bluuebunny/crossref_metadata_2025 huggingface dataset:
An analysis of the action of drugs on the circular muscle strips from the caecum of the guinea-pig
Authors: AKUBUE P I
Published: April 2011

The taenia-free circular muscle strips of the caecum of the guinea-pig contracted to acetylcholine or histamine. 5-Hydroxytryptamine produced small contractile responses but high concentrations (40 μg/ml or more) induced relaxation. The contractions to 5-hydroxytryptamine were enhanced by the organophosphorus anticholinesterase drug mipafox. The responses to nicotine were always relaxations but contractions were obtained after incubating the preparation with mipafox. Hence circular muscle strips treated with mipafox were used to investigate the mechanism of contractions to all the drugs. The site of action of acetylcholine or histamine was located on the smooth muscle cells because the responses were not blocked by pentolinium, dimethylphenylpiperazinium, procaine or cocaine. Hyoscine blocked the responses to acetylcholine but left those to histamine unchanged. The contractions to nicotine were blocked by hyoscine, local anaesthetics or ganglion blocking drugs. Nicotine is thought to activate cholinergic ganglion cells. 5-Hydroxytryptamine produced contractions which were potentiated by mipafox, blocked by hyoscine and almost abolished by local anaesthetics. The responses were not modified by pentolinium but were reduced by dimethylphenylpiperazinium at a concentration which did not block the responses to acetylcholine or histamine. It is concluded that the action of 5-hydroxytryptamine was wholly indirect, on nervous tissues, part of which was located on cholinergic ganglion cells.
Simultaneous polarographic determination of 1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole, 1-(2-hydroxyethyl)-2-methyl-4-nitroimidazole and 2-methyl-5-nitroimidazole
Authors: DUMANOVIĆ D , VOLKE J , VAJGAND V
Published: April 2011

A method for the simultaneous quantitative polarographic determination of the three components in reaction mixtures has been proposed. The analysis is based on a separation of the half-wave potentials in strongly alkaline base solutions. The general polarographic behaviour of the three substances is also described.
The effect of frequency of coaxial electrical stimulation on the peristaltic activity of the guinea-pig isolated ileum
Authors: VARAGIĆ V , KAẐIĆ T
Published: April 2011

Low frequency coaxial electrical stimulation (6/min to 5/sec) of the guinea-pig isolated ileum, arranged for recording peristalsis, was found either to stimulate or to maintain the existing peristaltic activity. High frequency stimulation (5/sec to 100/sec) was found to inhibit regularly the existing spontaneous peristaltic activity. The propulsive peristaltic action was also significantly diminished by high frequency stimulation. In a fatigued preparation all the applied frequencies produced the coordinated peristaltic contractions which were blocked by hexamethonium and by cooling. The propulsive activity of these contractions was higher after low frequency stimulation. It is suggested that block of peristalsis after high frequency stimulation might be due to activation of inhibitory elements in the gut.
A smooth muscle contracting substance in extracts of human umbilical cord
Authors: KARIM S M M
Published: April 2011

Aqueous extracts of human umbilical arteries and vein have been shown to contain a smooth muscle contracting substance. The active principle has been distinguished from smooth muscle contracting substances which are found in mammalian tissues, namely esters of choline, histamine, 5-hydroxytryptamine, bradykinin, angiotensin, and darmstoff. Evidence indicates that the smooth muscle stimulating activity of umbilical blood vessel extracts is due to a lipid-soluble unsaturated hydroxy acid. The possible physiological function of the active substance is discussed.
A note on the diffusion of drugs through artificial phospholipid membranes
Authors: MISRA ANAND L , HUNGER ALFRED , KEBERLE HEINRICH
Published: April 2011

A relatively simple method for the assessment of the passive diffusion of drugs through artificial phospholipid membranes composed of lecithin and collodion yields data on the permeability of some pharmaceutical substances through lipid barriers. Although there are inherent limitations in using artificial phospholipid membranes as substitutes for more complex biological membranes, this model system can furnish information on permeability kinetics and on the effect of structural groups on biological activity.
A note on perfusion with labelled compounds to determine intestinal absorption
Authors: KNOLL K R , PARKE R P , SWARTZ H A
Published: April 2011

An in vivo perfusion technique has been adapted for the measurement of intestinal absorption of labelled compounds. Salicylic acid, labelled with 14C, in solution with or without phenylephrine or caffeine, was perfused through the ligated and cannulated small intestine in situ of the rat. Absorption was estimated from the difference in count of the solutions entering the gut and the outflow which was sampled at 10 min intervals. Some 40–45% of the acid was found to be absorbed at each of three consecutive 10 min samplings. This was lower than, but consistent with, reported results derived by chemical assay. In the presence of the other two drugs the absorption of salicylic acid increased to 70%.
The effect of aprotic solvents on the adsorption of phenol by alumina
Authors: HIGGINS B , RICHARDS J H
Published: April 2011

The isotherms for the adsorption of phenol onto alumina from cyclohexane, benzene, nitrobenzene, ethyl acetate and 1,4-dioxan solutions have been determined at 25°. The change in solvent in the above order causes a successive decrease in the amount of phenol adsorbed at the ‘saturation level’ and possible explanations of the solvent effects are discussed.
The possible role of conformational isomerism in the biological actions of acetylcholine: spectral studies
Authors: MARTIN-SMITH M , SMAIL G A , STENLAKE J B
Published: April 2011

