and 3·8 mg g−1 for atropine and hyoscine respectively. The extent of adsorption was increased at higher initial concentrations due to multilayer formation. The presence of either sodium citrate or sodium phosphate suppressed the adsorption. Elution of the adsorbed alkaloid was dependent on the pH of medium used and followed the order: 0·05n HCl (pH 1·5) >0·01n HCl (pH 2·1) > water (pH 5·5). Due to the dissolution of magnesium trisilicate, at 37° in 0·05n HCl, neither the rate of acid uptake nor the acid absorption test of the adsorbent were significantly reduced by the adsorption of either alkaloid. In the B.P.C. mixture of magnesium trisilicate and belladonna, almost complete adsorption of hyoscyamine occurred and the elution of the adsorbed alkaloid depended on the level of hydrochloric acid in the elution medium used.