bluuebunny/crossref_metadata_2025 huggingface dataset:
THE EFFECTS OF ION CHANGES ON THE CONTRACTION OF THE RAT UTERUS STIMULATED BY OXYTOCIN
Authors: BENTLEY P. J. , McEWEN ELEANOR
Published: July 2012

The contraction of the rat uterus to oxytocin was measured when it was bathed in various solutions. Substitution of nitrate or bromide for two‐thirds of the chloride present increased the size of contractions, while a similar substitution of sulphate and sucrose for chloride depressed them. Alteration of the ratio of chloride to sodium by substitution of choline for two‐thirds of the sodium present enhanced the contractions, but this was probably due to the choline per se as choline sulphate similarly enhanced the response. Partial replacement of both sodium and chloride by sucrose did not alter the size of contractions.
FACTORS INFLUENCING THE HYPERTENSIVE EFFECT OF ESERINE IN THE RAT
Authors: LEŠIĆ R. , VARAGIĆ V.
Published: July 2012

Several factors influencing the hypertensive effect of eserine in the rat were investigated. Pretreatment with reserpine regularly depressed or abolished the hypertensive response to eserine. The slow intravenous infusion of either noradrenaline, dihydroxyphenylalanine or 5‐hydroxytryptamine only occasionally restored the hypertensive effect of eserine in reserpine‐treated rats. Bretylium and choline 2,6‐xylyl ether bromide significantly depressed or even abolished the hypertensive effect of eserine. The effect of bretylium was stronger than that of choline 2,6‐xylyl ether bromide. Cocaine was found to antagonize the action of bretylium on the response to eserine. In doses which significantly depressed the action of eserine bretylium did not inhibit the hypertension due to excitation of medullary centres induced by clamping the common carotid arteries. Lowering of body temperature abolished the hypertensive effect of eserine. Pretreatment with isopropylisoniazid did not antagonize the inhibitory action of reserpine on the hypertensive response to eserine. It is concluded that the present experiments indicate that the hypertensive effect of eserine in the rat is due to central activation of adrenergic nervous elements. Liberation of noradrenaline (and adrenaline) from the adrenals and from the blood vessels by eserine is an insignificant factor in producing the hypertensive response to eserine.
SOME BIOLOGICAL PROPERTIES OF CEPHALOSPORIN C AND A DERIVATIVE
Authors: JAGO M. , HEATLEY N. G.
Published: July 2012

Some biological properties of cephalosporin C and of a pyridinium derivative, “cephalosporin CA (pyridine),” were examined. Staphylococci, both penicillinase‐producing and non‐penicillinase‐producing, and some other bacteria tested, were inhibited by 60 to 125 μg cephalosporin C/ml., and 5 to 20 μg cephalosporin CA (pyridine)/ml. The ratio of the activity of the two antibiotics varied for different organisms. Resistance developed slowly on repeated subculture of penicillinase‐producing staphylococci in presence of either antibiotic. The minimum inhibitory concentration of cephalosporin CA (pyridine) upon penicillinase‐producing staphylococci increased 4 to 8‐fold with a 500‐fold increase in inoculum size; with cephalosporin C there was a 2‐fold increase. Their activity was not reduced by serum. Both substances were non‐toxic. They were excreted quantitatively in the urine when given intravenously or subcutaneously to mice. After oral administration less than 5% of the dose was excreted. Cephalosporin CA (pyridine) was about 8 times more active than cephalosporin C in protecting mice from an experimental streptococcal infection, nine doses of 6.25 mg/kg affording complete protection.
FATE OF SYNTHETIC OXYTOCIN ANALOGUES IN THE RAT
Authors: SMITH M. W. , GINSBURG M.
Published: July 2012

The disappearance of phe3‐oxytocin, val3‐oxytocin and oxytocin from the circulation of male rats was shown to be due to qualitatively similar mechanisms, that is, it depends on uptake in the kidneys and organs of the splanchnic vascular area. However, compared to phe3‐oxytocin and oxytocin (whose half‐lives were essentially similar) val3‐oxytocin took twice as long to reach half its initial blood concentration. In lactating rats the mammary glands probably participated in the uptake of phe3‐oxytocin, but the rate of disappearance of val3‐oxytocin was not different from that in non‐lactating animals. In male nephrectomized rats without splanchnic circulation, phe3‐oxytocin, unlike val3‐oxytocin, was quickly distributed in a volume equal to two‐thirds of the total body water. Using oxytocin as the standard, val3‐oxytocin and phe3‐oxytocin were more potent when assayed on a superfused uterus or on a rat uterus in vivo than when assayed by the pharmacopoeial method (1958) on the isolated uterus in an organ bath. The difficulties of assaying oxytocin analogues against oxytocin (or the international standard preparation) are discussed.
EFFECTS OF 5‐HYDROXYTRYPTAMINE ON THE DORSAL MUSCLE OF THE LEECH (HIRUDO MEDICINALIS)
Authors: SCHAIN R. J.
Published: July 2012

5‐Hydroxytryptamine has an inhibiting effect on the leech muscle. It reduces the contractions produced by acetylcholine or nicotine and accelerates the relaxation of the muscle when these substances are washed out. This acceleration of relaxation allows a more rapid assay of acetylcholine in this preparation.
THE EFFECT OF MEPHENTERMINE ON ISOLATED DOG HEARTS, NORMAL AND PRETREATED WITH RESERPINE
Authors: FAWAZ G.
Published: July 2012