Infrared studies of the NC-H stretching frequencies of selected trimethylammonium salts, including acetylcholine, were made in an attempt to obtain evidence that intramolecular NC-H—O hydrogen bonding is responsible for the existence in solution of a quasi-ring conformation for acetylcholine. Acetylcholine and related compounds were also examined by nuclear magnetic resonance spectroscopy. The carbonyl stretching frequencies of an homologous series of acetoxy alkyl sulphones were measured in dioxan solution to gain information on the effect of electron withdrawing substituents in the absence of intermolecular hydrogen bonding. The observed high ester carbonyl absorption frequency in acetylcholine may be interpreted in terms of the inductive effect from the onium nitrogen atom but the results are not incompatible with the existence of a quasi-ring conformation involving C-H—O hydrogen bonding between one of the N-methyl groups and the acetoxy oxygen atom.
The use of the rabbit ear artery in the bioassay of catecholamines in urine
Authors: DE LA LANDE I S , GLOVER W E , HEAD R
Published: April 2011

Urine causes transient constriction of the isolated central artery of the rabbit ear. The substance responsible is qualitatively indistinguishable from noradrenaline when assessed by α-adrenergic blockade, sensitivity to oxidation by ferricyanide, behaviour on alumina, and comparison of dose response curves. The artery is equally sensitive to noradrenaline and adrenaline and approximately one hundred times less sensitive to dopamine. The results of bioassay, and chemical assay using the trihydroxyindole method, indicate that the constrictor response of the artery provides a useful guide to the urinary content of noradrenaline plus adrenaline.
The effect of α-methyldopa on excretion of noradrenaline metabolites
Authors: STOTT A W , ROBINSON R
Published: April 2011

The effect of α-methyldopa on the rate of release of noradrenaline metabolites in patients with essential hypertension has been examined. The excretion of normetadrenaline increases during the first few hr after a dose of α-methyldopa while α-methylnormetadrenaline can be detected in the urine 8–12 hr after the initial dose. The results support the idea that α-methyldopa displaces noradrenaline from storage sites, the noradrenaline in turn being replaced by α-methylnoradrenaline.
On the disposition of [3H]metaraminol in the rat salivary gland*
Authors: ALMGREN O , WALDECK B
Published: April 2011

The left salivary glands of rats were sympathetically denervated or decentralized. In some experiments the excretory ducts of the left submaxillary and sublingual glands were ligated to produce atrophy of the acinar cells. The rats received [3H]metaraminol (3H-MA) intravenously and were killed at various time intervals thereafter. The amount of 3H-MA in the salivary glands was determined. 3H-MA was taken up and retained in the intact gland, but disappeared rapidly from the denervated one, indicating that 3H-MA is taken up and stored in the adrenergic neuron. Decentralization resulted in a decreased turnover of the amine, especially during the first 18 hr, which supports the view that metaraminol is released by nerve activity. The ability of the salivary gland to take up 3H-MA was diminished by glandular atrophy, and the disappearance of the 3H-MA so taken up was delayed.
Carrageenans and the proteolytic activity of human gastric secretion
Authors: ANDERSON W , BAILLIE A J
Published: April 2011

The inhibition of the peptic activity of human gastric secretion by undegraded and degraded carrageenans of similar sulphate content has been examined over the pH range 1.5–3.75. Inhibition by degraded carrageenan is constant throughout this range, but inhibition by undegraded carrageenan decreases between pH 2.5 and 3.25, when a lower level is established. The inhibition by both types of carrageenan is caused by substrate-inhibitor interaction. The differences in degree of inhibition and the effect of pH on the inhibition by undegraded carrageenan appear to originate in the differing natures of the substrate-inhibitor complexes formed by degraded and undegraded carrageenans.
The morphology and anatomy of the flowers of Mitragyna ciliata Aubr. et Pellegr. and Mitragyna stipulosa (D.C.) O. Kuntze
Authors: SHELLARD E J , WADE A
Published: April 2011

The morphology and detailed anatomy of the flowers of Mitragyna ciliata Aubr. et Pellegr. and Mitragyna stipulosa (D.C.) O. Kuntze have been described. Although the histological features are almost identical, the two species can be differentiated by the morphology of their calices.
Production of cardio-active substances by plant tissue cultures and their screening for cardiovascular activity
Authors: KAUL BALKRISHENA , WELLS PATRICK , STABA E JOHN
Published: April 2011

Semi-purified extracts of six plant tissue cultures were examined for their effects on respiration, heart rate, and blood pressure in anaesthetized rabbits. Ammi visnaga, Cheiranthus cheiri, Digitalis lanata, and Urginea maritima evoked pronounced vasodilatation and bradycardia which ultimately resulted in the death of the animal.
A note on a series of decamethylenebis[(4-substituted amino)quinaldinium] salts with potent antibacterial properties
Authors: COX W A , LUNTS L H C
Published: April 2011

A number of decamethylenebis[4-(substituted amino)quinaldinium acetates] have been prepared and certain of these showed markedly increased antibacterial activity compared with the unsubstituted compound. Local therapeutic activity, assessed by mouse protection tests, reached a maximum in the C3–C6 range of the n-alkylamino-homologues, but increased activity was associated with increased toxicity.
Effects on the reproductive organs of feeding the non-ionic surfactant Triton X-100 to mice
Authors: GOLDHAMMER HELEN , McMANUS W R , OSBORN R A
Published: April 2011

A series of feeding experiments has shown Triton X-100 to induce cystic degeneration in the mouse ovary. Parallel experiments in ovariectomized mice revealed no evidence that Triton X-100 possesses oestrogenic activity. Long term exposure of female mice to this surfactant did not impair fertility.
The mechanism of the tranquillizing action of asarone from Acorus calamus Linn.
Authors: MENON M K , DANDIYA P C
Published: April 2011

