bluuebunny/crossref_metadata_2025 huggingface dataset:
METABOLISM AND EXCRETION OF DI(p‐AMINOPHENYL) SULPHOXIDE IN DIFFERENT ANIMAL SPECIES
Authors: LEVI A. A. , SNOW G. A.
Published: July 2012

Rabbits, rats and guinea‐pigs were treated with di(p‐aminophenyl) sulphoxide and their urines examined by an analytical method which permits the simultaneous determination of this compound and of sdapsone [di(p‐aminophenyl) sulphone] which is a possible product of metabolic oxidation. The method gives for each drug the total of free compound plus acid‐labile conjugates. All three species excreted unchanged drug together with dapsone. With rats and guinea‐pigs about 33% of the excretion is dapsone, but with rabbits only 6 to 12%. The rate of combined excretion is much greater in rabbits than in the other two species. These results are discussed in relation to the significance of di(p‐aminophenyl) sulphoxide as a drug in the treatment of leprosy.
THE EFFECTS OF ADRENALINE AND NORADRENALINE ON THE METABOLISM AND PERFORMANCE OF THE ISOLATED DOG HEART
Authors: FAWAZ G. , TUTUNJI B.
Published: July 2012

In 16 dog heart‐lung preparations modified to permit a more accurate measurement of coronary flow, adrenaline or noradrenaline was infused at a rate of 4 μg. base/min. After a 30‐min. pause during which the increased oxygen consumption and heart rate, but not the coronary flow, returned to pre‐infusion levels, the other sympathomimetic amine was infused for the same length of time. It was found that, mole per mole, noradrenaline is as effective, and probably more so, than adrenaline in raising the oxygen consumption of the heart‐lung preparation. The positive chronotropic and coronary dilating action of both amines appear to be equal. It was observed that in any one experiment the second dose of the sympathomimetic amine was slightly more effective than the first dose in raising the oxygen consumption. The level of high‐energy phosphorus compounds does not change after adrenaline or noradrenaline administration even at the time when the oxygen consumption rises to as much as 200%. During this period there are no signs of cardiac hypoxia, as can be judged by the good oxygen saturation of coronary venous blood. Single doses of 5 μg. adrenaline or noradrenaline have a consistent positive inotropic effect that lasts about 15 min. when tested on a failing heart. In 12 experiments on non‐failing modified heart‐lung preparations, a single dose of 5 μg. adrenaline fails to cause a measurable increase in oxygen consumption after 1, 3, 6, or 11 min. in spite of a mild positive chronotropic action. The significance of these findings is discussed and the suggestion made that, when noradrenaline infusions are effective in treating cardiogenic shock in man, part of this effect may be due to its positive inotropic action, thus correcting an element of heart failure that might exist.
THE INHIBITION BY MORPHINE OF THE ACTION OF SMOOTH MUSCLE STIMULANTS ON THE GUINEA‐PIG INTESTINE
Authors: LEWIS G. P.
Published: July 2012

Morphine and related analgesics depress the responses of the isolated guinea‐pig ileum to nervous stimulation and to drugs which act by stimulating the nervous structures of the intestinal wall. The present experiments show that these analgesics also depress the responses to smooth muscle stimulants which act directly on the smooth muscle fibres.
THE EFFECT OF MORPHINE ON THE ADRENERGIC NERVES OF THE ISOLATED GUINEA‐PIG JEJUNUM
Authors: SZERB J. C.
Published: July 2012

Nerves accompanying the mesenteric blood‐vessels of the isolated guinea‐pig jejunum were stimulated and changes in the longitudinal muscle coat were recorded. Stimulation of the nerves led to a rapid relaxation if the intestine was contracted by a previous administration of histamine. The relaxation was inhibited by morphine and partially restored by nalorphine. Bretylium and atropine also inhibited the relaxation and cocaine increased it somewhat. Morphine, atropine, and bretylium had no significant effect on the depressant action of noradrenaline on histamine contractions, whereas cocaine slightly enhanced the action of noradrenaline. Morphine, but not the other drugs, prevented the inhibitory action of dopamine.
UPTAKE OF LABELLED NORADRENALINE BY ISOLATED ATRIA
Authors: BURN G. P. , BURN J. H.
Published: July 2012

The uptake of labelled noradrenaline by isolated rabbit atria has been studied, and the rate of outflow of radioactivity after a period of loading has been recorded. There is first a rapid outflow presumably from extracellular space, followed by a slow outflow presumably from intracellular space. Cocaine greatly diminished the intracellular uptake. Tyramine caused an increased outflow of radioactivity from intracellular sites which was not due to the increase in atrial rate, since noradrenaline which increased the rate more than tyramine had less effect on the outflow.
SOME EFFECTS OF CORTICOSTEROIDS ON THE METABOLISM OF HISTAMINE AND 5‐HYDROXYTRYPTAMINE IN THE RAT
Authors: TELFORD J. M. , WEST G. B.
Published: July 2012

Daily intramuscular injections of cortisone, prednisolone, triamcinolone, fludrocortisone and 2‐methylfludrocortisone reduced the histidine decarboxylase activity of the rat liver, but increased the enzyme activity of the pyloric stomach. Injections of histamine liberators or exposure to cold produced similar changes. After adrenalectomy, the histidine decarboxylase activities of the liver and pyloric stomach were unaltered, but the histaminase activity of the ileum was reduced. The 5‐hydroxytryptophan decarboxylase activities of rat liver and kidney were not altered by treatment with corticosteroids.
EFFECT OF MORPHINE ON SOME SYMPATHETICALLY INNERVATED EFFECTORS
Authors: CAIRNIE A. B. , KOSTERLITZ H. W. , TAYLOR D. W.
Published: July 2012