The inotropic activity of the non‐catechol sympathomimetic amine, mephentermine sulphate, on the failing dog heart‐lung preparation, was 1/10 to 1/20 that of adrenaline. Mephentermine showed no inotropic effect on preparations from animals pretreated with reserpine. The chronotropic and “calorigenic” actions of mephentermine were tested on modified heart‐lung preparations to permit a more accurate measurement of coronary flow, and were found to be greater than its inotropic effect relative to adrenaline. Furthermore, the action of mephentermine was longerlasting than that of adrenaline. If adrenaline was infused 15 min after the termination of mephentermine administration and when the action of the latter was still at a maximum, a further increase in heart rate and especially oxygen consumption was observed. In preparations from dogs treated with enough reserpine to deplete the heart of noradrenaline, mephentermine had only slight chronotropic and calorigenic actions. However, further addition of adrenaline after a 15 min pause caused a rise in heart rate, oxygen consumption, and coronary flow which almost duplicated the additive effects of both amines on the preparations not treated with reserpine. It would appear that adrenaline acted on its own and in addition “restored” the action of mephentermine on the reserpinized preparations. The action of adrenaline alone on reserpinized preparations was not increased compared with that on normal preparations. These observations are relevant to a consideration of the mechanism of action of non‐catechol sympathomimetic amines on the heart, and are in harmony with the concept that mephentermine, a non‐catechol amine, requires the presence of added or stored catechol amines for its action. Reserpine treatment did not alter the mechanical efficiency of the heart despite its depletion of noradrenaline.
POTENTIATION OF INHIBITORY AND EXCITATORY EFFECTS OF CATECHOL AMINES BY BRETYLIUM
Authors: GOKHALE S. D. , GULATI O. D.
Published: July 2012

Enhancement of both excitatory and inhibitory responses to adrenaline, noradrenaline and isoprenaline was demonstrated with bretylium both in vivo and in vitro. Excitatory responses studied included rise of blood pressure and contraction of the nictitating membrane in cats and the contraction of aortic strip in rabbits; the inhibitory responses studied were fall of cat blood pressure and relaxation of rat uterus and rabbit tracheal chain. Possible mechanisms of potentiation of the effects of catechol amines by bretylium are discussed. A sensitization of the peripheral effector cells is suggested as a likely mechanism of potentiation.
STUDIES ON THE SLOW CONTRACTION OF SMOOTH MUSCLE PRODUCED BY HUMAN PLASMA
Authors: GABR Y.
Published: July 2012

The slow contraction of smooth muscle produced by human plasma becomes less potent after storage of the plasma for six months at room temperature and after processing of the plasma with kaolin. These observations fall into line with the fact that 40% of the initial smooth‐muscle‐contracting activity of the plasma can be accounted for in the deposit which is formed during the six‐months period of storage, and also with the fact that the recovery of G acid from human plasma treated with kaolin is about 50% of the yield which is obtained from the same plasma before kaolin treatment.
EFFECT OF RESERPINE ON THE 5‐HYDROXYTRYPTAMINE AND ADENOSINETRIPHOSPHATE OF THE DOG INTESTINAL MUCOSA
Authors: PRUSOFF W. H.
Published: July 2012

Homogenates were prepared of the mucous membrane of the small intestine from dogs previously treated with high doses of reserpine. The granular material sedimented from these homogenates was centrifuged over a density gradient. The dense fraction usually rich in adenosinetriphosphate and 5‐hydroxytryptamine contained little amine and no nucleotide; on the other hand, the less dense material, believed to consist mainly of mitochondria, contained amounts of adenosinetriphosphate similar to those found in animals not treated with reserpine.
THE DISTRIBUTION OF SOME QUATERNARY AMMONIUM SALTS IN THE PERIPHERAL NERVOUS SYSTEM OF CATS IN RELATION TO THE ADRENERGIC BLOCKING ACTION OF BRETYLIUM
Authors: BOURA A. L. A. , DUNCOMBE W. G. , McCOUBREY A.
Published: July 2012

The concentrations of bretylium in the peripheral nervous system of cats after subcutaneous dosage have been compared with those drugs bearing either chemical or pharmacological resemblance to bretylium. o‐Bromobenzyltrimethylammonium iodide (383C57), a chemical homologue of bretylium with feeble adrenergic blocking activity, selectively accumulated in adrenergic neurones to attain concentrations comparable with those found for bretylium, but it did not persist in the neurones. {2‐(4‐Benzoyl‐2,6‐dimethylphenoxy)ethyl} trimethylammonium, the 4‐benzoyl derivative of 2,6‐xylyl choline ether (172C58), a pharmacological analogue of bretylium but with little chemical resemblance, had a less marked selective affinity for adrenergic neurones and the concentrations after an effective dose were much lower than found for bretylium. Pentacynium {N1‐5‐cyano‐5,5‐diphenylpentyl)‐N1N1N2‐trimethylethylene‐1‐ammonium‐2‐morpholinium di‐iodide}, a bis‐quaternary ammonium‐type ganglion blocking agent, had no selective affinity for adrenergic neurones. Bretylium was not displaced from adrenergic neurones by a subsequent dose of 172C58. The potency and duration of local anaesthetic action of bretylium, 383C57 and 172C58 were roughly parallel to the potency and duration of their adrenergic blocking action. The results are discussed in relation to the role of selective accumulation in adrenergic neurones by bretylium in its adrenergic blocking activity.
A NOTE ON THE DISTRIBUTION OF [14C]‐HISTAMINE ADDED TO BLOOD
Authors: LINDELL S.‐E. , VISKE K.
Published: July 2012

14C‐Labelled histamine was incubated with canine or human blood at 37° C. After 1 hr 80 to 100% of the added histamine could be recovered in unchanged form. When [14C]‐histamine was added to whole blood in vitro it tended to become equally distributed between the cell and plasma fraction of the blood, and when the cell fraction of blood containing [14C]‐histamine was suspended in [14C]‐histamine‐free plasma the labelled histamine tended to become equally distributed between cells and plasma. The pattern of distribution of intravenously injected [14C]‐histamine in the blood of anaesthetized dogs seemed to be the same as that of histamine added in vitro. The injected histamine entered the cell fraction of the blood at a slow rate. These experiments indicate that in dog and man the blood cells are of little or no importance for the inactivation of histamine released into the circulating blood.
STRESS‐INDUCED BLOCK OF MILK EJECTION
Authors: CHAUDHURY R. R. , CHAUDHURY M. R. , LU F. C.
Published: July 2012