Asarone, the active principle of the indigenous Indian plant Acorus calamus Linn., did not cause any change in the noradrenaline content of whole brain of rats. Unlike tetrabenazine, pretreatment with asarone failed to block the effect of reserpine on the spontaneous motor activity and ptosis of mice, as well as the conditioned avoidance response of trained rats. These findings show that, though in chemical structure asarone resembles a part of the reserpine molecule, its mechanism of action is different from this drug. In animals in which brain noradrenaline has been lowered by pretreatment with α-methyl-l-tyrosine, the effects of asarone, namely, hypothermia, potentiation of barbiturate hypnosis and specific blockade of conditioned avoidance response, were found to be markedly enhanced. It seems that the sedative effect of asarone is dependent on the depression of the ergotropic division of the hypothalamus.
A polarographic limit test for sulphoxide in chlorpromazine
Authors: PORTER G S
Published: April 2011

Twin cell subtractive cathode ray polarography can be used as a quantitative limit test for from 0.5% to 2.0% of chlorpromazine sulphoxide in chlorpromazine. 0.05% of the impurity is detectable by derivative polarography.
Dual actions of some N-(1-phenylethyl)guanidines on the nictitating membrane of conscious cats
Authors: FIELDEN R
Published: April 2011

After 6 hr, high doses (10 or 20 mg/kg) of some adrenergic neuron blocking drugs derived from N-(1-phenylethyl)guanidine produce relaxation of the nictitating membranes of conscious cats which is less than that produced by small doses (2.5 or 5 mg/kg). After 24 hr, there were marked responses to some drugs that had produced little effect after 6 hr. High doses of the drugs contract the nictitating membranes of cats treated with pempidine or (—)-N-(1-phenylethyl)guanidine; low doses do not. This contraction opposes the relaxation evoked by the adrenergic neuron blockade and could account for the anomalous dose-response relationships. The contraction may result from localized release of noradrenaline from the nictitating membrane.
Rhodexin A and rhodexoside in Ornithogalum umbellatum
Authors: SMITH J A , PATERSON G R
Published: April 2011

Two Kedde-positive compounds, isolated in crystalline form from bulbs of Ornithogalum umbellatum, were shown by their infrared and ultraviolet spectra to be cardenolides. Paper chromatographic analyses of the hydrolysates of these compounds indicated that both compounds contain sarmentogenin as the aglycone moiety, and that one is a rhamnoside while the other is the corresponding rhamnoside-glucoside. The identification of the monoglycoside as rhodexin A, i.e. sarmentogenin-α-L-rhamnoside, a glycoside previously isolated from Rhodea (Rohdea) japonica, was confirmed by comparison with an authentic sample. The diglycoside, an apparently new compound of composition sarmentogenin-rhamnose-glucose is designated rhodexoside.
Observations on isoprenaline-induced myocardial necroses
Authors: LESZKOVSZKY G P , GÁL GY
Published: April 2011

Isoprenaline hydrochloride in subcutaneous doses of 2 × 10 to 2 × 680 mg/kg caused histologically detectable, characteristic heart necroses. Pathological changes were dose-dependent. The degree of necrosis was assessed by a quantitative histological method based on counting the changed morphological elements. The heart necroses due to 2 × 40 mg/kg of isoprenaline were significantly inhibited by pretreatment with different monoamine oxidase inhibitors (iproniazid, a derivative of hydrazine and pargyline and E-250 of the non-hydrazine type, all at 7 × 50 mg/kg intraperitoneally); their severity was significantly increased by reserpine (7.5 mg/kg/48 hr subcutaneously) and guanethidine (2 × 30 mg/kg subcutaneously). In these effects an important role is attributed to respective changes in catecholamine levels.
Diffusion from gelatin-glycerin-water gels
Authors: NIXON J R , GEORGAKOPOULOS P P , CARLESS J E
Published: April 2011

The effect of gelatin, glycerin and methylene blue concentration on the diffusion of a dye from gelatin-glycerin-water gels has been examined. The rate of diffusion depended on the pore size of the gel and on the viscosity of the interspace fluid. Except at very low concentrations of methylene blue, an aggregation factor must be added to those factors suggested by Friedman & Kraemer (1930) as controlling the rate of diffusion from gels.
Quantitative determination of physostigmine in solution
Authors: TEARE F W , TAYLOR D W
Published: April 2011

A chemical assay is described for the indirect determination of physostigmine (eserine) in solution. The method involves a chemical reaction between methylamine, a hydrolysis product of physostigmine, and carbon disulphide to form a dithiocarbamic acid which is subsequently titrated with a standard aqueous sodium hydroxide solution. The alkaline hydrolysis of the physostigmine sample is carried out at room temperature using a closed system. The difference in the amount of methylamine found in a physostigmine hydrochloride solution before hydrolysis (blank) and after hydrolysis (sample) is indicative of the amount of intact alkaloid present. This indirect determination of methylamine makes it possible for the first time, to determine conveniently the amount of the alkaloid in solution in the presence of its degradation products.
Infrared identification of pharmaceutically important sulphonamides with particular reference to the occurrence of polymorphism
Authors: MESLEY R J , HOUGHTON E E
Published: April 2011

The infrared absorption spectra of sulphonamides, when compared with the spectra of Authentic Specimens, provide a simple and complete means of identification, provided the effects of polymorphism are excluded. Of 18 substances examined, twelve showed evidence of polymorphism. Limited solubility prevents the use of solution spectra, and specified solvent treatments, details of which are given, may therefore be necessary with these substances to ensure reproducible spectra.
Histidine decarboxylase in the stomach of the rat
Authors: RADWAN ABDALLA G , WEST G B
Published: April 2011