Morphine, in doses of 0.5 to 55 mg/kg, inhibited contraction of the nictitating membrane of the cat following stimulation of the postganglionic sympathetic nerve fibres. Morphine was more effective at low than at high frequencies of stimulation, independently of the size of contraction of the membrane; the speed of contraction was reduced at all frequencies. Cocaine potentiated the contraction of the nictitating membrane following nerve stimulation more at low than at high frequencies, and antagonized the action of morphine. These findings, and the absence of an effect of morphine on the action of injected noradrenaline, make it likely that morphine interferes with the release of noradrenaline from the postganglionic nerve endings in the nictitating membrane. Morphine had no effect on the cardioaccelerator action of the cardiac nerves and inconsistent results were obtained on the emptying of the spleen after stimulation of the splenic nerves.
INFLUENCE OF DICHLOROACETYLATION ON THE ANTIMICROBIAL ACTIVITY OF CHLORAMPHENICOL DERIVATIVES AND OF VARIOUS AMINES
Authors: LOGEMANN W. , ALMIRANTE L. , GALIMBERTI S. , DE CARNERI I.
Published: July 2012

The dichloroacetyl group, one of the functional groups responsible for the anti‐bacterial activity of chloramphenicol, has been inserted into various amines, and the dichloroacetamido‐derivatives obtained have been studied against E. histolytica EdM, Candida albicans ATCC 2091, Saccharomyces cerevisiae ATCC 7921, Aspergillus niger NRRL 3, Trichomonas vaginalis and Mycobacterium tuberculosis H37Rv and ATCC 607. Among the various chlorophenoxamide analogues, only N‐(benzothiazol‐2‐ylmethyl)dichloro‐N‐2‐hydroxyethylacetamide shows an activity, in vitro and in vivo, comparable with that of chlorophenoxamide. The dichloroacetyl group is essential for the high amoebicidal activity in vivo of chlorophenoxamide. The dichloro‐acetamidopropiophenones of known antifungal activity also show marked amoebicidal activity in vitro, but they appear to have a different mechanism of action from chloro‐phenoxamide since the dichloroacetyl group is not indispensable. The high anti‐tubercular activity of some benzothiazole derivatives is not increased by dichloro‐acetylation.
SOME COCAINE‐LIKE ACTIONS OF 3‐PHENOXYPROPYLGUANIDINE
Authors: BARTLET A. L.
Published: July 2012

In anaesthetized cats 3‐phenoxypropylguanidine caused a contracture of the nictitating membrane, a dilatation of the pupil and a fall followed by a rise in the arterial blood pressure. In spinal preparations of cats the initial fall in blood pressure was usually absent and the rise in blood pressure subsided to a steady level, which was about 10 mm Hg above the initial pressure. The pressor action and the contracture of the nictitating membrane were inhibited by phenoxybenzamine and by previous treatment with reserpine, but were not abolished by adrenalectomy and bretylium. 3‐Phenoxypropylguanidine potentiated the actions of adrenaline and noradrenaline, increased the blood glucose concentration of the rabbit and decreased the appetite of the cat. The action of tyramine on the cardiovascular system was inhibited by 3‐phenoxypropylguanidine, but the stimulant action of tyramine on the nictitating membrane of the cat was not abolished by this substance. Although 3‐phenoxypropylguanidine produced a local anaesthesia of long duration in guinea‐pig skin, it failed to anaesthetize the rabbit cornea. The responses to stimulation of the preganglionic cervical sympathetic nerve of the cat and the great auricular nerve of the rabbit ear were not abolished by 3‐phenoxypropylguanidine; neither did this substance abolish the nicotinic action of acetylcholine in atropinized cats. Contractions of the rat fundus to tryptamine and 5‐hydroxytryptamine were antagonized by 3‐phenoxypropylguanidine, but were potentiated by cocaine.
EFFECTS OF SOME ISOMERS AND ANALOGUES OF NICOTINE ON JUNCTIONAL TRANSMISSION
Authors: BARLOW R. B. , HAMILTON J. T.
Published: July 2012

A number of isomers and homologues of nicotine, (2‐, 3‐ and 4‐pyridylmethyl)‐and [2‐(2‐, 3‐ and 4‐pyridyl)ethyl]‐dialkylamines and trialkylammonium salts, have been prepared. They have been tested for their ability to act like acetylcholine in causing contracture of the chick biventer‐cervicis and, some of them, for their ability to stimulate the superior cervical ganglion of the cat, causing contracture of the nictitating membrane. All the compounds have been tested for their ability to block transmission on the superior cervical ganglion of the cat and on the rat diaphragm preparation, and most of them for ability to inhibit the enzymatic hydrolysis of acetylcholine, using an acetone‐powder of dog caudate nucleus as a source of acetylcholinesterase. The dissociation constants of the compounds have been measured by electrometric titration. The dissociation constants were used to compute the amount of monovalent ion present in the conditions of the biological tests, and the activities of the compounds have, accordingly, been compared on an ionic, as well as on a molecular, basis. The two sets of figures do not differ greatly. Trimethyl[2‐(3‐pyridyl)ethyl]ammonium (23) was the most potent compound on the chick and cat preparations. On an ionic basis (that is, compared with the monovalent nicotinium ion) this was 2.6 times as active as nicotine on the chick biventer and 11 times as active on the cat superior cervical ganglion. On the rat diaphragm it was 7.1 times as active as nicotine and less active than 1‐methyl‐1‐(3‐pyridylmethyl)‐pyrrolidinium (26) (9.5 times the nicotinium ion) and trimethyl(4‐pyridylmethyl)‐ammonium (21) (11 times). The relationships between structure and dissociation constant, anticholinesterase activity, and activity in the pharmacological tests have been discussed.
EFFECT OF β‐DIETHYLAMINOETHYL 3,3‐DIPHENYLPROPYLACETATE ON THE ACTION OF SUXAMETHONIUM AND OTHER NEUROMUSCULAR BLOCKING DRUGS
Authors: BELLA D. DELLA , ROGNONI F. , TEOTINO U.
Published: July 2012

