bluuebunny/crossref_metadata_2025 huggingface dataset:
THE EFFECT OF RESERPINE ON THE PRESSOR RESPONSE TO INJECTION OF 2‐HALOGENOETHYLAMINE
Authors: GRAHAM J. D. P.
Published: July 2012

Dibenamine‐like compounds sometimes caused an increase in blood pressure when injected intravenously in mammals. This response varied with species, with the preparation, and with the structure of the compound. The response became smaller after repeated injections. In spinal atropinized rats injected with hexamethonium 5 mg/kg this pressor effect produced by injection of the adrenaline antagonist, compound AT3 [ethylfluoren‐9‐yl(2‐iodoethyl)amine hydriodide], was reduced by prior treatment for five days with 1 mg/kg reserpine. Acute adrenalectomy also reduced this effect of the adrenaline antagonist; reserpine plus adrenalectomy abolished it. Subsequent injection of adrenaline and noradrenaline restored it.
THE ACTIONS OF AMYLOBARBITONE SODIUM, BUTOBARBITONE AND QUINALBARBITONE SODIUM UPON INSOMNIA AND NOCTURNAL RESTLESSNESS COMPARED IN PSYCHIATRIC PATIENTS
Authors: HINTON J. M.
Published: July 2012

Amylobarbitone sodium, butobarbitone, quinalbarbitone sodium, and a placebo were compared in a controlled, double‐blind trial in psychiatric patients with insomnia. An apparatus recording movement in bed is described, with sleep assessments by night nurses and patients. All three barbiturates significantly reduced movement and gave significantly longer, less broken and sounder sleep, without increased incidence of “hang‐over.” There was no follow‐on effect from night to night. With effective doses there was no significant difference between these barbiturates in onset and duration of hypnotic action, although usually accepted as either short or intermediate acting.
EFFECT OF ANTIBIOTICS ON THE 5‐HYDROXYTRYPTAMINE CONTENT OF THE SMALL INTESTINE AND OTHER ORGANS IN RATS AND MICE
Authors: SULLIVAN T. J.
Published: July 2012

Rats and mice were given antibiotics orally and by subcutaneous injection and the effects on tissue levels of 5‐hydroxytryptamine and intestinal bacteria were studied. In mice it was found that antibiotics which caused a large reduction in the bacterial flora of the intestine when given orally also caused a significant increase in intestinal 5‐hydroxytryptamine. In rats, neomycin caused a reduction in the urinary excretion of 5‐hydroxyindoleacetic acid. In both rats and mice, many antibiotics caused a significant reduction in the weight of the spleen.
ANTIHISTAMINASE ACTIVITY OF SERPENTINE
Authors: SACHDEV K. S. , AIMAN RANITA , RAJAPURKAR M. V.
Published: July 2012

Serpentine, an alkaloid of Rauwolfia serpentina, specifically potentiates histamine responses of guinea‐pig ileum, uterus, and tracheal chain. It also inhibits histaminase in vitro. Its antihistaminase activity is equivalent to that of aminoguanidine.
SOME INHIBITORS OF HISTAMINE‐INDUCED AND FORMALDEHYDE‐INDUCED INFLAMMATION IN MICE
Authors: NORTHOVER B. J. , SUBRAMANIAN G.
Published: July 2012

The swelling and capillary hyperpermeability of the mouse foot in response to an injection of formaldehyde, and the increased capillary permeability to an intradermal injection of histamine, have been investigated. Cortisone, mepyramine and sodium salicylate were effective in reducing histamine‐induced inflammation, sodium salicylate being less active in the adrenalectomized animal. In formaldehyde‐induced inflammation, however, cortisone was ineffective whereas sodium salicylate was effective in the intact mouse, but not in the adrenalectomized animal. Certain aryloxypropionates and anti‐esterases were also active in reducing the severity of the formaldehyde‐induced inflammation.
SALICYLATE AND LIVER GLUTATHIONE
Authors: SPROULL D. H.
Published: July 2012

The effects of sodium salicylate, benzoate, gentisate, m‐ and p‐hydroxybenzoates, antipyrine, and 2:4‐dinitrophenol on the reduced glutathione concentration of rat liver were determined. An increase in concentration in the male, but not in the female, rats was found after salicylate, benzoate and gentisate; after antipyrine, a comparable increase occurred in the females only. There is a relation, in these compounds, between capacity to increase the concentration of reduced glutathione in the rat liver in one sex and therapeutic activity in rheumatic fever.
METABOLISM OF [14C]‐HISTAMINE IN HEART‐LUNG‐LIVER PREPARATIONS OF CATS
Authors: LILJA B. , LINDELL S.‐E.
Published: July 2012

The metabolism of injected [14C]‐histamine was studied in heart‐lung‐liver preparations and heart‐lung preparations from cats. When the liver was included in the circulation the injected histamine was rapidly eliminated from the blood, some of its metabolites appearing in the blood within 2 min after the injection. More than 70% of the injected histamine was metabolized to 1‐methylimidazol‐4‐ylacetic acid. In the heart‐lung preparations [14C]‐histamine disappeared much more slowly from the blood and the major metabolite was 4‐(2‐aminoethyl)‐1‐methylimidazole (methylhistamine). Less than 4% of the injected 14C was recovered in the form of imidazol‐4(or 5)‐ylacetic acid. In none of the experiments was there any measurable formation of acetylhistamine.
POTENTIATION OF SUBSTANCE P BY LYSERGIC ACID DIETHYLAMIDE IN VIVO
Authors: KRIVOY W. A.
Published: July 2012

In doses of 10 μg/kg or more, lysergic acid diethylamide enhanced the fourth potential (DR IV) of the dorsal root potential complex in the cat. Smaller doses of lysergic acid diethylamide did not in themselves alter the DR IV, but revealed an enhancement of the potential by substance P, which by itself had no effect. 2‐Bromolysergic acid diethylamide had no action on the dorsal root potentials, but prevented the actions of lysergic acid diethylamide.
TACHYPHYLAXIS TO THE ANTI‐TETANUS ACTIVITY OF SOME PHENOTHIAZINE COMPOUNDS
Authors: LAURENCE D. R. , WEBSTER R. A.
Published: July 2012