Two enzymes capable of decarboxylating l-histidine in vitro have been identified in rat and mouse stomach; one, located in the fundic portion, shows maximal activity at a pH value of 5.6, whilst the other, in the pyloric portion, requires a pH of 7.6 for optimal activity. The enzyme in rat fundus is stable when stored at low temperatures and is inhibited only slightly by benzene, α-methyldopa and α-methyl-histidine; the pyloric enzyme, on the other hand, is rapidly destroyed on storage at low temperatures, and is slightly stimulated by benzene but much inhibited by α-methyldopa and α-methylhistidine. Dopa and 5-hydroxytryptophan compete with the substrate for the pyloric histidine decarboxylase but have no effect on the fundic enzyme. Starvation inhibits the activity of the fundic enzyme but has only a slight effect on the pyloric enzyme. It is concluded that the two enzymes in the stomach capable of forming histamine differ from the specific and non-specific histidine decarboxylases found in other tissues.
Influence of nicotine on the coronary circulation of the isolated heart of the cat
Authors: ROMERO T , TALESNIK J
Published: April 2011

Nicotine administered to the isolated perfused heart of the cat produces initial bradycardia followed by long-lasting tachycardia and enhancement of the strength of contractions. The coronary flow after a reduction shows a prolonged increase that continues after the heart hyperactivity has ceased. When nicotine was given after hexamethonium or after reserpine pretreatment, the cardio-stimulation disappeared and only reduction of the coronary flow was obtained. It is concluded that the complexity of the pharmacological effect of nicotine on the coronary flow of the isolated heart preparation depends on an indirect vasodilator action mediated by the heart stimulation due to liberation of intracardiac catecholamines and also on vasoconstriction due to a direct effect of the drug on the coronary vasculature.
Influence of ω-amino-acids on blood pressure, catecholamine stores and the pressor response to physostigmine in the rat
Authors: Hedwall P R , Maiître L , Brunner H
Published: April 2011

The effects of aliphatic ω-amino-acids of various chain lengths, i.e. glycine, Γ-aminobutyric acid, s̀-amino-valeric acid, δ-aminocaproic acid and 7-amino-oenanthic acid, on blood pressure and myocardial catecholamine stores in the renal hypertensive rat, and the pressor response to physostigmine in the normotensive rat were studied. The effects of the ω-amino-acids were compared with those of guanethidine and α-methyldopa. δ-Aminocaproic acid, like guanethidine and α-methyldopa, produced a fall in blood pressure, a decrease in catecholamine stores and inhibited the pressor response to physostigmine. GABA reduced blood pressure, but did not affect the other parameters. s̀-Amino-valeric acid reduced blood pressure and depleted catecholamine stores slightly, but did not inhibit the pressor response to physostigmine. The other ω-amino-acids were inactive.
The biotransformation of methadone in man: Synthesis and identification of a major metabolite
Authors: Beckett A H , Taylor J F , Casy A F , Hassan M M A
Published: April 2011

After administration of methadone to man, only two basic urinary excretion products were detected, these were unchanged drug and 2-ethyl-1, 5-dimethyl-3, 3-diphenyl-1-pyrroline. The hydriodide of the latter was synthesized and its endocyclic alkene structure was confirmed from infrared and nuclear magnetic resonance spectral data. This compound was shown to be identical with the hydriodide of the basic product formed by reaction of 1, 5-dimethyl-3, 3-diphenylpyrrolid-2-one with ethyl-lithium.
A note on the effects of 2, 4-diamino-5-phenylthiazole and 1, 2, 3, 4-tetrahydro-9-aminoacridine on morphine metabolism
Authors: Woo J T C , Gaff G A , Fennessy M R
Published: April 2011

Chromatographs of extracts of urine from patients receiving mixtures of morphine plus amiphenazole or morphine plus 1, 2, 3, 4-tetrahydro-9-aminoacridine (tha) have a spot which is due to a substance with properties similar to morphine-N-oxide. This spot was not present in urine of patients given morphine, amiphenazole or tha alone. Morphine-N-oxide may be a metabolite of morphine, and amiphenazole and tha may inhibit the further metabolism of morphine-N-oxide.
1-Allyl and 1-(3, 3-dimethylallyl) analogues of pethidine and its reversed ester
Authors: Casy A F , Simmonds A B , Staniforth D
Published: April 2011

The preparation of some 1-allyl and 1-(3, 3-dimethylallyl)-4-phenylpiperidines related to pethidine and its reversed ester is described and the hot-plate activities in mice of these compounds reported. All six derivatives displayed morphine-like properties in mice, four being more potent (1·5–6 times) than morphine, but failed to act as analgesic antagonists in rats. The results are contrasted with the properties of similarly N-substituted fused-ring analgesics and differences discussed in terms of drug-receptor interaction modes.
Solubilization of griseofulvin by nonionic surfactants
Authors: Elworthy P H , Lipscomb F J
Published: April 2011

Four nonionic surfactants, Me[CH2]15·[OCH2·CH2]xOH where x = 10, 22, 45 and 60, and polyoxyethylene glycols 200, 400 and 1000 increased the solubility of griseofulvin over its value in water. Cetomacrogol micelles solubilize two molecules of griseofulvin per micelle. The site of solubilization seems likely to be the polyoxyethylene part of the micelles. The partial molal heats and entropies of solution decrease as surfactant or polyoxyethylene glycol concentration is increased.
A note on the stability of emulsions at high dilution
Authors: Shotton E , Davis S S
Published: April 2011