A simple method has been described by which the action of drugs on the stress‐induced block in milk ejection can be investigated on lactating guinea‐pigs. Reserpine, meprobamate and chlorpromazine when administered to the lactating mother at various periods before suckling reduced the block in milk ejection caused by the stress. Dibenamine and dichloroisoprenaline did not affect in any way the stress‐induced block. It is suggested that the stress‐induced block in milk ejection is probably a nervous block and not mediated through adrenaline.
EFFECTS OF COCAINE AND ANTIDEPRESSANT DRUGS ON THE NICTITATING MEMBRANE OF THE CAT
Authors: RYALL R. W.
Published: July 2012

Cocaine, imipramine and pipradol potentiated the contractions to adrenaline and noradrenaline, but not to tyramine, on the nictitating membrane of the spinal cat. Pheniprazine and dexamphetamine potentiated the responses to adrenaline, noradrenaline and tyramine, whereas nialamide only potentiated the response to tyramine. Potentiation of the response to stimulation of either the preganglionic or the postganglionic sympathetic nerve trunks was observed with imipramine, pipradol, pheniprazine and dexamphetamine. Only dexamphetamine and pheniprazine caused substantial contractions of the membrane when the preganglionic nerve was cut (acutely decentralized), or when the superior cervical ganglion was removed (acutely denervated). Cocaine produced contractions of the innervated but not of the acutely decentralized membrane. The significance of the peripheral effects of these antidepressant drugs in relation to their central actions is discussed.
ACTION OF BRETYLIUM AND GUANETHIDINE AT THE NEUROMUSCULAR JUNCTION
Authors: DIXIT B. N. , GULATI O. D. , GOKHALE S. D.
Published: July 2012

Bretylium and guanethidine produced a block of neuromuscular transmission in the rat phrenic nerve diaphragm and cat sciatic gastrocnemius preparations, but had a potentiating effect on acetylcholine‐induced contracture of the frog rectus. On the sciatic gastrocnemius preparation of the cat the compounds had a twofold action, consisting of an initial transient, and a delayed but more sustained, block of neuromuscular transmission. Bretylium and guanethidine had no immediate effect on the response of the muscle to direct stimulation, though a weak delayed depressant effect was observed. Intravenous injection of these compounds produced a flaccid paralysis in pigeons. Possible mechanisms of the neuromuscular blocking action of bretylium and guanethidine are discussed. Inhibition of acetylcholine release from motor nerve endings resulting from local anaesthesia by these compounds is suggested as a possible mechanism of their neuromuscular blocking action.
ANTI‐TRYPANOSOMAL ACTIVITY OF CERTAIN PHENYLDIAZOAMINO‐ AND PHENYLAZOAMINO‐PHENANTHRIDINIUM COMPOUNDS
Authors: BROWN K. N. , HILL J. , HOLLAND A. E.
Published: July 2012

Red phenyldiazoaminophenanthridinium and purple phenylazoaminophenanthridinium compounds, most of which were obtained as isomeric pairs, were tested in mice for curative and prophylactic action against Trypanosoma congolense. Several of the individual compounds showed a high degree of activity, the red isomer of each pair usually being more active therapeutically and prophylactically than the purple one, although high prophylactic effect was not always associated with high therapeutic potency. The most interesting isomeric pair was that consisting of metamidium, 7‐(m‐amidinophenyldiazoamino)‐2‐amino‐10‐ethyl‐9‐phenylphenanthridinium chloride hydrochloride (red isomer) and x‐(m‐amidinophenylazo)‐2,7‐diamino‐10‐ethyl‐9‐phenylphenanthridinium chloride hydrochloride (purple isomer). Among the individual compounds, the one with the greatest curative action was the red isomer of metamidium, now known as isometamidium. Its 10‐methyl homologue was slightly less active and its p‐amidino‐isomer was considerably less active. The compounds with the greatest prophylactic action were 2,7‐di(m‐amidinophenyldiazoamino)‐10‐ethyl‐9‐phenylphenanthridinium chloride dihydrochloride trihydrate, its 10‐methyl homologue, and the red m‐amidino‐isomers mentioned above. The only other compounds to show appreciable prophylactic action were three guanidino‐substituted phenyldiazoaminophenanthridines, although they were less active than metamidium at low doses. One of these, 2‐amino‐10‐ethyl‐7‐(m‐guanidinophenyldiazoamino)‐9‐phenylphenanthridinium chloride hydrochloride, was also very active therapeutically.
A COMPARISON OF TESTS FOR ANTIFIBRILLATORY ACTION
Authors: WILLIAMS E. M. VAUGHAN , SZEKERES L.
Published: July 2012

The object of the experiments was twofold: first, to choose the most satisfactory test for antifibrillatory action; secondly, to place several drugs with reputed anti‐fibrillatory activity in an order of potency as a preliminary to investigating their mode of action. Measurements were made on isolated rabbit atria at 34° C of (1) the maximum driving frequency the atria would follow, (2) conduction velocity, (3) contractions, and of the threshold for the production of (4) extrasystoles, (5) flutter and (6) fibrillation. Log dose‐response curves were plotted for quinidine, papaverine, procaine, dibenamine and procaine amide. The maximum frequency test and fibrillation threshold test gave similar results with all the drugs, and the results gave the order quinidine 1.0, procaine 0.53, Dibenamine 0.47, papaverine 0.43 and procainamide 0.26. Thresholds for extrasystoles and flutter were much more variable. The regressions relating changes in conduction velocity and contraction to log dose were different from those for maximum driving frequency and fibrillation threshold for procaine, papaverine and dibenamine, but the regressions for quinidine and procaine amide were nearly parallel in all tests. Serpajmaline contained a substance with anti‐fibrillatory activity as great as that of quinidine and with no greater depressant action on contractions.
ON THE QUESTION OF THE OCCURRENCE AND METABOLISM OF 5‐HYDROXYTRYPTAMINE AND RELATED INDOLE COMPOUNDS IN MAMMALIAN SEMEN
Authors: MANN T. , SEAMARK R. F. , SHARMAN D. F.
Published: July 2012