Although chlorpromazine and acepromazine were the most potent suppressants of local tetanus induced in rabbits by intramuscular injection of the toxin of CI. tetani, repeated injections lost their effect (tachyphylaxis) and sometimes even increased muscle activity, as did single large injections of either of the two drugs. As neither tachyphylaxis nor stimulation occurred in spinal animals, these effects might arise from an action in the brain‐stem reticular formation on which chlorpromazine has been shown to have both inhibitory and excitatory effects. The possible cause of the tachyphylaxis is discussed. Evidence is advanced to support the view that tachyphylaxis can occur when chlorpromazine is used in the treatment of tetanus in man. Methotrimeprazine was more potent than chlorpromazine, but less prone to induce tachyphylaxis. These qualities rendered it more desirable for clinical use than the other two compounds.
SOME OBSERVATIONS ON PECKING IN PIGEONS
Authors: DESHPANDE V. R. , SHARMA M. L. , KHERDIKAR P. R. , GREWAL R. S.
Published: July 2012

An attempt was made to analyse the pecking behaviour in pigeons induced by apomorphine. The pecking was completely suppressed by tranquillizers, barbiturates and cortisone. It was intensified by histamine, nicotine, lobeline, testosterone, progesterone and sodium taurocholate. None of the drugs tested could induce in pigeons pecking typical of apomorphine. Apomorphine induced pecking in other birds too. It was concluded that the pecking phenomenon after apomorphine is similar to the natural feeding movements performed by pigeons while eating grains and possibly it is the function of a specialized area in the limbic system of the brain which is stimulated by apomorphine.
THE EFFECT OF ATROPINE, PROPANTHELINE AND POLDINE ON THE VAGALLY STIMULATED GASTRIC MOTILITY AND THE HISTAMINE‐STIMULATED ACID GASTRIC SECRETION IN THE RAT
Authors: AARSEN P. N. , VAN NOORDWIJK J.
Published: July 2012

Histamine‐induced acid gastric secretion in the anaesthetized rat was not diminished by poldine in a dose which reduced vagally stimulated gastric contractions by approximately 75%. A dose of atropine, twice as large as the dose which reduced gastric contractions by 75%, had no apparent effect on the histamine‐stimulated acid gastric secretion up to 2 hr after the injection. Only when more than 40 times as much atropine was injected did a slight inhibition of the acid secretion occur in 80 to 120 min. Propantheline, in a dose which inhibited gastric contractions by approximately 75%, slightly diminished acid secretion in 40 to 80 min. This effect was not increased by a further dose of propantheline. It was concluded that, in so far as any inhibition of acid gastric secretion had occurred, this could not be interpreted as an anti‐muscarine or a direct toxic effect, but rather as an indirect effect possibly due to interference with the blood flow through the stomach wall.
EFFECTS OF DRUGS ON PARTIALLY AND COMPLETELY DENERVATED SKELETAL MUSCLE OF THE FROG
Authors: FRANK G. B.
Published: July 2012

The sensitivity of completely denervated and the innervated end‐plate regions of partially denervated frog's sartorius muscles to stimulation by drugs has been investigated. The drugs were tested on muscles isolated 12 to 39 days following denervation. On the basis of the results obtained most of the drugs could be put into one of two main groups. The first group included choline, tetramethylammonium, carbachol and decamethonium; these drugs readily stimulated non‐denervated muscles, and chronic denervation, either partial or complete, greatly increased the sensitivity of the muscles. The second group included pilocarpine and carbamate of (2‐hydroxypropyl) trimethyl ammonium chloride (Bethanechol, U.S.P.). The muscles were relatively insensitive to stimulation by these two drugs. They could stimulate the muscles if applied in high enough concentrations, but the responses thus obtained could not be distinguished from responses produced by similar concentrations of sucrose and chronic denervation did not increase the sensitivity of the muscles to stimulation by these two drugs. Methacholine, like the drugs in the second group, was unable to stimulate the muscles in low concentrations, but chronic denervation rendered the muscles sensitive to stimulation by this drug. Tetraethylammonium presented a completely different pattern of activity which was consistent with a hypothesis that in low doses this drug stimulates skeletal muscle by causing a release of acetylcholine from nerve endings in the muscle.
ACTION OF BRETYLIUM ON THE ISOLATED GUINEA‐PIG ILEUM
Authors: KOSTERLITZ H. W. , LEES G. M.
Published: July 2012

Bretylium inhibits the contractions of the longitudinal muscle caused by histamine and, to a lesser extent, those by acetylcholine, carbachol and nicotine. It is a very weak antagonist of 5‐hydroxytryptamine and in concentrations of up to 190 μg/ml. does not inhibit the actions of bradykinin and substance P on the longitudinal muscle. The inhibitory effect of bretylium on the emptying phase of the peristaltic reflex is similar to that of ganglion blocking agents, while the much less pronounced effect on the contraction of the longitudinal muscle during the preparatory phase is assumed to be due to a weak atropine‐like action.
PERIPHERAL ACTIONS OF HEXAMETHONIUM IN RELATION TO THE DECREASING EFFECTS OF REPEATED DOSES ON THE BLOOD PRESSURE OF ANAESTHETIZED RATS
Authors: BLACKMAN J. G. , LAVERTY R.
Published: July 2012