On the frog rectus abdominis muscle and on sciatic nerve‐tibialis anterior muscle preparations, β‐diethylaminoethyl 3,3‐diphenylpropylacetate (SKF 525A) antagonized the actions of acetylcholine and potassium chloride as well as having an antiveratrine action. The blocking action at the skeletal neuromuscular junction of suxamethonium and its disulphonium analogue, decamethonium, tubocurarine and gallamine was enhanced by SKF 525A in the rabbit and in the isolated rat phrenic nerve‐diaphragm preparation. The activity of suxamethonium and decamethonium in the cat was reduced. On the rat phrenic nerve‐diaphragm preparation, pretreatment with SKF 525A abolished both the mutual antagonism between suxamethonium and tubocurarine and the antagonizing effect of tetraethylammonium against suxamethonium. The antagonism between tetraethylammonium and tubocurarine was unimpaired.
A NOTE ON THE ISOLATED NERVE STERNO‐TRACHEALIS PREPARATION OF THE CHICKEN
Authors: CARLYLE R. F.
Published: July 2012

A new avian neuromuscular preparation of the sterno‐trachealis muscle of the domestic chicken is described. The pharmacology of common autonomic and neuromuscular blocking drugs is given. The preparation is useful for mode of action experiments with depolarizing drugs. A short description of the anatomy is also given.
RETENTION OF INJECTED CATECHOL AMINES BY THE MOUSE
Authors: IVERSEN L. L. , WHITBY L. G.
Published: July 2012

The importance of tissue storage as a method of inactivation of circulating catechol amines has been assessed by measuring the amount of unchanged hormone remaining in the mouse 30 min after the injection of various doses of [3H]‐adrenaline or [3H]‐noradrenaline. The results show that this method of inactivation is quantitatively more important for noradrenaline than for adrenaline at all dose levels studied, and that for both hormones storage is relatively more important at physiological dose levels (3 to 30 μg/kg) than at higher dose levels (150 to 300 μg/kg). The results obtained after the simultaneous injection of various doses of [3H]‐adrenaline and [14C]‐noradrenaline show that under certain conditions the two hormones compete for entry into the tissue storage sites. The possible nature of the mechanisms by which circulating catechol amines enter the tissue stores is discussed in the light of previous findings on the uptake of catechol amines by tissues in vitro.
MECHANISM OF THE ANTAGONISM BY PRALIDOXIME AND 1,1‐TRIMETHYLENEBIS(4‐HYDROXYIMINOMETHYLPYRIDINIUM) OF THE ACTION OF ECHOTHIOPHATE ON THE INTESTINE
Authors: LEHMAN R. A.
Published: July 2012

Pralidoxime chloride (pyridine‐2‐aldoxime methochloride; Protopam Chloride) and 1,1′‐trimethylenebis(4‐hydroxyiminomethylpyridinium bromide) (TMB‐4) antagonize the spasm of the isolated or intact small intestine of the rabbit caused by the anticholinesterase, echothiophate iodide (S‐2‐dimethylaminoethyl OO‐diethyl phosphorothiolate methiodide; Phospholine Iodide). In vitro, both oximes also antagonize the spasm caused by acetylcholine. The quantitative relationships have been studied in comparison with the activity of atropine against echothiophate and acetylcholine. Echothiophate‐treated intestine which is subjected to a concentration of oxime sufficient to cause 100% restoration of function (but not cholinesterase reactivation) will go back into spasm on washing out both drugs. Strips treated with a high concentration of oxime, sufficient to cause 100% reactivation of cholinesterase, exhibit normal control tone and motility after washing. It is concluded that pralidoxime and 1,1′‐trimethylenebis(4‐hydroxyiminomethylpyridinium bromide) have an anticholinergic action as well as the ability to reactivate cholinesterase and that this action plays a significant part in the initial recovery of function under the conditions of these experiments.
EFFECT OF HEXAMETHONIUM ON THE VASCULAR RESPONSE TO NORADRENALINE IN MAN
Authors: HODGE R. L. , WHELAN R. F.
Published: July 2012

Intra‐arterial infusion of hexamethonium into the brachial artery had no potentiating effect on the constrictor response of the vessels of the forearm or hand to noradrenaline given by the same route. The response of the hand vessels to intravenous infusion of noradrenaline was enhanced after intra‐arterial hexamethonium, but this was attributed to entry of the blocking agent into the general circulation resulting in blockade of baroreceptor reflexes since the potentiation was seen to an equal degree on both sides. It is concluded that if increased sensitivity to noradrenaline plays a part in the phenomenon of tolerance to hexamethonium this must be a slowly developing effect.
CHANGES IN THE 5‐HYDROXYTRYPTAMINE CONTENT OF RAT, RABBIT AND HUMAN BRAIN AFTER DEATH
Authors: JOYCE DAPHNÉ
Published: July 2012

The fall in 5‐hydroxytryptamine concentration which occurs in brain tissues in the first 48 hr after death varies in different areas of the brain and is of the same order of magnitude in those areas of the rat and rabbit in which it was estimated, namely, hypothalamus, hippocampal gyrus and frontal cortex, and also in human frontal cortex. The loss of 5‐hydroxytryptamine is greater in the hypothalamus than in the cerebral cortex. The extent of this change depends on the temperature and conditions of storage of tissues. It is least in tissues which remain within the skull after death before chemical extraction and in tissues stored at −17° C. Comparison of cerebral 5‐hydroxytryptamine content in control animals and animals pretreated with iproniazid suggests that the differences are for the greater part due to the action of mono‐amine oxidase.
ACTIONS OF DERIVATIVES OF LYSERGIC ACID ON THE HEART OF VENUS MERCENARIA
Authors: WRIGHT ANNE McCOY , MOORHEAD MERILYN , WELSH J. H.
Published: July 2012