The content of 5‐hydroxytryptamine was examined in the semen of man, bull, ram, boar and dog. Spectrophotofluorimetric and chromatographic analysis of extracts prepared by several methods has shown that the semen contains only minute quantities of 5‐hydroxytryptamine, if any. One cannot attribute to 5‐hydroxytryptamine the uterus‐stimulating effect which the human seminal plasma is known to exert. Tryptophan, although present in the seminal plasma, is not converted to 5‐hydroxytryptamine on incubation of semen. 5‐Hydroxytryptophan is oxidatively deaminated, but not decarboxylated, by spermatozoa. 5‐Hydroxytryptamine itself, like tryptamine and tyramine, is not deaminated by either whole semen or washed suspensions of ram spermatozoa.
EFFECT OF 5‐HYDROXYTRYPTAMINE ON THE RESPIRATION OF EXCISED LAMELLIBRANCH GILL
Authors: MOORE K. E. , MILTON A. S. , GOSSELIN R. E.
Published: July 2012

5‐Hydroxytryptamine, but not acetylcholine or catecholamines, stimulated the endogenous respiration of the excised gills of Modiolus demissus and Mytilus edulis. Respiratory stimulation by 5‐hydroxytryptophan is presumed to have occurred only after it had been decarboxylated to 5‐hydroxytryptamine. 2‐Bromolysergic acid diethyl‐amide inhibited the effect of 5‐hydroxytryptamine, while lysergic acid diethylamide mimicked it. The glycogen that was degraded during incubation of the gill cannot account for all of the oxygen that was consumed, indicating that some other substrate within the gill was also oxidized. That the metabolic actions of 5‐hydroxytryptamine may be related to its cilio‐acceleratory activity is discussed.
ANTIHISTAMINE ACTIVITY IN EXTRACTS OF HORSE EOSINOPHILS
Authors: ARCHER R. K. , FELDBERG W. , KOVACS B. A.
Published: July 2012

Suspensions of horse eosinophils or the watery extracts of such suspensions were injected intraperitoneally into guinea‐pigs. The eosinophils were obtained from 9 healthy cross‐bred ponies. The number of eosinophils used for each injection varied between 20 and 300 millions. The guinea‐pigs were exposed to a 0.6% histamine aerosol 1 to 8 hr later. The eosinophils of 5 ponies produced protection against the aerosol, the eosinophils of the other 4 ponies did not. Protection when produced did not last as long as 23 hr. The active principle in the watery extracts was stable, after freeze drying, for at least a few weeks.
EFFECT OF RESERPINE ON THE ACETYLCHOLINE CONTENT OF THE HEART, THE ILEUM AND THE HYPOTHALAMUS OF THE DOG
Authors: MALHOTRA C. L. , DAS P. K.
Published: July 2012

The effect of intravenous administration of reserpine in 10 dogs was studied on the acetylcholine content of the sino‐atrial node, the right auricle and the right ventricle of the heart, the ileum and the hypothalamus of dog. The general sedation, the bradycardia, and the purgative effects of reserpine were also noted. Tissues were removed for estimation of acetylcholine when bradycardia was maximal. Reserpine increased the acetylcholine content of all the tissues studied. The increase in the peripheral tissues was greater than in the hypothalamus. The bradycardia and the purgative effects of reserpine may be related to the increase of the acetylcholine content of the sino‐atrial node and the ileum.
TOXIC EFFECT OF CARBON TETRACHLORIDE ON THE LIVER CELL
Authors: ATERMAN K.
Published: July 2012

Rats and mice were given injections of carbon tetrachloride into the portal vein or into the spleen, and the localization of the resulting hepatocellular lesions was studied. In contrast to some statements in the literature, and confirming some older reports, damage was found to be limited to the periportal areas. A range of changes leading to cell necrosis was found, which was frequently associated with pronounced vasodilatation. These features were considered to be evidence in favour of a direct hepatotoxic effect of carbon tetrachloride, and are difficult to reconcile with the view, formulated again recently by some workers, that carbon tetrachloride acts indirectly on the liver cell by producing vasoconstriction.
EFFECT OF ALDOSTERONE AND CORTISOL ON LEPTAZOL‐INDUCED SEIZURES IN RATS
Authors: SELLER M. J. , SPECTOR R. G.
Published: July 2012

Leptazol B.P. (0.2 ml./kg) produced convulsions in 65% of normal adult rats with no fatalities. The same dose of leptazol in animals which had previously been given 0.125 mg/kg aldosterone resulted in fits in 70.2% with 7.7% deaths. Cortisol pretreatment (25 mg/kg) resulted in fits in 82.9%, and 12.2% of the animals died in convulsions. The incidence of convulsions in the animals treated with aldosterone and leptazol was not significantly increased above the animals treated with leptazol. The cortisol‐leptazol group did exhibit a significantly raised incidence of fits.
ADRENALINE, ANTI‐ADRENALINE DRUGS AND POTASSIUM MOVEMENTS IN RABBIT AURICLES
Authors: STAFFORD ANNE
Published: July 2012

Adrenaline (2 × 10−6m) or isoprenaline (7.5 × 10−8m) increased the rate of42K uptake and the potassium content of right (spontaneously beating) auricles, but had no effect on potassium movements in quiescent left auricles. Although faster beating induced by electrical stimulation increased the rate of42K uptake, the actions of adrenaline were also apparent in auricles which were electrically stimulated so that they beat at a constant rate. The increase in42K uptake produced by adrenaline accounted entirely for the increase in potassium content of the tissue. Adrenaline, in concentrations ranging from 2 × 10−6mto 2 × 10−4m, had no effect on42K loss from electrically stimulated auricles. The action of adrenaline on42K uptake was blocked by dichloroisoprenaline (4 × 10−6m) but not by phenoxybenzamine (1.6 × 10−6).
EFFECTS OF SINGLE AND REPEATED DOSES OF RESERPINE ON THE SECRETION OF ADRENOCORTICOTROPHIC HORMONE
Authors: MONTANARI R. , STOCKHAM M. A.
Published: July 2012