The behaviour of liquid paraffin-potassium laurate emulsions has been investigated at high dilution using the Coulter Counter, microelectrophoresis, and centrifugation. The results show that the state of the oil-water interface is dependent on emulsifier concentration below and above the critical micelle concentration.
Simulation methods in drug screening
Authors: Davies O L
Published: April 2011

Simulation is used to give a quantitative explanation of the phenomenon frequently observed in routine drug screening, that activities found in the initial tests are not confirmed on retest. Simulation is also used to assess the efficiency of a screening test procedure and to compare the efficiencies of different procedures.
The guinea-pig isolated vas deferens: A method for increasing sensitivity to drugs
Authors: Thoa N B , Maengwyn-Davies G D
Published: April 2011

A preparation of the guinea-pig vas deferens was developed in which it was opened along its length. It was sufficiently sensitive to obtain reproducible dose-response curves to acetylcholine, noradrenaline, histamine, nicotine, 5-hydroxytryptamine and potassium chloride; it was more sensitive than the unopened vas deferens.
The role of calcium in neurohumoral and neurohormonal extrusion processes
Authors: Simpson Lance L
Published: April 2011

CALCIUM is a divalent cation, ubiquitous in its biological occurrence, important in its physiological significance. It is an ion of particular interest to investigators of neural and neuro-effector systems. Reviews have appeared that cite the role of calcium in excitation-contraction coupling of striate muscle (Sandow, 1965) and in the maintenance of the nerve membrane during nervous transmission (Abood, 1967). The intention of this review will be to summarize the various experimental evidences that implicate calcium in its role as a necessary factor in the processes of neurohumoral and neurohormonal extrusion. The diversity of physiological foci considered has meant that the discussion could not feasibly cite all primary references. Consequently, an attempt has been made, when applicable, to note recent and well prepared reviews.
Lack of inter-action between propranolol and mebanazine
Authors: Barrett A M , Cullum Valerie A
Published: April 2011

It has been suggested that treatment with monoamine oxidase inhibitors should be withdrawn 2 weeks before commencing treatment with an adrenergic β-receptor blocking drug e.g. propranolol. Experiments in anaesthetized cats have failed to unmask any undesirable property of propranolol following amine oxidase inhibition. Furthermore, combined treatment with both types of drug reduced the cardiovascular responses to intravenous tyramine and amphetamine. The pressure response to intraduodenal tyramine was no greater in animals treated with both drug types compared with that in cats receiving amine oxidase inhibitor alone, whereas the tachycardia was much reduced.
The effect of some non-ionic surfactants and a polyoxyethylene glycol on the dissolution rate of griseofulvin
Authors: Elworthy P H , Lipscomb F J
Published: April 2011

Measurements of the dissolution rate of griseofulvin in water, four non-ionic surfactants, and a polyoxyethylene glycol have been made. These results are analysed in terms of a zero order rate constant (k1) for transfer of the drug from the crystal to the bulk of the solution, and a first order constant (k2) for the reverse process. Surfactants greatly increase the dissolution rate, increasing k1 and decreasing k2. Polyoxyethylene glycol is not so effective as the surfactants at increasing dissolution rates. In an attempt to interpret k1 and k2, it appears that both chemical and transport processes are involved in the dissolution, the presence of surfactant decreasing the energy change for transferring griseofulvin molecules from the crystal to the solution.
Potentiation by cocaine and 3,3-di(p-aminophenyl)-propylamine (TK 174) of the effect of isoprenaline and noradrenaline on isolated strips of cat spleen
Authors: Leszkovszky G P , Tardos L
Published: April 2011

Contractions of cat isolated spleen strips by noradrenaline and isoprenaline are brought about by interaction with α-adrenergic receptors. The effect of isoprenaline cannot be diminished by in vivo reserpine pretreatment. The effects of both noradrenaline and isoprenaline are potentiated by cocaine and by a new diphenyl-propylamine derivative TK 174 [3,3-di(p-aminophenyl)propylamine]. Noradrenaline is potentiated more by TK 174 than by cocaine while the reverse is seen with isoprenaline. These results suggest that beside the inhibition of noradrenaline uptake another factor may be involved in the mechanism of action of cocaine, and to a lesser extent of TK 174.
A note on the blockade of uptake of noradrenaline by 4-chloro-αα-dimethylphenethylaminopropan-2-one in rodents
Authors: Lippmann W
Published: April 2011

4-Chloro-αα-dimethylphenethylaminopropan-2-one blocked uptake of [3H]noradrenaline in the heart, had no effect on the endogenous levels of catecholamines or 5-hydroxytryptamine in the heart, brain or adrenals and decreased the [3H]noradrenaline-depleting activity of metaraminol, but not reserpine, in rodents. The compound appears to act by interfering with the active transport of noradrenaline through the nerve cell membrane.
Central hypotensive effect of α-methyldopa
Authors: Henning M , Van Zwieten P A
Published: April 2011