When hexamethonium was given intravenously to anaesthetized rats, the depressor response produced by successive doses became less. This effect was not related to the duration of anaesthesia and the possible recovery of cardiovascular reflex activity. When the rat's own blood was perfused at constant rate through one hind limb, successive doses of hexamethonium reduced the hind‐limb perfusion pressure to the same extent each time, but their effect on the blood pressure of the remainder of the animal became less. When the hind limb was perfused at constant rate with blood from a separate donor rat, hexamethonium in the donor blood produced a very small increase in the vasoconstrictor response to noradrenaline in the innervated hind limb but not in the denervated hind limb.
ASSAY OF SUBSTANCE P ON THE FOWL RECTAL CAECUM
Authors: CLEUGH J. , GADDUM J. H. , HOLTON P. , LEACH E.
Published: July 2012

The optimum conditions for the assay of substance P on fowl rectal caecum have been studied. Effective concentrations vary from 0.01 to 0.5 u./ml.; it is remarkably insensitive to other polypeptides, such as bradykinin. The test can be made more specific by using a bath fluid containing antagonists for known interfering substances. A suitable antagonist for acetylcholine is atropine or hyoscine, for 5‐hydroxytryptamine, methysergide and for catecholamines, ephedrine. The effects of histamine and adenosine compounds can be abolished by specific tachyphylaxis, in which the bath fluid contains an excess of the active substance itself. The assay is reasonably accurate. Woolf's index of precision (L) was estimated as 15.5 with a range (9) of 9.2 to 29.4. Simplified methods of calculating L, and the fiducial range, are described.
STUDIES ON THE MODE OF ACTION OF METHYRIDINE
Authors: BROOME A. W. J.
Published: July 2012

Methyridine [2‐(β‐methoxyethyl)pyridine] reached the blood and all regions of the alimentary canal following oral or subcutaneous administration of therapeutic doses of the drug. Concentrations in the lower gut were highest following subcutaneous administration, and there was a close association between blood and intestinal levels suggesting that the drug is excreted into the alimentary canal along its whole length. In vitro experiments with intact nematodes (Ostertagia spp. from sheep; Nematospiroides dubius and Heterakis spumosa from mice; and Nippostrongylus muris from rats) and with preparations of Ascaris sp. have demonstrated that methyridine passes through the cuticle and exerts an “irreversible” paralysing effect on the worms. This action is obtained within 1 hr at concentrations similar to peak levels shown to be present in the alimentary canal following the administration of therapeutic doses. Concentrations of the drug were found to be higher in the abomasum than in the intestine of sheep and yet the anthelmintic activity of methyridine is greatest against intestinal nematodes. No significant differences in the resistance of various nematode species to the drug were demonstrated, but the amount of methyridine entering ascarids was significantly greater at pH 8 than at pH 5 or 3. In addition, the in vitro anthelmintic activity of the compound was greatest in alkaline solutions, which probably accounts for the differences in anthelmintic activity noted in various parts of the alimentary canal. The paralysing effect of methyridine on nematodes is probably due to a neuromuscular block of the decamethonium type, and this can also be produced in the host by over‐dosage. It is suggested that nematode tissues are more sensitive to this action than vertebrate tissues.
5‐HYDROXYTRYPTAMINE AND TRANSMISSION IN SYMPATHETIC GANGLIA
Authors: HERTZLER E. C.
Published: July 2012

Rat stellate ganglia were isolated and maintained in a moist chamber in which they were intermittently immersed in physiological saline containing low concentrations of the compound under investigation. 5‐Hydroxytryptamine (serotonin) in concentrations as low as 1.3 × 10−6 m reduced reversibly the threshold and increased the amplitude of responses to preganglionic stimulation. Certain antagonists of 5‐hydroxytryptamine depressed reversibly the postsynaptic responses. Experiments in vivo supported this finding. It is suggested that 5‐hydroxytryptamine facilitates transmission in the sympathetic ganglia of rats.
ASSAY OF SUBSTANCE P ON GOLDFISH INTESTINE IN A MICROBATH
Authors: GADDUM J. H. , SZERB J. C.
Published: July 2012

A technique is described for testing the effects of drugs on the intestine of goldfish in a microbath (0.05 ml.). This preparation may be used for the assay of substance P, which causes contractions of the muscle in doses as small as 1 m‐u. Other substances in tissue extracts also act on this muscle, but the effects of most of these can be abolished by antagonists. Some tissues, however, contain an unknown substance which causes powerful contractions of the muscle and interferes with the assay of substance P. An attempt to demonstrate the release of substance P in the central nervous system was unsuccessful.
DIURESIS IN RATS: EFFECTS OF SYMPATHOMIMETIC AND SYMPATHETIC BLOCKING AGENTS
Authors: GREEN A. F. , SIM M. F.
Published: July 2012

Dopamine and tyramine possess diuretic properties resembling but weaker than those of noradrenaline in the rat. These three amines produce a relatively smaller loss of sodium than does adrenaline. Bretylium shows a diuretic action which is apparently associated with its sympathomimetic properties and which is antagonized by phenoxybenzamine. However, bretylium causes a relatively greater loss of potassium and chloride than do the sympathomimetic amines. A slight antidiuretic action is shown by bretylium after its diuretic effect has subsided and a similar effect is produced by BW 172C58, which has relatively weak sympathomimetic properties. In contrast to these adrenergic neurone blocking agents, phenoxybenzamine and a ganglion blocking agent (pentacynium) show powerful antidiuretic effects. These observations are consistent with the view that the adrenal medulla has an important role in facilitating water diuresis in rats.
ACTION OF CHLOROTHIAZIDE ON THE DISTRIBUTION, EXCRETION AND HYPOTENSIVE EFFECT OF PEMPIDINE IN MAN
Authors: DOLLERY C. T. , EMSLIE‐SMITH D. , MUGGLETON D. F.
Published: July 2012

When chlorothiazide is given to hypertensive patients who are receiving pempidine a rise in plasma pempidine concentration occurs and this is proportionately greater than the additional fall in blood pressure. After pempidine has been added to human whole blood in vitro or in vivo the ratio of the pempidine concentration in the red cells to that in the plasma falls in the course of 1 hr from an initial value greater than 2 to about 1.2. If chlorothiazide is present also, however, the ratio remains constant at 0.7. Changes in the plasma pempidine concentration in vivo probably result from the binding of pempidine to plasma protein in the presence of chlorothiazide. This has been observed in vitro by a dialysis technique.
CENTRALLY ACTING MUSCLE RELAXANTS IN TETANUS
Authors: WEBSTER R. A.
Published: July 2012