The effects of single and repeated doses of reserpine on the secretion of adreno‐corticotrophic hormone (ACTH) were studied in rats by determining changes in the adrenal and plasma concentrations of corticosterone, in the adrenal ascorbic acid levels, and in the adrenal gland weights. Treatment with doses of reserpine which induced sedation caused prolonged hypersecretion of ACTH. Such treatment did not impair the release of ACTH in response to a stressful stimulus as recorded by an increase in the plasma corticosterone even when there was no concomitant depletion in the adrenal ascorbic acid. This finding casts doubt on the value of the adrenal ascorbic acid determination as an index of ACTH secretion.
AN ESERINE‐LIKE ACTION OF CHLORAL HYDRATE
Authors: BROWN D. A.
Published: July 2012

The intra‐arterial injection of chloral hydrate potentiated the transmission of nerve impulses through the cat superior cervical ganglion, antagonized the ganglion‐blocking action of hexamethonium, and greatly enhanced the ganglion‐stimulant action of acetylcholine. Effects on the ganglion‐stimulant actions of carbachol, nicotine, tetramethylammonium and potassium chloride were slight or absent. Chloral hydrate itself usually had no direct stimulant action. The neuromuscular‐blocking action of tubocurarine on the isolated rat diaphragm preparation was completely and rapidly reversed by chloral hydrate. This reversal was prevented by previous treatment of the muscle with neostigmine. Chloral hydrate potentiated the actions of acetylcholine and nicotine on the isolated rabbit duodenum, and, in concentrations exceeding 1 mg/ml., produced a spasm which was abolished by hyoscine but not by mepyramine. It was concluded that these eserine‐like effects were manifestations of an anticholinesterase action of chloral hydrate. Neither chloralose nor trichlorethanol showed evidence of this property.
ASSAY OF OXYTOCIN BY RAT MAMMARY GLAND IN VITRO
Authors: RYDÉN G. , SJÖHOLM I.
Published: July 2012

A new method for quantitative assay of oxytocin using strips from rat mammary gland in vitro has been investigated. The method is very suitable for determination of small amounts of oxytocin. Doses down to 2 μ‐u. oxytocin have been estimated. The dose‐response curve is shown to be linear, and the precision of the method is good (λ =0.10 to 0.14). The effect of adrenaline, noradrenaline, acetylcholine, histamine and 5‐hydroxytryptamine on the rat mammary gland has also been tested.
INFLUENCE OF METALS ON THE ACTIVITY OF A BRADYKININ‐DESTROYING ENZYME KININASE
Authors: AARSEN P. N. , KEMP A.
Published: July 2012

Kininase prepared from guinea‐pig serum was inhibited by cysteine at pH 7.4 to 7.6. A similar effect was found with edetic acid. The enzyme blocked by edetic acid was reactivated immediately by addition of Mn++, Co++ and Zn++. These findings indicate that kininase is a metal‐activated enzyme.
POTENTIATION OF THE RESPONSE TO HISTAMINE BY PICOLYLAMINES
Authors: BLASCHKO H. , KURZEPA S.
Published: July 2012

The response of the isolated ileum of the guinea‐pig to histamine is potentiated in the presence of 2‐, 3‐ or 4‐picolylamine. These compounds have been found to inhibit the histaminase and/or “diamine oxidase” of pig kidney. The three corresponding picolylmethylamines did not potentiate the response of the ileum to histamine; they were without significant affinity for the pig kidney oxidase. It is suggested that the potentiating action of the three primary amines is due to their inhibitory action on histaminase. The responses of the ileum to acetylcholine and 5‐hydroxytryptamine were not potentiated.
ADRENERGIC NEURONE BLOCKADE AND OTHER ACUTE EFFECTS CAUSED BY N‐BENZYL‐N′N″‐DIMETHYLGUANIDINE* AND ITS ORTHO‐CHLORO DERIVATIVE
Authors: BOURA A. L. A. , GREEN A. F.
Published: July 2012

N‐Benzyl‐N′N′‐dimethylguanidine sulphate (BW 467C60) and its ortho‐chloro derivative (BW 392C60) had adrenergic neurone blocking and sympathomimetic effects resembling those of bretylium and guanethidine in cats, dogs and monkeys, but they were more potent in blocking adrenergic mechanisms in the cat. BW 467C60 was more active than its chloro derivative. Each compound inhibited release of noradrenaline during stimulation of the splenic nerve of cats, and increased smooth muscle responses to adrenaline and noradrenaline. Pressor responses to standard doses of tyramine were also increased except when large doses of BW 467C60 or BW 392C60 were given. The adrenergic neurone block by BW 467C60 was inhibited by dopamine, cocaine and amphetamine in situations in which these amines inhibit the effects of bretylium and guanethidine. In contrast to guanethidine, BW 467C60 and BW 392C60 did not lower the pressor amine content of the iris of cats 24 hr after administration of single doses of the compounds. BW 467C60 depressed the slope of curves relating the frequency of stimuli applied to the cervical sympathetic nerves and the resulting contraction of the nictitating membrane, but the effects of the lower rates of stimulation were preferentially inhibited. Large intravenous doses of BW 467C60 and BW 392C60 blocked autonomic cholinergic mechanisms and caused neuromuscular paralysis of voluntary muscle. These effects were brief, in contrast to the adrenergic neurone blockade. Both BW 467C60 and BW 392C60 were well absorbed from the alimentary tract. In contrast to guanethidine, BW 467C60 did not cause diarrhoea in guinea‐pigs.
AN ANALYSIS OF THE DIRECT AND INDIRECT ACTIONS OF DRUGS ON THE ISOLATED GUINEA‐PIG ILEUM
Authors: DAY MARGARET , VANE J. R.
Published: July 2012