In cats under chloralose anaesthesia l-α-methyldopa (20 mg/kg) was infused for 1 hr into the left vertebral artery. One to 3 hr after the end of the infusion a gradual and significant lowering of mean arterial blood pressure was observed. The dopamine and noradrenaline contents of the brain were significantly reduced while brain 5-hydroxytryptamine and heart noradrenaline concentrations remained normal. The same low dose of l-α-methyldopa infused into a systemic vein did not affect the blood pressure. However, brain dopamine and noradrenaline were depleted to the same extent as observed after infusion into the vertebral artery. Intravenous infusion of a large dose of l-α-methyldopa (200 mg/kg) did not significantly alter mean arterial blood pressure but lowered brain dopamine, noradrenaline and 5-hydroxytryptamine levels. No effect on heart noradrenaline was observed. Infusion of saline or the d-isomer of α-methyldopa (20 mg/kg) into the vertebral artery had no effect on blood pressure or tissue monoamines.
Protection by ethanol against the toxic effects of monofluoroethanol and monochloroethanol
Authors: Peterson D I , Peterson J E , Hardinge M G
Published: April 2011

Ethanol protects rats and monkeys against fatal doses of monofluoroethanol and monochloroethanol. In rats treated with ethanol the LD50 for fluoroethanol was found to be more than 20 times that in unprotected animals, for chloroethanol it was about 4 times greater. In monkeys too, the lethal effects of these compounds are diminished by treatment with ethanol.
Anethole and fenchone in the developing fruits of Foeniculum vulgare Mill
Authors: Betts T J
Published: April 2011

The anethole and fenchone content of the developing fruits of bitter and sweet varieties of Foeniculum vulgare Mill, (fennel) has been assayed by gas chromatography over three seasons. Anethole continuously increases in both varieties to about 22 mg/100 fruits. Fenchone is present at all stages of development of both varieties, and continuously increases to about 10 mg and 2 mg/100 fruits in the bitter and sweet varieties respectively. Greater oil yields from the bitter fruit are thus due to their higher fenchone content and lower weight.
Recovery of noradrenaline in adrenergic axons of rat sciatic nerves after reserpine treatment
Authors: Dahlström Annica , Häggendal Jan
Published: April 2011

The recovery of noradrenaline in adrenergic axons of the rat sciatic nerve after a single dose of reserpine (10 mg/kg i.p.) has been studied in unligated nerves and nerves ligated for 6 h. In unligated nerves the recovery at 24 h after reserpine was about 14% of normal. The noradrenaline content then slowly rose to reach about normal concentrations 6–7 days after reserpine injection. In nerves ligated 6 h before death, about 8·0 ng of noradrenaline accumulated proximal to the ligation in normal animals. At 6 and 12 h after reserpine about 4% of normal amounts of noradrenaline were found. Thereafter the amount of accumulated noradrenaline rapidly increased to about normal levels on day 2 after reserpine. At this time the content in unligated nerves was only about 45% of normal unligated nerve. On days 3–5 after reserpine, supranormal accumulations of noradrenaline were found (statistically highly significant), having a maximum at day 4 of about 145% of normal. At this time the noradrenaline content in unligated nerve was only about 80% of normal. The results may indicate an increased synthesis and increased rate of downtransport of amine storage granules during the early recovery phase after reserpine. This phenomenon may be part of a feed-back mechanism operating after depletion of the transmitter in the nerve terminals.
Some effects of dihydroergocristine and of phentolamine mesylate on renal function in rats
Authors: Lockett Mary F , Stuart D L , Wadley Rosalie , Goss A R , Siddiqui H H
Published: April 2011

Single injections of dihydroergocristine (dhe) (25, 50 and 100 μg, i.p.) did not depress the systemic arterial pressure but antagonized the pressor effects of (-)-noradrenaline (100 μg, s.c.) in unanaesthetized rats. The effects of these doses of dhe on water diuresis were minimal: slight K retention, a rise in urinary Na:K and a slight but significant fall in the clearance of p-aminohippuric acid were noted. Single injections of phentolamine mesylate (10, 20 and 40 μg, i.p.) greatly depressed systemic arterial pressure and reduced the glomerular filtration rate and p-aminohippuric acid clearance and the excretion of water and Na proportionately, but markedly. The Na:K in the urine rose. Chemical denervation of the kidneys either with dhe, 32 μg, or phentolamine, 2 mg, thrice daily for 5–7 days decreased, but for 14 days increased, the juxtaglomerular index of the kidneys. Parallel changes were found in the extractable renin. Continued treatment with dhe (32 μg thrice daily for 2 weeks) raised, and hyperduric adrenaline (250 μg twice daily for 1 week) lowered the stores of growth hormone in the adenohypophysis. Continued treatment with dhe, 32 μg thrice daily produced antidiuresis and retention by the third day lasting to the fifth. This condition had reversed by the eighth day.
The effect of SC-15396, atropine and mepyramine on gastrin-, bethanechol- and histamine-stimulated gastric acid secretion in rats and guinea-pigs
Authors: Albinus Margitta , Sewing K-Fr
Published: April 2011

The effect of SC-15396 (“antigastrin”; 2-phenyl-2-(2-pyridyl)thioacetamide), atropine and mepyramine on gastrin-, bethanechol- and histamine-stimulated gastric acid secretion was studied in rats and guinea-pigs. For all three stimulants parallel dose response curves were obtained except in guinea-pigs where bethanechol even in very high doses displays a poor activity in stimulating gastric acid secretion. The maximal secretory response was found to be 12·7 ± 5·0 μ-equiv HCl/10 min in rats and 53·2 ± 27£9 μ-equiv HCl/10 min in guinea-pigs. All stimulating effects on gastric acid secretion were reduced by SC-15396; atropine abolished the secretory responses to bethanechol. Mepyramine was ineffective. In accordance with these findings the mechanism of action of gastrin and a receptor model on the oxyntic cell are discussed.
The actions of atropine, tropenziline and N-butyl hyoscine bromide on the isolated distal colon of the guinea-pig: a comparison of their activities and mechanisms of action
Authors: Lecchini S , Del Tacca M , Soldani G , Frigo G M , Crema A
Published: April 2011