The anti‐tetanus activity of a number of phenothiazine derivatives and other centrally acting muscle relaxants, such as mephenesin, dicyclopropyl ketoxime, 2‐amino‐6‐methylbenzothiazole and meprobamate, has been determined in rabbits with experimental local tetanus. Structure‐activity relationships were obtained for the phenothiazine derivatives and their anti‐tetanus activity correlated with other central and peripheral properties. Both dicyclopropyl ketoxime and 2‐amino‐6‐methyl‐benzothiazole were twice as active as mephenesin. Meprobamate does not appear to be primarily a muscle relaxant of the mephenesin type.
A COMPARATIVE STUDY OF STAPHYLOCOCCUS HAEMOLYSINS AND COLISAN
Authors: BERGMANN F. , LEON S. , CHAIMOVITZ M. , BENZAKEIN F.
Published: July 2012

Staphylococcus β‐haemolysin exhibits the same broad spectrum of antagonistic activity against smooth muscle stimulants as described recently for Colisan. The antispasmodic effect develops slowly and can be removed only by repeated washing. The pattern of haemolytic activities of Colisan is characteristically different from that of β‐haemolysin, but resembles closely α‐toxin. Both staphylococcus toxins can destroy paramecium and entamoeba, but the ratio of the titres at which they kill paramecium and entamoeba respectively (P:A value) is different. The P:A value of β‐haemolysin is similar to that of Colisan.
INTERACTIONS OF SYMPATHOMIMETIC DRUGS AND THEIR ANTAGONISTS ON THE ISOLATED ATRIUM
Authors: BENFEY B. G. , GREEFF K.
Published: July 2012

In the isolated guinea‐pig atrium, phenoxybenzamine and other antagonists of sympathomimetic drugs and the adrenergic nerve blocking agent guanethidine inhibited the action of butyrylcholine and tyramine and potentiated the action of noradrenaline. Also in the isolated guinea‐pig atrium, phenoxybenzamine and cocaine abolished the parasympathetic, and potentiated the sympathetic, effects of vagus stimulation.
ANTIGENIC PROPERTIES OF PURIFIED FRACTIONS FROM ASCARIS LUMBRICOIDES VAR. SUUM ON NATURALLY SENSITIZED GUINEA‐PIG
Authors: BERALDO W. T. , DA SILVA W. DIAS , PUDLES J.
Published: July 2012

Purified extract of Ascaris injected intravenously into guinea‐pigs produced a reaction very similar to the anaphylactic reaction. As shown by the ratio of deaths to survivals the toxic fraction contained in Ascaris extract was purified 3 to 4 times. After intravenous injection animals presented both anaphylaxis‐like shock and mast cell damage similar to that observed in anaphylaxis. Perfusion of the lungs with Ascaris fractions released histamine. Isolated guinea‐pig ileum when in contact with Ascaris fractions showed a response followed by desensitization. Heating the ileum to 45° C or previous desensitization to anaphylatoxin excluded the participation of the latter in this contraction. In vitro, sensitization from one guinea‐pig could be transferred to another, using spleen extract or a 50% ammonium sulphate precipitate obtained from the spleen extract. On the basis of these results it is concluded that guinea‐pigs are naturally sensitized to antigen or antigens present in Ascaris lumbricoides.
EFFECT OF RESERPINE ON GROWTH AND SEXUAL DEVELOPMENT OF CHICKENS
Authors: HAGEN P. , WALLACE A. C.
Published: July 2012

One‐month‐old male chickens were given injections of 1 mg, 2 mg and 4 mg/kg of reserpine. The injections were repeated at weekly intervals for three months. The chickens receiving reserpine grew at half the rate of untreated control chickens and failed to grow combs. At 4 months of age the testes of reserpine‐treated chickens were only about one‐tenth the weight of the testes of the control chickens and histologically they showed extreme hypoplasia of the seminiferous tubules. Two large doses of reserpine one month apart could cause atrophy of the testes of adult roosters.
PHARMACOLOGICAL STUDY AND FRACTIONATION OF PASPALUM SCROBICULATUM EXTRACT
Authors: BHIDE N. K.
Published: July 2012

The dried ethanol extract of the husk of the grain of Paspalum scrobiculatum produced tranquillization and tremors in various species of animals. It potentiated the effect of hexobarbitone in mice, produced hypothermia in mice and rats and enhanced leptazol toxicity in rats. Amphetamine group‐toxicity in mice increased after injecting the extract or an emulsion containing a similar quantity of olive oil. Vomiting in pigeons and decrease of morphine rage in cats were noted. Diminution of carotid occlusion reflex and hypotension were observed in anaesthetized dogs. Tremors and sleep were experienced by a human volunteer after taking the extract orally. Stability of the extract under different conditions was studied in dogs. Fractions of the extract, resolved by solvent separation and column chromatography, were tested in dogs for tranquillization and tremors.
EFFECTS OF ORGANOPHOSPHOROUS COMPOUNDS, OXIMES AND ATROPINE INJECTED INTO THE THIRD VENTRICLE OF UNANAESTHETIZED DOGS
Authors: EDERY H.
Published: July 2012