The responses of the isolated guinea‐pig ileum to coaxial stimulation of its nerves, to histamine, acetylcholine, bradykinin, nicotine, tetramethylammonium, 1,1‐dimethyl‐4‐phenyl‐piperazinium iodide and 5‐hydroxytryptamine were studied, before and during anoxia, cooling, or exposure to hyoscine, phenoxybenzamine hydrochloride, morphine or hexamethonium. Dose ratios were used to determine the amount of block induced by these procedures. With the response to coaxial nerve stimulation as an indication of the excitability of the nervous tissue, it was found that anoxia or cooling abolished the response to single shocks. Under these conditions the response of the ileum to histamine, acetylcholine and bradykinin was hardly affected, indicating a direct action of these substances on the muscle fibres. The effects of nicotine, tetramethylammonium, dimethylphenylpiperazinium and 5‐hydroxytryptamine were reduced to various degrees, and we have concluded that their main actions are indirect, through stimulation of cholinergic nerve fibres. When these indirect actions were prevented, increasing the dose revealed a direct action, a larger increase in dose being required for 5‐hydroxytryptamine and dimethylphenylpiperazinium than for tetramethylammonium and nicotine. Exposure of the ileum to hyoscine and phenoxybenzamine showed that these direct actions of nicotine and tetramethylammonium were not only on acetylcholine receptors but also on receptors insensitive to hyoscine but sensitive to phenoxybenzamine. The main action of 5‐hydroxytryptamine was on nervous elements, yet treatment of the ileum with phenoxybenzamine gave a higher dose ratio for 5‐hydroxytryptamine than did treatment with morphine. The meaning of this result is discussed in relation to the general belief that receptors sensitive to morphine are in nervous tissue and receptors sensitive to phenoxybenzamine are in smooth muscle. We have concluded that morphine is only a partial antagonist of 5‐hydroxytryptamine receptors in nervous tissue and that phenoxybenzamine antagonizes more 5‐hydroxytryptamine receptors than those in smooth muscle.
PHARMACOLOGICAL RESPONSES OF THIAMINE‐DEFICIENT RAT TISSUES
Authors: BOULLIN D. J.
Published: July 2012

Rats were rendered deficient in thiamine by feeding a synthetic diet free of the vitamin. Responses of the isolated heart to acetylcholine, adrenaline, noradrenaline and isoprenaline, and of the phrenic nerve‐diaphragm preparation to tubocurarine, gallamine and eserine, were compared with responses of tissues obtained from litter‐mate rats pair‐fed an identical diet with the addition of 25 μg of thiamine hydrochloride per day. In thiamine‐deficient tissues eserine failed to produce sustained potentiation of the twitch response of the phrenic nerve‐diaphragm preparation to single supramaximal nerve stimuli. The perfused thiamine‐deficient heart was more sensitive to acetylcholine, adrenaline, noradrenaline and isoprenaline, which produced greater negative or lesser positive chronotropic and inotropic effects. There was no significant difference in the response of the phrenic nerve‐diaphragm preparation to tubocurarine and gallamine, or to eserine with faradic stimulation.
STUDIES ON THE REPETITIVE DISCHARGES EVOKED IN MOTOR NERVE AND SKELETAL MUSCLE AFTER INJECTION OF ANTICHOLINESTERASE DRUGS
Authors: BLABER L. C. , BOWMAN W. C.
Published: July 2012

Repetitive discharges recorded from the ventral root and from the gastrocnemius muscle in response to single motor nerve shocks applied close to the muscle after injection of edrophonium, neostigmine or ambenonium were studied in cats anaesthetized with chloralose. Two closely spaced volleys with an interval of 1 to 5 msec between them produced more repetitive firing than did a single shock. With longer intervals, the repetitive firing was not potentiated by the second volley. All frequencies of tetanic stimulation depressed the repetitive firing and, for successive stimuli to produce a degree of repetitive firing equivalent to the first, it was necessary to stimulate at frequencies below 2 shocks/sec. With stimulation frequencies higher than 100 shocks/sec, repetitive firing did not occur unless the duration of the tetanus was shorter than about 30 msec when slight repetition followed the last stimulus of the train. With stimulation frequencies of 100 down to 20 shocks/sec, repetitive firing was produced only by the first volley of the tetanus. Subsequent nerve action potentials of the tetanus occurring during the repetitive firing in the nerve following the first volley were partially extinguished by collision with the back discharge. This effect contributed to the waning tetanus, which is characteristic of treatment with an anticholinesterase, but the main depression of tetanic contractions appeared to be a consequence of depolarization block through accumulating acetylcholine. Tubocurarin and benzoquinonium reversed the initial “extinction” phase of the depressed tetani by abolishing the repetitive discharge in the nerve and in larger doses reversed the secondary depressant phase presumably by reducing the excessive end‐plate depolarization. The results are discussed in relation to the hypothesis that anticholinesterases may effect transmission by acting at three sites at the neuromuscular junction—on acetylcholinesterase, at the motor nerve ending and at the motor end‐plate—and that reaction at any one site may be augmented by the production of reverberating activity across the junction.
THE ACTION OF SUBSTANCES WHICH BLOCK SYMPATHETIC POSTGANGLIONIC NERVOUS TRANSMISSION
Authors: BURN J. H. , FROEDE H.
Published: July 2012