5‐Hydroxytryptamine and a number of (+)‐lysergic acid derivatives have been tested on the heart of Venus mercenaria. One group of derivatives was found to increase the amplitude and frequency of heart beat in a manner much like 5‐hydroxytryptamine. It included the monoethylamide, diethylamide, propanolamide (ergometrine), butanolamide (methylergometrine) and certain peptide derivatives of lysergic acid without substituents in positions 1 or 2. Of these, lysergic acid diethylamide was the most active. Given sufficient time (up to 4 hr), as little as 10 ml. of 10−16 m lysergic acid diethylamide produced a maximum increase in amplitude and frequency in about one‐half of the 80 hearts on which it was tested. Its action was very slowly reversed by washing, as was true of all lysergic acid derivatives. A second group of lysergic acid derivatives, substituted in positions 1 or 2, had weak excitor action, if any, and specific 5‐hydroxytryptamine blocking action. This group consisted of 1‐methyl‐, 1‐acetyl‐, and 2‐bromo‐lysergic acid diethylamide and 1‐methyl‐lysergic acid butanolamide (methysergide). Of these, the last showed least signs of excitor action, usually none up to 10−4 m, and it blocked 5‐hydroxytryptamine in a molar ratio of about one to one.
EFFECT OF COOLING, LOCAL ANAESTHETIC COMPOUNDS AND BOTULINUM TOXIN ON THE RESPONSES OF AND THE ACETYLCHOLINE OUTPUT FROM THE ELECTRICALLY TRANSMURALLY STIMULATED ISOLATED GUINEA‐PIG ILEUM
Authors: HARRY J.
Published: July 2012

Electrical transmural stimulation of the isolated guinea‐pig ileum preparation which was distended by an intraluminal pressure insufficient to elicit peristalsis produced two effects, one a longitudinal contraction and the other an emptying response brought about by a co‐ordinated propagated contraction of the circular muscle. The parameters of the electrical stimulus used were such that these effects were probably produced by stimulation of the nervous plexuses in the wall of the ileum. In the presence of the anticholinesterase NN‐diisopropylphosphodiamidic fluoride (Mipafox), acetylcholine was detected in the fluid passing through the lumen and also in the fluid in the organ bath. The amount was increased after a period of electrical stimulation. As variation of the frequency of stimulation from 5/min to 25/sec did not alter statistically significantly the acetylcholine output, a frequency of 5/min was used. Cooling to 13° C, the effect of local anaesthetic compounds and botulinum toxin reduced both the emptying response and longitudinal contractions of the ileum which followed transmural stimulation, with a concurrent reduction in acetylcholine output. It was concluded that the acetylcholine was released by electrical transmural stimulation from the intramural nerve plexuses in the wall of the guinea‐pig ileum.
FURTHER OBSERVATIONS ON THE DIFFERENCE IN THE METABOLISM OF HISTAMINE IN MALE AND FEMALE RATS
Authors: WESTLING H. , WETTERQVIST H.
Published: July 2012

In young rats a sex difference in the daily output of free histamine in the urine did not become apparent until after the 26th day of life, when males exhibited a lower excretion. Castration increased the urinary free histamine in male rats but had little or no effect in females. Testosterone depressed the urinary free histamine in castrated male and female rats, but did not change the excretion in intact females. When [14C]‐histamine was given by subcutaneous injection, the fraction of the dose appearing in the urine in the unchanged form followed closely the excretion of endogenous free histamine. Parallel changes were also seen in the amounts of [14C]‐histamine excreted after injection of [14C]‐(–)‐histidine. Intact male rats methylated [14C]‐histamine given by injection and [14C]‐histamine formed in the body more efficiently than did castrated males and females. Testosterone increased the degree of methylation of injected [14C]‐histamine and of [14C]‐histamine formed in the body. It is suggested that androgenic hormones increase the rate of histamine methylation in the rat and that this effect provides a satisfactory explanation for the lower excretion of urinary histamine in male rats.
EFFECT OF α‐ALKYLATED TRYPTAMINE DERIVATIVES ON 5‐HYDROXYTRYPTAMINE METABOLISM IN VIVO
Authors: GEY K. F. , PLETSCHER A.
Published: July 2012

In rats, three α‐alkylated tryptamine derivatives (α‐methyl, α‐ethyl, and αα‐dimethyltryptamine) caused alterations of 5‐hydroxytryptamine metabolism typical of monoamine‐oxidase inhibitors with short duration of action, viz., an increase of endogenous 5‐hydroxytryptamine in brain, enhancement of the increase of 5‐hydroxytryptamine in brain and heart after 5‐hydroxytryptophan administration, an inhibition of the decrease in 5‐hydroxytryptamine in brain induced by a benzoquinolizine derivative and of the increase induced by iproniazid. The increase after iproniazid was antagonized to the same extent by all the tryptamine derivatives and by harmaline, whereas dexamphetamine showed less effect. In the other experiments with brain, the tryptamine derivatives were less potent than harmaline, but somewhat more active than dexamphetamine. α‐Methyltryptamine and α‐ethyltryptamine were relatively more effective in the heart than in the brain. Among the tryptamine derivatives αα‐dimethyltryptamine had the weakest activity in brain and in heart.
MECHANISM OF THE POSITIVE INOTROPIC RESPONSES TO BRETYLIUM AND GUANETHIDINE
Authors: BHAGAT B. , SHIDEMAN F. E.
Published: July 2012