The effects of four organophosphorous compounds, three oximes and atropine sulphate, injected through an indwelling cannula into the third ventricle of unanaesthetized dogs were examined. The effects of 200 μg of dyflos were involuntary micturition, defaecation, akinesia of hind limbs and pronounced disturbances of awareness; those of 100 μg of ethyl pyrophosphate were tremor, restlessness and signs of fear; 500 μg to 5 mg of dyflos and 250 μg to 500 μg of ethyl pyrophosphate caused vomiting, salivation, twitches of facial muscles and recurrent epileptiform seizures. The injection of 40 to 80 mg of dimefox and of 50 mg of schradan elicited involuntary micturition, vomiting, salivation and defaecation. These effects occur probably after these substances have passed into the blood stream and have beep converted in the liver to potent anticholinesterases. This view is supported by the finding of reduced blood cholinesterase activity. At a dose level of 12.5 mg, 1,1′‐trimethylenebis(4‐hydroxyiminomethylpyridinium bromide) produced strong convulsions. At this dose level pralidoxime iodide and diacetyl monoxime produced no observable effects. Atropine sulphate in a dose of 1 mg caused disturbances in consciousness and behaviour followed by convulsions. Intraventricular atropine and to a minor extent intraventricular oximes were able to antagonize the effects of intraventricular ethyl pyrophosphate. Pralidoxime iodide exerted a strong antagonistic effect also on intravenous injection.
EFFECT OF DRUGS ON THE NORADRENALINE CONTENT OF BRAIN AND PERIPHERAL TISSUES AND ITS SIGNIFICANCE
Authors: SANAN SAROJ , VOGT MARTHE
Published: July 2012

Large single doses of methoserpidine (12 mg/kg) given to rabbits lowered the noradrenaline content of sympathetic ganglia but not that of brain; no sedation was observed. Cats responded to doses ranging from 12 to 0.5 mg/kg with loss of noradrenaline from ganglia as well as from brain, and were sedated by the drug. The effect in man resembles that in the rabbit. Only within the group of reserpine‐like drugs do sedation and loss in hypothalamic noradrenaline run parallel. These effects are therefore not causally related. Guanethidine lowers the noradrenaline content of sympathetic ganglia (cats and rabbits), but this effect does not explain the blocking action of the drug on the adrenergic nerve. Effects on the noradrenaline of the brain are variable and may be caused reflexly rather than by direct central action of guanethidine. Repeated intravenous injections of dimethylphenylpiperazinium iodide for a period of 4 hr did not produce any significant change in the noradrenaline content of ganglia or brain of rabbits. In contrast, dexamphetamine (20 mg/kg) produced a small but significant mean fall in noradrenaline content of the superior cervical ganglia and in that of the brain, but the effects were not seen in every rabbit. Prolonged administration of the mono‐amine oxidase inhibitors pheniprazine and phenylhydrazinobutane raised the noradrenaline content of the brain of rabbits but not that of cats, whereas it raised the noradrenaline of the ganglia of cats but not (or rarely) that of rabbits. The question of correlation between a rise in the noradrenaline content of the brain and certain clinical signs is discussed. Finally, a comparison is made in rabbits between the changes produced by drugs in the noradrenaline content of the heart and of the superior cervical ganglion. The changes run parallel and are only occasionally more pronounced in the heart.
AMOEBICIDAL ACTIVITY OF DICHLORO‐N‐2‐HYDROXY‐ETHYL‐N‐p‐METHYLSULPHONYLBENZYLACETAMIDE AND SOME RELATED COMPOUNDS
Authors: KIDD D. A. A. , SMITH G. H.
Published: July 2012

Compounds structurally related to known amoebicidal dichloroacetamides were examined for activity against Entamoeba histolytica by an in vivo/in vitro method and an experimental caecal infection in weanling rats. Dichloro‐N‐2‐hydroxyethyl‐N‐p‐methylsulphonylbenzylacetamide (M&B 4321) was the first compound of this series to show high amoebicidal activity against experimental E. histolytica infections in young rats. Some subsequent compounds, particularly several closely related to M&B 4321, had a similar effect. Comparative experiments on both activity and toxicity were carried out on M&B 4321 and diloxanide, since the latter compound had already been administered safely to man and had shown good activity against non‐dysenteric amoebiasis. The two compounds were found to be generally similar in properties. Other compounds which were of the same order of activity were discovered later, but as none had much more activity than M&B 4321 they were not studied in detail. A small trial against dysenteric amoebiasis showed that M&B 4321 was amoebicidal in man but that the cure rate was disappointing.
OBSERVATIONS ON THE SUBSTRATE SPECIFICITY OF DOPA DECARBOXYLASE FROM OX ADRENAL MEDULLA, HUMAN PHAEOCHROMOCYTOMA AND HUMAN ARGENTAFFINOMA
Authors: HAGEN P.
Published: July 2012

The substrate specificity of the dopa decarboxylases of ox adrenal medulla, human phaeochromocytoma and human argentaffinoma have been studied. The enzymes from all three tissues decarboxylated dopa, metatyrosine, orthotyrosine and 5‐hydroxytryptophan. Dopa was decarboxylated most rapidly and 5‐hydroxytryptophan least rapidly by the enzyme from all three tissues. Competition experiments indicate that all four substrates are decarboxylated by the one enzyme. Attempts to demonstrate decarboxylation of [C14]‐tyrosine, [C14]‐tryptophan or [C14]‐histidine by these enzyme preparations were unsuccessful.
EFFECT OF ADRENALINE INFUSIONS ON THE CATECHOL AMINE CONTENT OF CAT AND RAT TISSUES
Authors: HARVEY JUDITH A. , PENNEFATHER JOCELYN N.
Published: July 2012

Infusions of adrenaline failed to produce a significant increase in the adrenaline and noradrenaline content of cat uterus and kidney and of rat uterus and spleen, using normal and reserpine‐treated animals. The adrenaline content of extracts of the organs was assayed on the isolated rat uterus, which was stimulated electrically; the noradrenaline content was assayed on the blood pressure of the pithed rat. The tissues studied contained relatively small quantities of adrenaline and this was not decreased by reserpine. Our results show a difference between the stores of adrenaline and noradrenaline in these tissues; the noradrenaline stores are larger, they are depleted by reserpine, and they are increased by an infusion of noradrenaline.
ACTIONS OF SOME ANTICHOLINESTERASES ON THE SMOOTH MUSCLE OF THE CHICK AMNION
Authors: CUTHBERT A. W.
Published: July 2012