The substances which block sympathetic postganglionic transmission, xylocholine, bretylium and guanethidine, also block neuromuscular and sympathetic ganglionic transmission. To see if these last properties were related to the sympathetic blocking property, phenyltrimethylammonium, which blocks the neuromuscular junction (Riker, 1953), was used. It blocked the inhibition of the rabbit ileum produced by stimulating the periarterial nerves in the mesentery, though with higher concentrations the effect of stimulation was initially increased. The action was not modified by the presence of hyoscine. The blocking action was exerted on the response to stimulation of the highest frequency first, and on the response to stimulation of the lowest frequency last. This relation of block to stimulus frequency is similar to that at the neuromuscular junction when tubocurarine is used. Nine compounds have now been shown to block responses to sympathetic postganglionic stimulation, and seven of these are onium compounds. They are, however, mon‐onium compounds, and not bis‐onium compounds like hexamethonium and decamethonium, so that they can probably enter the postganglionic fibre, which bis‐onium compounds (having a charged group at each end of the molecule) may not be able to do. Since these mon‐onium compounds have some blocking action at neuromuscular junctions and at sympathetic ganglia, their block of postganglionic transmission may be essentially similar to that by hexamethonium at ganglia and to that by decamethonium at neuromuscular junctions. It is known that acetylcholine releases noradrenaline from sympathetic postganglionic terminations, and xylocholine and bretylium block this release in the vessels of the rabbit ear and in the rabbit isolated atria.
VASODEPRESSION INDUCED BY ACETYLCHOLINE IN THE ATROPINIZED DOG
Authors: GARDIER R. W. , JAMES E. A. , JOHNSON P. C. , RICHARDS A. B. , ROESCH R. P.
Published: July 2012

The pressor response to acetylcholine in the atropinized dog resulted from an increase in cardiac output. The pressor response was attributed solely to the release of adrenaline from the adrenal medulla. After giving compound P‐286 (N‐diethylamino‐ethyl‐N‐isopentyl‐N″N″‐di‐isopropylurea) to these dogs, acetylcholine lowered blood pressure, owing to a decrease in total peripheral resistance in the absence of an increase in cardiac output. P‐286 presumably blocked the liberation of adrenaline from the adrenal glands by acetylcholine. The blood vessels contributing to the fall in peripheral resistance were not in the intestines. The fall in blood pressure was not blocked by dichloroisoprenaline and it was still present in dogs treated with reserpine. It is suggested that the fall in blood pressure was due to stimulation of ganglion cells subserving vasodilatation.
THE MECHANISM OF THE EMETIC ACTION OF SODIUM SALICYLATE
Authors: BHARGAVA K. P. , CHANDRA OM , VERMA D. R.
Published: July 2012

In the dog, the emetic ED50 for sodium salicylate was 256 ± 113 mg/kg for the intravenous route with a mean latency of 10.4 ± 3.96 min, and for the oral route 228 ± 68 mg/kg with a mean latency of 18.2 ± 2.63 min. Values are means with standard errors. Ablation of the emetic chemoreceptor trigger‐zone gave complete protection against the emetic action of 300 mg of sodium salicylate intravenously but only partial protection against the emetic action of the same dose of sodium salicylate orally. Either the intravenous salicylate acted on the trigger‐zone or ablation of the trigger‐zone interfered with afferent nerves from peripheral receptors responding to intravenous salicylate and which were different from the receptors responding to oral salicylate. After supradiaphragmatic vagotomy, there was equal protection against intravenous and oral salicylate. Two explanations can be advanced. First, the receptors responding to intravenous and those responding to oral salicylate have a common path in the vagus nerves; or second, afferent fibres in the vagus nerve normally maintain the vomiting centre in a reactive state. When these fibres are cut any other afferent fibres become less effective in evoking vomiting. Spinal transection gave partial and spinal transection with vagotomy gave complete protection. It is concluded that further work is necessary to decide which of the two explanations obtained.
EFFECTS OF ANTI‐RHEUMATIC COMPOUNDS AND PYRIDINE DERIVATIVES ON THE CUTANEOUS RESPONSE TO THURFYL NICOTINATE IN THE GUINEA‐PIG
Authors: HAINING C. G.
Published: July 2012

The effects of certain anti‐rheumatic drugs and compounds related to nicotinic acid on the cutaneous response to locally applied thurfyl nicotinate in guinea‐pigs were investigated. Sodium salicylate, aspirin or phenylbutazone administered orally each reduced the response to thurfyl nicotinate at about half the dose needed for equivalent protection against the cutaneous effects of exposure to ultra‐violet light. Nicotinic acid or thurfyl nicotinate given orally flushed the skin and reduced the intensity of the local reaction to thurfyl nicotinate without affecting the response to ultra‐violet light. Nicotinamide, isonicotinic acid, picolinic acid and quinolinic acid were less effective in producing flushes and in reducing the effect of locally applied thurfyl nicotinate. The flush induced in guinea‐pigs by oral nicotinic acid was reduced by the previous administration of phenylbutazone. Possible mechanisms for these effects are discussed.
THE MODE OF ACTION OF NEOSTIGMINE AND PHYSOSTIGMINE ON THE GUINEA‐PIG TRACHEALIS MUSCLE
Authors: CARLYLE R. F.
Published: July 2012

Neostigmine (2.2 μg/ml.) or physostigmine (3.3 μg/ml.) contracted guinea‐pig isolated tracheal chains. The anticholinesterase diisopropylphosphodiamidic fluoride (mipafox) itself caused no contractile response even in concentrations of 100 μg/ml., yet neostigmine or physostigmine still caused contractions after treatment with mipafox. The responses were abolished by hyoscine or atropine. Local anaesthetics, cooling, ionic changes and hemicholinium, all known to inhibit the release of acetylcholine from nerve endings, abolished or much reduced the responses. It seems that the contractile response to physostigmine or neostigmine does not depend on their anticholinesterase activity, but on their ability to release acetylcholine from postganglionic parasympathetic nerve endings.
CARDIAC AND VASCULAR EFFECTS OF SYMPATHOMIMETIC DRUGS AFTER ADMINISTRATION OF TRIIODOTHYRONINE AND RESERPINE
Authors: BENFEY B. G. , VARMA D. R.
Published: July 2012

In spinal cats treated with tri‐iodothyronine, the effects of sympathomimetic drugs on cardiac contraction were diminished. Ouabain failed to restore the effects on the contractile force of the heart. The effects of sympathomimetic drugs on the force of contraction of papillary muscle were not reduced by tri‐iodothyronine, but the threshold for induction of automaticity was lowered. There was no evidence that in cats treated with reserpine the sensitivity of peripheral vessels to sympathomimetic agents is decreased and that blood pressure changes are merely secondary to changes in cardiac contraction.
A STUDY OF GRANULES AND OTHER CHANGES IN PHASE‐CONTRAST APPEARANCE PRODUCED BY CHEMOTHERAPEUTIC AGENTS IN TRYPANOSOMES
Authors: ORMEROD W. E. , SHAW J. J.
Published: July 2012