Isolated, atropinized, rat atria exhibited positive inotropic responses to bretylium, guanethidine and tyramine. These responses were prevented by treatment of the animal with reserpine, or by addition of dichloroisoprenaline to the organ bath. The positive inotropic effects of these compounds on atria from reserpinized animals were restored by incubation of the tissue with noradrenaline. On the basis of these findings it is concluded that the cardiac stimulation by bretylium, guanethidine and tyramine involves the release of catechol amines. The usually reported increase in sensitivity of the myocardium from reserpinized animals to noradrenaline was not observed. The influence of bretylium and guanethidine on cardiac uptake and release of noradrenaline was also studied with the rat. Guanethidine decreased the concentration of catechol amines and inhibited the uptake of exogenous noradrenaline, while bretylium had no effect on either. The decrease in concentration of cardiac catechol amines produced by guanethidine was prevented by treatment of the animal with bretylium or with 1‐phenyl‐2‐hydrazinopropane (pheniprazine), a monoamine oxidase inhibitor.
THE EFFECT OF ESERINE ON THE RESPONSE OF THE VAS DEFERENS TO HYPOGASTRIC NERVE STIMULATION
Authors: BURN J. H. , WEETMAN D. F.
Published: July 2012

In experiments in which the vas deferens together with the hypogastric nerve of the guinea‐pig was studied as an isolated preparation, the relation between frequency of electrical stimulation of the nerve and the height of contraction was determined. The optimal frequency was 20 shocks/sec. This value was the same when hyoscine was present to exclude the direct effect of any acetylcholine which might be released. When eserine was added to the bath in the presence of hyoscine, the response to stimulation at a frequency of 5 shocks/sec gradually increased until it became many times greater; the response to a frequency of 10 shocks/sec also increased, though to a less extent, but eserine decreased the amplitude of the contraction at a stimulus frequency of 20 shocks/sec. Neostigmine had the same effect as eserine. These findings indicate that, in the presence of hyoscine, eserine increased the noradrenaline released by low frequency stimulation, but decreased it for high frequency. If this is so, the results are compatible with the belief that there is a cholinergic link in the release of noradrenaline by hypogastric nerve stimulation.
EFFECTS OF A SINGLE EXPERIENCE ON SUBSEQUENT REACTIONS TO DRUGS
Authors: RUSHTON RUTH , STEINBERG HANNAH , TINSON CHRISTINE
Published: July 2012

The activity of rats in an unfamiliar environment was studied in order to determine how far their reactions to an amphetamine‐barbiturate mixture depended on whether or not they had been under the influence of this mixture while exposed to the same environment once before. The environment consisted of a Y‐shaped runway, and the activity studied was the number of entries into the arms of the Y during a three‐minute trial; the two trials took place three days apart. At the first trial the drug mixture practically doubled activity. At the second trial rats which had been under the influence of the drug mixture at the first trial were again made more active by the drug mixture, but the drug mixture did not increase the activity of rats which had received only saline at the first trial. These results showed that a single brief exposure to an unfamiliar environment can markedly affect subsequent reactions to drugs, and interactions of this kind may have to be taken into account when it is desired to use animals repeatedly in tests of the action of drugs on behaviour. The drug mixture also produced ataxia which was assessed quantitatively by measuring the variability of the “splay” of the rats' footprints; ataxia was unaffected by previous experience.
THE EFFECTS OF NIALAMIDE ON ADRENERGIC FUNCTIONS
Authors: DAVEY M. J. , FARMER J. B. , REINERT H.
Published: July 2012

Nialamide potentiated the pressor effects of noradrenaline in the pithed cat. In cats treated with reserpine and then pithed, it prevented the restoration of the pressor effects of tyramine by slow intravenous infusions of noradrenaline. Nialamide produced a gradual decline in the pressor effects of repeated injections of tyramine whilst the effects of tyramine on the nictitating membrane were potentiated. The development of tachyphylaxis to tyramine in the isolated guinea‐pig heart was associated with a 40% reduction in the myocardial concentration of noradrenaline. The onset of tachyphylaxis to tyramine was more rapid when nialamide was either included in the perfusion fluid or administered in vivo. Prior treatment with nialamide increased threefold the myocardial concentration of noradrenaline; however, the development of tachyphylaxis to tyramine was associated with a proportionate fall in the myocardial concentration of noradrenaline. In five out of nine experiments the acute administration of nialamide increased the output of noradrenaline per stimulus from the isolated cross‐perfused spleen of the cat when the stimulus frequency was 30 shocks/sec, but not when the frequency was 10 shocks/sec. When nialamide (20 mg/kg) was given subcutaneously to cats 20 hr before their spleens were isolated and perfused, there was a rapid fall‐off in the contractions of the spleen in response to periods of nerve stimulation. The outputs of noradrenaline per stimulus were decreased at both frequencies of stimulation. Nialamide decreased the concentrations of noradrenaline in the myocardium and spleen of the cat. The hypothesis is proposed that nialamide diminishes the availability of transmitter, as a consequence of a decreased re‐entry of noradrenaline into a storage site present in nerve endings, and that such a decrease in the availability of noradrenaline in hyperactive nerve pathways may account for the antihypertensive effects of monoamine oxidase inhibitors in man.
THE CHOLINERGIC BLOCKING ACTION OF ADRENERGIC BLOCKING AGENTS IN THE PHARMACOLOGICAL ANALYSIS OF AUTONOMIC INNERVATION
Authors: BOYD HELEN , BURNSTOCK G. , CAMPBELL G. , JOWETT ALISON , O'SHEA JUDITH , WOOD MARGARET
Published: July 2012