The actions of both reversible and irreversible anticholinesterase drugs on the nerve‐free smooth muscle of the chick amnion are described. The tertiary compound physostigmine and the irreversible inhibitor diisopropylfluorophosphonate were found to be active in causing contractions, whereas the quaternary compound neostigmine and the irreversible inhibitor Mipafox were only slightly active in this respect. Manometric studies showed that all four compounds were highly active, however, in inhibiting the cholinesterase found in the chick amnion. The effects produced by these compounds in the organ bath are thought to be due to the accumulation of endogenously produced acetylcholine within the tissue. Evidence for an intracellular action of endogenously produced acetylcholine in the smooth muscle of the chick amnion is discussed.
EFFECT OF CHLORPROMAZINE AND RESERPINE ON THE CATECHOL AMINE CONTENT OF DIFFERENT AREAS OF THE CENTRAL NERVOUS SYSTEM OF THE DOG
Authors: MALHOTRA C. L. , PRASAD K.
Published: July 2012

The effects of chlorpromazine and reserpine on the noradrenaline and adrenaline contents of the frontal cortex, the hypothalamus, the hippocampus and the midbrain were studied in the dog. In control dogs, the catechol amine concentrations were highest in the hypothalamus and lowest in the frontal cortex and the hippocampus. Noradrenaline contents were about seven to nine times as high as those of adrenaline in all the areas. Small doses of chlorpromazine raised the catechol amines in all the areas, the rise being maximum with 5 mg/kg. With increase in the dose of chlorpromazine there was a gradual reversal of the effect and, with 25 mg/kg, there was diminution of noradrenaline content in all the areas except in the hypothalamus. In general, chlorpromazine produced a greater rise in adrenaline than it did of noradrenaline content, and the increase of both amines was very high in the midbrain and the hippocampus compared with the other areas. Reserpine, however, depleted the catechol amine contents of all areas. The depletion was greatest for noradrenaline, an effect quite marked in the midbrain and the frontal cortex. It was concluded that the actions of these two tranquillizers on the catechol amines of dog brain differed both as to site and mechanism.
DISPOSITION OF [35S]‐HEPARIN IN THE RAT
Authors: DAY MARGARET , GREEN J. P. , ROBINSON J. D.
Published: July 2012

[35S]‐Heparin is rapidly taken up by tissues after intraperitoneal injection and rapidly degraded. Skin, aorta and lung showed an especially high affinity for [35S]‐heparin. In these organs, as well as in adrenal gland, stomach, heart and brain, the isotope was found preponderantly as dialysable metabolite(s) of heparin. Another group of tissues (large intestine, fat, kidney and liver) was characterized by a smaller proportion of dialysable material. Tissues that showed a high affinity for exogenous heparin appeared to catabolize it rapidly. It is also noted that some of the radio‐active material present in tissues after the injection of [35S]‐heparin could come from the uptake of [35S]‐sulphate resulting from the degradation of [35S]‐heparin. The incorporation of [35S]‐sulphate into the sulphomucopolysaccharides of some tissues is recorded.
TRYPANOCIDAL ACTION OF p‐BIGUANIDOACETOPHENONE AMIDINOHYDRAZONE
Authors: HAWKING F.
Published: July 2012

p‐Biguanidoacetophenone amidinohydrazone, given in single doses, can cure mice infected with an old laboratory strain of Trypanosoma rhodesiense, but it has only slight action on more recently isolated strains. Trypanosomes which are resistant to stilbamidine are resistant to this compound also. Apparently its trypanocidal action is similar to that of the diamidine series of trypanocidal compounds.
PHARMACOLOGICAL ACTIONS OF PEPSITENSIN
Authors: BLAIR A. M. J. N.
Published: July 2012

In confirmation of the results of Croxatto and his co‐workers, plasma proteins incubated with pepsin yielded a substance (pepsitensin) with pressor activity. Euglobulin gave a much higher yield than the other plasma protein fractions. Incubation for 4 hr at pH 4 gave high yields of pressor activity (pepsitensin) but no antidiuretic activity; incubation of euglobulin for 4 hr at pH 2.5 yielded extracts with antidiuretic as well as pressor activity. Incubation for 8 to 11 hr at pH 2.5 produced the highest yield of both activities. Further incubation, at the same pH, up to 20 hr caused a rapid decline in the pressor activity of the extracts, but the antidiuretic activity was much more resistant to destruction by pepsin. Pepsitensin was found to be very soluble in water and poorly soluble in organic solvents. It is not inactivated by thioglycollate. In blood pressure assays some animals did not respond to pepsitensin, and nephrectomized (17 to 24 hr) rats were found to be more suitable preparations. Pepsitensin was shown to exert pressor effect by direct action on the blood vessels. Its pressor action could be differentiated from that of tyramine, dimethylphenylpiperazine, nicotine, noradrenaline and Pitressin but not from that of angiotensin. The isolated guinea‐pig ileum and the rat uterus were equally sensitive to angiotensin and pepsitensin. In paper chromatograms, in the solvent system butanol‐acetic acid‐water, the RF of pepsitensin was very similar to that of angiotensin.
ON THE MECHANISM OF ACTION OF COLISAN
Authors: BERGMANN F. , CHAIMOVITZ M. , LEON S. , PREISS B.
Published: July 2012

Purified Colisan produces instantaneous lysis of paramecia and amoebae, and blebbing of paramecia, rat mast cells and ascites tumour cells. Colisan liberates histamine from mast cells. It also suppresses competitively the bradykinin‐provoked contraction of the guinea‐pig ileum. Most of these effects are not shared by staphylococcus‐haemolysin. The results suggest a rapid change of the permeability of the cell membrane as the mechanism of all the diversified biological actions of Colisan.
DUAL ACTION OF NITROPARAFFINS ON THE GUINEA‐PIG ILEUM
Authors: BERGMANN F. , CHAIMOVITZ M. , WIND ESTHER
Published: July 2012