The morphological changes produced by four series of organic trypanocidal drugs have been studied by quantitative and by qualitative methods using phase‐contrast and fluorescence microscopy. Basic drugs were absorbed rapidly into the region of the kinetoplast; acidic drugs did not affect this region. Faint granules, which were present in some trypanosomes before the administration of drugs, absorbed the drugs and increased in contrast relative to the cytoplasm. Hydroxystilbamidine, quina‐pyramine, related compounds, and possibly also suramin produced additional granules which did not contain drug. These additional granules are similar to the granules (volutin granules) which occur in trypanosome infections (not treated with drugs) when trypanosomes are about to be cleared from the blood. Homidium did not produce additional granules.
THE SITE OF THE 5‐HYDROXYTRYPTAMINE RECEPTOR ON THE INTRAMURAL NERVOUS PLEXUS OF THE GUINEA‐PIG ISOLATED ILEUM
Authors: BROWNLEE G. , JOHNSON E. S.
Published: July 2012

Dose/response measurements were made on the guinea‐pig isolated ileum with six agonists, acetylcholine, 5‐hydroxytryptamine, nicotine, dimethylphenylpiperazinium, choline phenyl ether and histamine. The dose effects were repeated in the presence of each of twelve antagonists and one anticholinesterase. Acetylcholine and histamine were chosen because of their direct mode of action on smooth muscle, nicotine, dimethylphenylpiperazinium and choline phenyl ether were used as examples of drugs that act at the ganglionic acetylcholine receptor. 5‐Hydroxytryptamine was the drug investigated. Hyoscine blocked the contractions caused by acetylcholine, 5‐hydroxytryptamine and the ganglion‐stimulants but left the responses to histamine unchanged. The anticholinesterase N,N'‐diisopropylphosphorodiamidic fluoride (mipafox) potentiated all the agonists except histamine. The strength of potentiation decreased in the order 5‐hydroxytryptamine, nicotine, dimethylphenylpiperazinium and choline phenyl ether, and acetylcholine. The local anaesthetic procaine inhibited to the same extent contractions elicited by 5‐hydroxytryptamine, nicotine, dimethyl‐phenylpiperazinium and choline phenyl ether. These results showed that 5‐hydroxytryptamine, like nicotine, choline phenyl ether and dimethylphenylpiperazinium, mediated its response through the nervous plexus. Of those tested 5‐hydroxytryptamine was the only specific antagonist to 5‐hydroxytryptamine; lysergic acid derivatives produced spasm and prolonged changes in tone; phenoxybenzamine caused non‐specific block. The diverse modes of action of a number of ganglion‐blocking agents were selectively used. Thus hexamethonium, pentolinium, and nicotine in its competitive phase, blocked contractions due to nicotine, dimethylphenylpiperazinium and choline phenyl ether and left those due to 5‐hydroxytryptamine, acetylcholine and histamine unchanged. The depolarizing ganglion‐blocking agents, dimethylphenylpiperazinium and nicotine, inhibited the responses to all the indirectly acting drugs. Furthermore, mecamylamine, a drug with a less well‐defined mode of action, partially inhibited contractions due to 5‐hydroxytryptamine in a concentration that blocked those due to nicotine, dimethylphenylpiperazinium and choline phenyl ether. Pempidine, known to act like mecamylamine, did not antagonize 5‐hydroxytryptamine. It is concluded that 5‐hydroxytryptamine activates specific receptors sited at the intramural parasympathetic ganglion cells.
MECHANISM OF ATRIAL FLUTTER AND FIBRILLATION INDUCED BY ACONITINE IN THE DOG, WITH OBSERVATIONS ON THE ROLE OF CHOLINERGIC FACTORS
Authors: SHARMA P. L.
Published: July 2012

The topical application of aconitine nitrate to the right atrial appendage in the “intact” anaesthetized dog produced atrial flutter. Premature systoles with fixed coupling preceded the development of flutter. In early stages of the arrhythmia, atrial rate was irregularly irregular. Also, the form of flutter beats was similar to that of preceding premature systoles. The fibrillatory activity of acetylcholine described by earlier workers has been confirmed. Transient atrial dissociation was seen after intravenous injection or topical application of acetylcholine. The occurrence of fibrillation in the left atrium after focal application of acetylcholine has been demonstrated, while the right atrial appendage containing the ectopic focus induced by aconitine continued to flutter. Aconitine produced slow‐rate flutter in dogs treated with atropine or hemicholinium; this flutter was easily distinguishable from the sinus tachycardia produced by these drugs, by recording the electrocardiogram from a direct atrial lead from the area treated with aconitine. but not from limb lead II. The importance of these findings in the interpretation of the mechanism of atrial flutter and fibrillation is discussed.
THE β‐ADRENERGIC BLOCKING AND PRESSOR ACTIONS OF ISOPRENALINE IN THE CAT
Authors: BUTTERWORTH K. R.
Published: July 2012

In the anaesthetized cat a single, large, intravenous dose of (–)‐isoprenaline reversibly blocked the depressor properties of isoprenaline. Further large doses then caused monophasic rises in blood pressure, which were similar in rate of onset and duration to those produced by adrenaline and noradrenaline. This pressor effect was not due to an increase in cardiac output, but the main cause was vasoconstriction in skeletal muscle. The responses to isoprenaline, adrenaline and noradrenaline were compared, both before and after the blocking dose of isoprenaline. Isoprenaline prevented or antagonized the potentiation of the pressor effects of adrenaline and noradrenaline by cocaine. The pressor effect was blocked but not reversed by ergotamine and tolazine, which block sympathetic α‐receptors. It is suggested that isoprenaline in large doses has two actions on the vascular system of the cat: a blockade of the sympathetic β‐receptors and an excitation of α‐receptors.