The adrenergic blocking agents tolazoline, phentolamine, piperoxan, yohimbine, phenoxybenzamine, bretylium and guanethidine block the excitatory actions both of cholinergic nerves and of added acetylcholine on a variety of vertebrate smooth muscle preparations. These cholinergic blocking actions often occurred with concentrations lower than those required to block the response of the guinea‐pig vas deferens to stimulation of the adrenergic hypogastric nerve. The anti‐acetylcholine activities of these drugs have been studied in detail, using the guinea‐pig rectum and the toad bladder as test organs. In preparations sensitive to eserine, the anticholinesterase actions of the drugs competed with their anti‐acetylcholine actions, so that either potentiation or block of responses to acetylcholine and to cholinergic nerve stimulation occurred with different concentrations. The responses of the toad bladder to acetylcholine were not potentiated by eserine. This enabled the antagonism of acetylcholine by the anti‐adrenergic drugs to be estimated without interference from their anticholinesterase activity. When blocking activity was assessed on guinea‐pig rectum previously treated with dyflos, the results were qualitatively similar to those on the toad bladder. Phenoxybenzamine often completely blocks responses both to added acetylcholine and to cholinergic nerve stimulation in concentrations less than those required to block adrenergic nerves. Guanethidine and piperoxan also show strong cholinergic blocking activity. Bretylium, yohimbine, tolazoline and phentolamine were less potent. However, in concentrations required to block the effect on the vas deferens of hypogastric nerve stimulation, these drugs at least halved the effects of acetylcholine and often of cholinergic nerve stimulation. It is concluded that these adrenergic blocking agents cannot be used to distinguish conclusively between adrenergic and cholinergic nerves. For reliable analysis of autonomic innervation, the substances released upon nerve stimulation must be identified by specific biochemical techniques or bioassay.
ANTAGONISM OF ACETYLCHOLINE BY ADRENALINE ANTAGONISTS
Authors: BENFEY B. G. , GRILLO S. A.
Published: July 2012

Phenoxybenzamine antagonized the inhibitory action of acetylcholine on the guineapig isolated atrium. The antagonism was slow in onset, very slowly reversible, and could be overcome by increased concentrations of acetylcholine. In contrast, atropine inhibited the action of acetylcholine quickly, and the effect disappeared soon after withdrawal. The pA10 of phenoxybenzamine (2 hr of contact) was 6.8, and that of atropine (30 min of contact) was 8.4. In the presence of atropine phenoxybenzamine did not exert a slowly reversible antagonism, and the dose‐ratio of acetylcholine returned to normal soon after withdrawal of both drugs. Phenoxybenzamine also antagonized acetylcholine in the guinea‐pig isolated ileum, but with higher concentrations acetylcholine did not overcome the antagonism. The pA10 (60 min of contact) was 6.6. The pA10 of chlorpromazine in the atrium (2 hr of contact) and ileum (60 min of contact) was 5.9. Phentolamine, 2‐diethylaminomethylbenzo‐1,4‐dioxan hydrochloride (883 F), and yohimbine antagonized acetylcholine in the atrium and ileum but required higher concentrations than chlorpromazine.
THE RELATION BETWEEN UROGASTRONE AND GONADOTROPHINS
Authors: PERERA B. A. V. , ROSENOER V. M.
Published: July 2012

A commercial preparation of chorionic gonadotropin inhibited gastric acid secretion induced by carbachol in rats. When the preparation was incubated for 10 min at 100° C and pH 7, its gonadotrophic activity, as measured by a simple quantal assay based on the male toad spermiation response, was reduced by 92%. The inhibition of gastric acid secretion by the preparation was not significantly reduced by this treatment. It is concluded that the two activities are separable.
THE EFFECTS OF GANGLION‐BLOCKING AND POSTGANGLIONIC SYMPATHOLYTIC DRUGS ON PREPARATIONS OF THE GUINEA‐PIG VAS DEFERENS
Authors: BENTLEY G. A. , SABINE J. R.
Published: July 2012

The contractions of the guinea‐pig isolated vas deferens elicited by electrical stimulation of the hypogastric nerve were completely blocked by the following drugs: guanethidine, bretylium, dimethylphenylpiperazinium hydrochloride, nicotine, pempidine, hexamethonium, hemicholinium, d‐tubocurarine and procaine. However, when the vas deferens was stimulated through an electrode in its lumen, the contractions in response to frequent, short stimuli (50 shocks/sec, 1 msec duration) were blocked by guanethidine, bretylium and dimethylphenylpiperazinium, but were not affected by the remaining drugs, except that procaine and hemicholinium each caused some reduction in the responses. When the preparation was stimulated transmurally with shocks of 200 msec duration at 1 shock/sec, the contractions were unaffected by any of the above drugs, except hemicholinium which again caused a slow reduction of up to 50% of the original response. It is concluded that nicotine, pempidine, hexamethonium, d‐tubocurarine and hemicholinium probably block the response to stimulation of the hypogastric nerve by acting on peripheral ganglia in its pathway. Hemicholinium appears to have an additional effect in depressing the responses of the smooth muscle of the vas deferens to direct electrical stimulation, and procaine may act both on the ganglia and at the nerve terminals.
SOME EFFECTS OF ATROPINE ON SMOOTH MUSCLE
Authors: CUTHBERT A. W.
Published: July 2012

Contractions of the nerve‐free smooth muscle of the chick amnion, either spontaneous or in response to electrical or mechanical stimuli, are potentiated by high concentrations (10−5 g/ml.) of atropine sulphate. In addition hyoscine, homatropine, lachesine, propantheline bromide and atropine N‐methyl and atropine N‐butyl salts potentiate spontaneous activity in the amnion. The effects of atropine do not appear to depend on inhibition of cholinesterase; on labilization, stabilization or depolarization of the muscle cell membrane; or on an increase in metabolism. It is suggested that the effects are the result of blockade of the muscarinic acetylcholine receptors. The way in which this may facilitate the conducted response is discussed.
POTENTIATION OF SOME CATECHOL AMINES BY PHENOXYBENZAMINE, GUANETHIDINE AND COCAINE
Authors: STAFFORD ANNE
Published: July 2012