Nitroparaffins act on the guinea‐pig ileum by several mechanisms. They produce contraction partly by ganglionic stimulation and partly by direct liberation of transmitter from the nerve endings. They also inhibit the response to acetylcholine and nicotine, but interfere less with the action of histamine, serotonin or bradykinin. The two opposite effects of the nitro compounds are independent of each other. Within the homologous series of normal nitroparaffins, the excitatory action diminishes and the inhibitory effect increases with the lengthening of the carbon chain.
ACTION OF NICOTINE ON THE RABBIT MUSCULAR ORGAN (ILEO‐COLIC SPHINCTER)
Authors: JARRETT R. J.
Published: July 2012

The effects of nicotine on the longitudinal muscle of the rabbit muscular organ (ileo‐colic sphincter) have been studied. Nicotine in doses from 1 to 10 μg/ml. inhibits the pendular movements of the muscle. This inhibition can also be produced by acetylcholine in the presence of atropine. In both instances, the inhibitory effect can be blocked by ephedrine, hexamethonium and bretylium. Doses of hexamethonium which block the inhibitory action of nicotine reveal an excitatory action, which itself can be blocked by higher doses of hexamethonium. Bretylium blocks both actions of nicotine at the same dose level. It is suggested that nicotine produces inhibition by releasing catechol amines, the site of action being a cholinergic junction between sympathetic nerve and catechol amine store, and further that bretylium blocks the action of acetylcholine and nicotine at this site as well as at the parasympathetic ganglia.
EFFECT OF SYMPATHOMIMETIC AMINES ON THE BLOCKING ACTION OF GUANETHIDINE, BRETYLIUM AND XYLOCHOLINE
Authors: DAY M. D.
Published: July 2012

Experiments were carried out in which the adrenergic neurone blocking activity of xylocholine, bretylium and guanethidine was studied by the use of the inhibitory responses of the isolated rabbit ileum to lumbar sympathetic nerve stimulation, and the contractions of the nictitating membrane of the anaesthetized cat in response to stimulation of the cervical sympathetic nerves. In both these preparations, after blockade of the effects of sympathetic nerve stimulation had been produced with xylocholine, bretylium or guanethidine, the sympathomimetic amines, dexamphetamine, mephentermine, hydroxyamphetamine, ephedrine and phenethylamine, reversed the blockade; if these amines were given first, then the adrenergic neurone blocking agents were ineffective. Tyramine and dopamine were effective on the isolated rabbit ileum but not on the cat's nictitating membrane. Effective antagonism of the adrenergic neurone blocking drugs was also shown by some substances which inhibit mono‐amine oxidase but only those which in addition possess sympathomimetic effects. Thus phenelzine, pheniprazine and tranylcypromine were effective whereas iproniazid and nialamide were not. Since xylocholine, bretylium and guanethidine were all antagonized by the same agents, it seems likely that they all produce sympathetic blockade by a similar mechanism. The possibility is discussed that the sympathomimetic amines which antagonize the adrenergic neurone blocking drugs are competing with these substances for the same receptor sites.
COMPARISON OF BRETYLIUM AND GUANETHIDINE: TOLERANCE, AND EFFECTS ON ADRENERGIC NERVE FUNCTION AND RESPONSES TO SYMPATHOMIMETIC AMINES
Authors: BOURA A. L. A. , GREEN A. F.
Published: July 2012

Bretylium depresses the slope of regression lines relating frequency of sympathetic nerve stimulation to magnitude of contractions of the cat nictitating membrane. In contrast, guanethidine and reserpine preferentially abolish responses to low rates of nerve stimulation and cause a roughly parallel shift of the regression lines. The hypersensitivity of the nictitating membranes of cats to intravenous adrenaline or noradrenaline is far greater after a series of small daily doses of bretylium or guanethidine than after single large doses. The maximal sensitivity produced was similar to that after postganglionic sympathetic nerve section and exceeded that produced by ganglion blockade. The development of hypersensitivity to catechol amines is accompanied by some return of responses of the nictitating membranes to sympathetic nerve stimulation despite continued daily administration of bretylium or guanethidine. In cats given bretylium daily, responses to low rates of nerve stimulation become greater than in controls unless the dose of bretylium given subcutaneously is 50 mg/kg or more. When marked hypersensitivity to catechol amines has been produced by giving bretylium or guanethidine daily for 7 or 14 days, the sympathomimetic effects of these compounds are greater. Responses to intravenous dimethylphenylpiperazinium are also increased and the results suggest that even large daily doses of adrenergic neurone blocking agents do not appreciably impair the functioning of the adrenal medulla. The pressor effects of intravenous adrenaline, noradrenaline and dimethylphenylpiperazinium iodide increase less than the corresponding nictitating membrane responses. These results are discussed in relation to tolerance to adrenergic neurone blockade, and differences between the effects of bretylium and guanethidine found in man. Bretylium and guanethidine depress the slopes of the dose‐response curves for the pressor and nictitating membrane contracting effects of tyramine. When single doses or a short series of daily doses were given, guanethidine caused more depression of the slopes than did bretylium, but nevertheless large depressions of slope were found after giving bretylium daily for several weeks. The magnitude of the responses can be greater or less than in controls depending on the dose of the sympathomimetic amine, the dose of the adrenergic neurone blocking agent and the duration of its administration. The results suggest that injection of tyramine produces a progressively smaller release of adrenaline or noradrenaline during the daily administration of bretylium (or guanethidine) but that in some test situations this is more than compensated for by the development of hypersensitivity to the catechol amine released. Some corresponding changes in responses to amphetamine and ephedrine are also described.
STUDIES ON SYMPATHETIC MECHANISMS IN ISOLATED INTESTINAL AND VAS DEFERENS PREPARATIONS
Authors: BENTLEY G. A.
Published: July 2012