In the guinea-pig isolated distal colon, the order of anticholinergic activity is as follows: atropine > tropenziline bromide > N-butyl hyoscine bromide. The reduction in the responses to pelvic and transmural stimulation produced by tropenziline and N-butyl hyoscine bromide is due partly to their ganglion blocking activity. This effect also explains the reduction they cause in acetylcholine output on pelvic nerve and transmural stimulation. Since atropine also reduces acetylcholine release on pelvic nerve stimulation, it is suggested that muscarinic receptors of the parasympathetic ganglia are involved in transmission of pelvic nerve impulses.
Gas chromatographic identification of thioridazine in plasma, and a method for routine assay of the drug
Authors: Curry S H , Mould G P
Published: April 2011

Thioridazine had a retention time of approximately 4 min on a 3% OV-17 gas chromatographic column at 260°. Using flame or argon ionization detectors samples as low as 0μ01 μg could be detected. The drug could be extracted into n-heptane containing 1·5% isoamyl alcohol or 20% toluene. Recovery of drug added to plasma was 100%. Unchanged thioridazine was identified in the plasma of two experimental samples, on the basis of chromatographic and solvent distribution data.
Identification of a urinary metabolite of perazine as a piperazine-2,5-dione derivative
Authors: Krauss Dietlinde , Otting Walter , Breyer Ursula
Published: April 2011

A non-basic perazine metabolite has been isolated from the urine of schizophrenic patients ingesting perazine. Identification of this compound as 10-[3‘-(2“,5”-dioxo-4“-methyl-piperazinyl)-propyl]-phenothiazine sulphoxide was achieved using ultraviolet, infrared, nuclear magnetic resonance and mass spectroscopy.
The effects of etorphine and of morphine on respiration, blood carbon dioxide tension, and carbon dioxide sensitivity in the conscious rabbit
Authors: Pleuvry Barbara J , Rees J M H
Published: April 2011

The effects of intravenous doses of morphine and etorphine on respiration, blood pCO2 and sensitivity to carbon dioxide were investigated in the conscious rabbit. Both morphine and etorphine depressed respiratory rate and elevated pCO2. Etorphine was about 5000 times more potent than morphine as a depressant of respiratory rate. With etorphine, depression of respiratory rate was always accompanied by a large increase in tidal volume. In the normal rabbit, inhalation of mixtures of carbon dioxide up to 15% (in oxygen) produced a concentration-dependent increase in tidal volume accompanied by no increase in respiratory rate. After injection of morphine followed by inhalation of carbon dioxide there was a dose-dependent depression of carbon dioxide sensitivity which was concurrent with the depression of respiratory rate; 8 mg/kg completely abolished the respiratory stimulant effects of concentrations of carbon dioxide up to 12%. Whilst high doses of etorphine depressed carbon dioxide sensitivity, a dose of 0·5 μg/kg (which depressed respiratory rate by about 30%) did not depress carbon dioxide sensitivity. Doses of 1 μg/kg of etorphine administered to pregnant animals produced an increase in respiratory rate and a depression of tidal volume. The significance of the differences between the respiratory pharmacology of etorphine and that of morphine is discussed.
The determination of cellulase activity by viscometry
Authors: Joos P , Sierens W , Ruyssen R
Published: April 2011

The enzymatic activity of cellulase has been estimated by the decrease of viscosity of a hydroxyethylcellulose solution as a function of incubation time. This decrease is a function of the applied shear stress. It is proposed that the viscosity be measured in an ordinary Ostwald viscometer under conditions where the viscosity is Newtonian, that is, the decrease of viscosity by enzymatic activity is independent on the shear stress.
Dissolution rates of sparingly soluble tablets
Authors: Hersey J A , Barzilay R B
Published: April 2011

The automated dialysis method offers an opportunity for the accurate evaluation of the dissolution rates of sparingly soluble dosage forms. By the analysis of kinetic models, the dissolution rates for disintegrating and non-disintegrating dosage forms may be calculated. The theory is used to examine the effect of additives and compression force on the dissolution rates of sulphathiazole tablets. At the fairly low compression forces used (640–1430 kg) the dissolution rate gradually increases due to penetration of the tablet by the dissolution medium. Polyethylene oxide causes an initial rapid increase in dissolution rate, but the formation of a mucilaginous film results in a constant rate. Using starch, dissolution rate increases rapidly as a result of tablet disintegration. This disintegration is shown to make available less than half the surface area of the original powder. The dissolution rate constant for sulphathiazole under the experimental conditions is 2–75 × 10−4 cm min−1.
Stabilization of oil-in-water emulsions by non-ionic detergents: properties of synthetic detergents at anisole- and chlorobenzene-water surfaces
Authors: Elworthy P H , Florence A T
Published: April 2011

As part of an investigation into the mechanisms of stabilization of emulsions, the interfacial activity of three synthetic non-ionic detergents, CH2·[CH2]15·[O·CH2·CH2·]xOH, with x = 3, 6 and 9, at the anisole-water and chlorobenzene-water interface has been determined by measurement of interfacial tension. Surface pressure (π)-area (A) relations have been derived. The films are more expanded than at the air-water interface and an equation of the form (π- πR)A = xkT fits the results. It is suggested tentatively that πR, which is in most cases positive, and which increases with polyoxyethylene chain length, arises from the interaction between the ethylene oxide chains as they approach closely. The apparent critical micelle concentrations determined from the interfacial tension-concentration curves are higher than the true critical micelle concentrations obtained at the air-water interface.
Adrenergic receptors in the guinea-pig trachea
Authors: Everitt B J , Cairncross K D
Published: April 2011