In rabbit isolated atria, cocaine, guanethidine and phenoxybenzamine increased the changes in rate and force of contractions caused by noradrenaline and adrenaline, but did not potentiate isoprenaline. The most likely explanation for this result is that the drugs interfere with one of the mechanisms in the heart by which noradrenaline and adrenaline, but not isoprenaline, are inactivated; a probable mechanism would be the uptake of noradrenaline into storage sites in the tissue. Cocaine, guanethidine and phenoxybenzamine did not potentiate noradrenaline and adrenaline acting on the rabbit isolated duodenum and the rat uterus.
A COMPARISON OF THE ANTIFIBRILLATORY ACTIONS AND EFFECTS ON INTRACELLULAR CARDIAC POTENTIALS OF PRONETHALOL, DISOPYRAMIDE AND QUINIDINE
Authors: SEKIYA A. , WILLIAMS E. M. VAUGHAN
Published: July 2012

A quantitative comparison of the effects of quinidine, pronethalol and γ‐di‐iso‐propylamino‐α‐phenyl‐α‐pyrid‐2‐ylbutyramide (disopyramide) has been made on rabbit isolated atria. All three drugs raised the electrical threshold and reduced the contractions, the conduction velocity and the maximal frequency at which the atria would follow a stimulus. The descending order of potency was pronethalol, quinidine and disopyramide, but the range was small, pronethalol having about twice the activity of disopyramide. Both the new compounds affected intracellular potentials in the same way as quinidine, causing little change in the resting potential or duration of the action potential, but reducing the overshoot potential and slowing the rate of rise of the action potential. These results support the view that interference with depolarization is an essential feature of antifibrillatory activity.
A STABLE SUBSTRATE FOR THE ASSAY OF PLASMA KININ‐FORMING ENZYMES
Authors: AMUNDSEN E. , NUSTAD K. , WAALER B.
Published: July 2012

A substrate plasma for estimation of plasma kinin‐forming enzyme activity in biological fluids has been prepared from human blood. Fresh citrated plasma was treated by a brief contact with a large amount of silicate powder, followed by heating to 56° C for 1 hr, and finally by lowering its pH to 2 for 10 min. As an alternative to the final treatment with acid, disodium edetate was added to the plasma. The resulting final plasma did not show “spontaneous” plasma kinin activity on contact with glass, contained no kininase activity and did not inhibit plasma kinin enzyme activity of added specimens. The content of plasma kinin precursor in this final plasma was such that it could yield an amount of plasma kinin which corresponded to between 1 and 4 μg of synthetic bradykinin/ml.
THE ACTION OF THE TOXIN OF PRYMNESIUM PARVUM CARTER ON THE GUINEA‐PIG ILEUM
Authors: BERGMANN F. , PARNAS I. , REICH K.
Published: July 2012

The ichthyotoxin from Prymnesium parvum caused a slow contraction of the guinea‐pig isolated ileum preparation, followed by decreased sensitivity to acetylcholine and to 5‐hydroxytryptamine. These effects were reversed by washing. Administration of toxin was followed by insensitivity to further toxin. It was possible that a cholinergic transmitter participated in the contractions of the gut as this action was reduced both by atropine and by morphine. Illumination with visible light or warming a solution of toxin destroyed its antiacetylcholine activity before abolishing its stimulant action on gut. The crude extract of Prymnesium parvum may contain a mixture of active substances with different pharmacological actions.
SOME OBSERVATIONS ON THE PHARMACOLOGY OF α‐METHYLDOPA
Authors: DAY M. D. , RAND M. J.
Published: July 2012

α‐Methyldopa in high concentrations impaired the responses of rabbit isolated ileum and guinea‐pig isolated vas deferens to stimulation of the sympathetic nerves and to noradrenaline, but these preparations taken from animals previously treated with α‐methyldopa showed no sign of impairment. Contractions of the cat nictitating membrane were reduced but not abolished by α‐methyldopa. In cats, dogs and rats, pressor responses to noradrenaline were usually slightly increased by α‐methyldopa. Pressor responses to tyramine were not affected consistently. α‐Methyldopa, α‐methyldopamine and α‐methylnoradrenaline behaved like dopa, dopamine and noradrenaline respectively in restoring the responses of tissues from reserpine‐treated animals to stimulation of the sympathetic nerves to the rabbit ileum, the guinea‐pig vas deferens and the cat nictitating membrane and in restoring responses to tyramine of the cat blood pressure and nictitating membrane, and the rat blood pressure. The potency of α‐methylnoradrenaline relative to noradrenaline ranged from one‐half to one‐ninth on various preparations. The results are discussed in relation to the anti‐hypertensive action of α‐methyldopa.
OBSERVATIONS ON THE SIGNIFICANCE OF 5‐HYDROXYTRYPTAMINE IN RELATION TO THE PERISTALTIC REFLEX OF THE RAT
Authors: BOULLIN D. J.
Published: July 2012

Peristalsis of normal rats, and of rats fed either on a control diet or on a tryptophan‐free diet (5‐hydroxytryptamine‐depleted rats), was studiedin vitroandin situto test the hypothesis that 5‐hydroxytryptamine functions as a local hormone in the intestine and may be essential for initiation of the peristaltic reflex. A tryptophan‐free diet depleted intestinal 5‐hydroxytryptamine by a mean value of 90% in some rats, the depletion appeared to be complete. Peristaltic responses, even of rats with complete depletion, were qualitatively similar to, and quantitatively not statistically different from those of normal or of pair‐fed control animals whose intestinal mucosa contained high concentrations of 5‐hydroxytryptamine. Intraluminal and serosal 5‐hydroxytryptamine produced effects in 5‐hydroxytryptamine‐depleted rats similar to those in the normal and in the control animals. Furthermore, the maximal stimulatory effects of 5‐hydroxytryptamine on peristaltic performance were not greater than spontaneous variations in performance in any group of animals, except with tryptophan‐fed control rats, when the effects of the amine on peristalsisin situwere greater than spontaneous variation. It was therefore concluded that 5‐hydroxytryptamine is not essential for peristalsis in the rat.
THE RESPIRATORY ACTION OF DICHLORPHENAMIDE
Authors: DOYLE D. , HARRIS E. A. , SLAWSON K. B.
Published: July 2012