The effects of various drugs which block sympathetic nerves have been studied in Finkleman preparations of rabbit and cat ileum. Contractile responses could be produced in many cases after the normal inhibitory responses to periarterial nerve stimulation had been blocked. In almost all cases this contractile response was abolished by ganglion‐blocking drugs. The normal rabbit ileum Finkleman preparation was found to behave differently towards bretylium than do preparations taken from animals treated with reserpine. The block of the guinea‐pig isolated hypogastric vas deferens preparation caused by hemicholinium HC‐3 was found to be reversed in the presence of noradrenaline, histamine, or 5‐hydroxytryptamine, as was the block caused by guanethidine and bretylium. The results are discussed in relation to the Burn‐Rand theory of sympathetic nerve mechanism.
IDENTIFICATION OF THE SMOOTH MUSCLE EXCITATORY RECEPTORS FOR ERGOT ALKALOIDS
Authors: INNES I. R.
Published: July 2012

In cats under sodium pentobarbitone anaesthesia the first dose of ergotamine (50 μg/kg) invariably caused retraction of the nictitating membrane and a rise of arterial blood pressure. However, the responses to the dose of ergotamine were strikingly reduced when the cats were previously treated with the adrenaline antagonists phenoxybenzamine (5 mg/kg) or ergotamine (50 μg/kg). Further experiments to identify receptors for ergotamine were carried out on three different isolated smooth muscle preparations: rabbit aorta, rat uterus and dog retractor penis. Receptors for adrenaline were selectively protected by high concentrations of adrenaline throughout exposure of the preparation to a blocking concentration of ergotamine or phenoxybenzamine. Protected muscles responded to ergotamine; unprotected muscles did not. Muscles where receptors for acetylcholine, histamine or 5‐hydroxytryptamine were protected by high concentrations of these drugs did not respond to ergotamine. Ergometrine, which has no blocking action on adrenaline receptors, behaved in the same way as ergotamine; muscles which were protected by adrenaline against blockade by phenoxybenzamine responded to ergometrine, but unprotected muscles did not. The stimulant actions of adrenaline, ergotamine and ergometrine were also protected against the blocking action of phenoxybenzamine by treating the muscle with a high concentration of ergometrine instead of adrenaline. It is concluded that, in smooth muscle which can be excited by adrenaline, ergotamine and ergometrine act by combining with adrenaline receptors, and that ergotamine may therefore be regarded not only as an adrenaline antagonist but also as a partial agonist since it excites the same receptors.
ECTOPIC VENTRICULAR RHYTHMS AND MYOCARDIAL INFARCTION IN THE DOMESTIC PIG AND THEIR RESPONSE TO NIALAMIDE, A MONOAMINE OXIDASE INHIBITOR
Authors: ARORA R. B. , SIVAPPA D. S.
Published: July 2012

The development in Indian domestic pigs of ectopic ventricular rhythms and a low‐frequency tachycardia after the two‐stage ligature of the anterior descending branch of the left coronary artery is described. When the ligature was tied 26 ± 3 mm from the left auricular margin, the change in rhythm developed after 2 to 2.5 hr, reached a maximum after 6 hr and persisted up to 28 hr. The histopathological character of the resultant acute myocardial infarction is presented. In all, 52 pigs were used. Pretreatment of 9 pigs, with 3 as controls, with a monoamine oxidase inhibitor, nialamide, 20 mg/kg daily for 2 to 4 days, suppressed the development of experimental ventricular arrhythmia and favourably influenced the ischaemic myocardium by reducing the oedema and the formation of microthrombi. A possible mode of action involving monoamine oxidase inhibition is suggested.
INHIBITORY EFFECTS OF CARBOHYDRATES ON HISTAMINE RELEASE AND MAST CELL DISRUPTION BY DEXTRAN
Authors: BERALDO W. T. , DA SILVA W. DIAS , FERNANDES A. D. LEMOS
Published: July 2012

Alloxan diabetic rats failed to show the skin reaction (blue spot) evoked by dextran, whereas the effects produced by histamine and compound 48/80 were not altered. When dextran and glucose were injected simultaneously into the skin the reaction was inhibited. In vitro, mast cell alterations produced by dextran occurred simultaneously with histamine release; both processes were inhibited by glucose, other carbohydrates related to glucose, and inhibitors of anaphylaxis. These experiments suggest that dextran releases histamine by a mechanism similar to that found with 48/80 and anaphylaxis in the rat. The inhibitory effect of carbohydrates may be understood on the basis of a competitive mechanism.
EFFECT OF GUANETHIDINE, HEMICHOLINIUM AND MEBUTAMATE ON THE HYPERTENSIVE RESPONSE TO ESERINE AND CATECHOL AMINES
Authors: VARAGIĆ V. , VOJVODIĆ N.
Published: July 2012

Guanethidine, hemicholinium and mebutamate were used to study the site and mechanism of the hypertensive response to eserine in the rat. Guanethidine was found to block very effectively the hypertensive effect of eserine and to produce at the same time a very strong potentiation of the response to catechol amines. Hemicholinium, after a certain latent period, also blocked the effect of eserine, at the same time leaving the response to adrenaline and noradrenaline intact. Mebutamate was also found to block the effect of eserine. The results of the present experiments suggest that eserine produces a central adrenergic activation in the rat.
EFFECT OF TERATOGENIC AND RELATED DYES ON THE HAEMOGLOBIN NITRITE SENSITIVITY REACTION
Authors: METCALF W. K.
Published: July 2012

The teratogenic dyes trypan blue and Evans blue have a marked and immediate action on the oxidation stability of intracellular haemoglobin in rats. Of the proved non‐teratogenic substances tested only o‐tolidine has an effect on the haemoglobin stability, and this effect is slow. It is suggested that the effect of the teratogens on the haemoglobin oxidation sensitivity is due to interference with the protein component of the flavoprotein enzymes.