The effects of adrenaline, noradrenaline and isoprenaline have been investigated on the guinea-pig isolated trachea in the presence of propranolol hydrochloride 10−5 and 10−6 g/ml. Adrenaline and noradrenaline were both shown to produce contractions of the tissue. The relative order of potency of the catecholamines (adrenaline > noradrenaline > isoprenaline), together with the antagonism exhibited by phenoxybenzamine, suggests that the contractions were due to α-adrenergic receptor involvement.
Relative activity of prostaglandins E1, A1, E2 and A2 on lipolysis, platelet aggregation, smooth muscle and the cardiovascular system
Authors: Weeks J R , Chandra Sekhar N , Ducharme D W
Published: April 2011

The relative activities of four prostaglandins (PGE1, PGA1, PGE2 and PGA2) were determined in several biological tests. They were compared as intestinal muscle stimulants on rabbit duodenum and guinea-pig ileum, as inhibitors of adrenaline-induced lipolysis in rat isolated epididymal fat, inhibitors of platelet aggregation in rabbit plasma, as vasodepressor agents in anaesthetized rats and dogs, and on both blood pressure and cardiac output in unanaesthetized dogs. Formation of PGAs by dehydration and introduction of one additional double bond virtually abolished activity in all of these systems except the cardiovascular system. PGE2 was more active than PGE1 on isolated rabbit duodenum and as an antilipolytic agent, but less active in the other systems. Only PGE1 had high potency as an inhibitor of platelet aggregation.
Relation of brain sensitivity and hepatic metabolism of hexobarbitone to dose-response relations in infant and young rats
Authors: Kalser Sarah C , Forbes Eleanore , Kunig Rosemarie
Published: April 2011

The dose-response relation to hexobarbitone of infant (5 day) and young (44 day) male rats was examined, and the relative contribution of hepatic metabolism (measured in vitro) and changes in brain sensitivity to the overall response were evaluated. The infant rat shows a parallel shift to the left in its dose-response curve with the relative potency of hexobarbitone almost 5 times greater than for the 44 day old animal. The slope of the curves show marked changes at the first lethal dose level of drug. This and other evidence suggest that death may not be merely an extension of the mechanism causing hypnosis. Infant rats exhibited a shorter increment in sleep time for increasing doses of hexobarbitone than is predictable from their low rate of in vitro metabolism. Although this is also true for the young rats, the two values are in much closer agreement than for the infant animals. Brain concentrations of hexobarbitone, measured upon regaining of the righting reflex, were lower in the infant than in the young rat. This suggests the central nervous system of the infant rat has an increased sensitivity to the drug.
Kinetics of the hydrolysis of phosphatidylcholine and lysophosphatidylcholine
Authors: Marriott P H
Published: April 2011

An experimental technique capable of estimating as little as 10 nano-equivalents of long-chain carboxylic acids (fatty acids) has been used to study the decomposition of phospholipids. The rate of release of acids varied with the monovalent cation which was associated with the hydroxyl ion in the hydroxide used. Because the concentration of hydroxide was much greater than the concentration of phospholipid, the rate of hydrolysis was first order with respect to the phospholipid. The pseudo-first order reaction velocity constant varied as the first power of the concentration of lithium hydroxide, but as the second power of the concentration of potassium, sodium, tetramethylammonium, or tetraethylammonium, hydroxides. It is postulated that (i) lecithin and lysolecithin, in strong alkaline solution, bind lithium ions much more strongly than potassium, sodium, tetramethylammonium, or tetraethylammonium ions, and (ii) it is only this cation-phospholipid complex which is broken down by hydroxyl ions.
Esters of choline and β-trimethylammoniopropionic acid: geometrical isomerism and anti-acetylcholinesterase activity
Authors: Kay J B , Robinson J B
Published: April 2011

The preparation of the choline esters of cis- and trans-4-t-butylcyclohexanecarboxylic acid is reported. The similar inhibitory potency displayed by these isomers towards the acetylcholinesterase catalysed hydrolysis of acetylcholine is explained on the basis of the binding of a thermodynamically unstable conformation of the cis-isomer to the active site. Similar studies employing the β-trimethylammoniopropionate esters of cis- and trans-4-t-butylcyclohexanol suggest that the “reverse esters” do not bind to the active site in an identical manner to the acylcholines.
Anticholinergic effects and passage through the intestinal wall of N-butylhyoscine bromide
Authors: Pomeroy A R , Rand M J
Published: April 2011

The effects of N-butylhyoscine bromide (Buscopan) were examined on responses of guinea-pig isolated intestine to transmural stimulation and to peristalsis induced by raising the intraluminal pressure. The drug acted rapidly and in low concentration to abolish peristaltic activity and responses to transmural stimulation when applied to the serosal surface of the ileum, but from 100 to 1000 times the concentration was required when it was applied to the mucosal surface. The effects were more persistent after mucosal than after serosal application. N-Butylhyoscine bromide was bound to mucus and mucosal material, the ratio of free to bound drug being 2:1. The drug passed through portions of the intestinal wall containing Peyer’s patches more rapidly than through portions containing no macroscopically visible lymphoid tissue. The rate of passage through Peyer’s patches, but not through other portions, increased with increasing hydrostatic pressure. These findings help to explain why enterally administered N-butylhyoscine bromide exerts anti-cholinergic effects on the gut without producing systemic actions.