The action of dichlorphenamide has been investigated in three healthy subjects. After this drug had been given, ventilation increased while alveolar and oxygenated mixed venous Pco2 both fell. The magnitude of these changes was closely related to the degree of acidosis produced by the drug. The effect of intravenous acetazol‐amide, tested in one subject, was qualitatively similar to that of orally administered dichlorphenamide. Respiratory responses to carbon dioxide were studied in two of the subjects and in one of them the metabolic acidosis was sufficient to account for the short‐term effect of dichlorphenamide on respiration.
RELEASE OF “NEUROKININ” ON NERVOUS AND ELECTRICAL STIMULATION OF A FROG STOMACH MUSCLE PREPARATION
Authors: SINGH I.
Published: July 2012

Activation of a frog stomach muscle preparation by electrical stimulation of a vagus nerve or by direct stimulation released two polypeptides. One was destroyed by trypsin or chymotrypsin in about 10 min; the activity of the other was enhanced by trypsin for about 10 min, but was destroyed by chymotrypsin. Similar stimulation of dog stomach muscle did not release these polypeptides. Correspondingly, the transmission from vagus nerve to stomach muscle in the frog was resistant to atropine, but was blocked by atropine in the dog.
Role of the chemoreceptor trigger zone in histamine‐induced emesis
Authors: BHARGAVA K. P. , DIXIT K. S.
Published: July 2012

. In unanaesthetized dogs, the emetic action of histamine was studied after its injection into the cerebral venricles through chronically implanted cannulae in order to elucidate the role of the chemoreceptor trigger zone (CT‐zone), situated in the area postrema, for this emesis.

. On injection into the lateral cerebral ventricle, about 10 times larger doses of histamine (3 mg) were required regularly to produce emesis, and it occurred after a longer latency than on injection into the fourth ventricle. This is in accord with an action of histamine on the CT‐zone.

. After bilateral ablation of the CT‐zone, intraventricular injections of histamine no longer produced emesis even when injected in doses which were three to four times greater than those which regularly elicited vomiting in dogs with intact CT‐zone. The emesis produced in dogs by intraventricular injections of histamine is thus fully accounted for by an action on the CT‐zone.

. Injections of chlorpromazine intramuscularly or of the two antihistamines cyclizine and mepyramine, either intramuscularly or into the lateral ventricle, prevented the emesis caused by histamine injected into the lateral ventricle. This protective action of the antihistamines—which did not extend to the emesis produced by oral copper sulphate—suggests the presence of histaminergic receptors in the CT‐zone.
The release of 3H‐dopamine from the isolated rabbit ileum
Authors: COLLINS G. G. S. , WEST G. B.
Published: July 2012

. Segments of rabbit ileum incubated with 3H‐DOPA or 3H‐dopamine and perfused with McEwen solution spontaneously release 3H‐dopamine; this basal release is doubled when the sympathetic nerves are stimulated. Evidence is presented to show that the release is probably from the sympathetic nerve terminals.

. Both cocaine and bretylium reduce the spontaneous release of 3H‐dopamine as well as the increased release resulting from sympathetic nerve stimulation. Guanethidine depresses the release during nerve stimulation but increases the spontaneous release of the amine. Phenoxybenzamine potentiates both the spontaneous release and that during nerve stimulation.

. Tyramine releases 3H‐dopamine from the preparation but tachyphylaxis to the drug rapidly develops.

. It is concluded that the release of 3H‐dopamine from the sympathetic nerves of the isolated perfused rabbit ileum possesses many of the characteristics of that of noradrenaline from other sympathetically innervated structures.
Isolated 5‐hydroxytryptamine organelles of rabbit blood platelets: physiological properties and drug‐induced changes
Authors: DA PRADA M. , PLETSCHER A.
Published: July 2012

. In isolated 5‐hydroxytryptamine (5‐HT) organelles of rabbit platelets, the concentrations of 5‐HT, histamine and adenosinetriphosphate (ATP) respectively are about 200 times higher than in intact platelets. Organelles incubated in plasma at 37° C gradually lose endogenous 5‐HT, histamine and ATP and take up 14C‐5‐HT against a considerable concentration gradient. Liberation and uptake of 5‐HT markedly decrease with dimishing incubation temperature.

. Exposure to reserpine in vitro strongly counteracts the uptake of 14C‐5‐HT by isolated organelles, whereas the 14C‐5‐HT uptake of intact isolated platelets is less affected by the drug. 5‐HT organelles of platelets from reserpinized rabbits also take up very little 14C‐5‐HT.

. Imipramine inhibits the uptake of 14C‐5‐HT in isolated organelles less markedly than in isolated platelets.

. It is concluded that in the organelles 5‐HT and possibly histamine may be associated with ATP. Reserpine probably impairs the uptake of 5‐HT at the level of the organelles (possibly by interfering with the association 5‐HT/ATP), whereas imipramine seems to act preferentially on the cell membrane.
The potentiation of rat uterine inhibitory responses to noradrenaline by theophylline and nitroglycerine
Authors: LEVY B. , WILKENFELD B. E.
Published: July 2012

. Dose response curves for noradrenaline were determined before, during and after pretreatment with a variety of agents. The inhibitory response to noradrenaline on the isolated rat uterus was measured according to its ability to inhibit an acetylcholine induced contraction.

. Theophylline, an agent that inhibits phosphodiesterase and increases cyclic AMP levels in the rat, potentiated the response to noradrenaline.

. Pretreatment with cocaine had no significant effect on the potentiation of the noradrenaline response by theophylline.

. Theophylline potentiated the inhibitory response to nitroglycerine.

. Pretreatment with nitroglycerine also potentiated the inhibitory response to noradrenaline.

. Theophylline appears to produce a potentiation of the inhibitory effect of noradrenaline on the rat uterus by means of a non‐specific mechanism.