bluuebunny/crossref_metadata_2025 huggingface dataset:
THE INHIBITION OF THE PERISTALTIC REFLEX BY SUBSTANCES FROM PROTEIN SOURCES
Authors: SCHNEIDER R. , BISHOP HILARY , SHAW B.
Published: July 2012

An aqueous extract of gluten, and its ultrafiltrate, depressed the peristaltic reflex of the rat jejunum. This effect was shared by similar extracts of mammalian skeletal muscle but not by such proteins as casein, gelatin, and albumin. Peptic‐tryptic digestion did not abolish the effect, whereas acid hydrolysis of the active fractions destroyed the depressant substance.
THE ABSORPTION OF PROTHIDIUM BY TRYPANOSOMA RHODESIENSE
Authors: TAYLOR ANGELA E. R.
Published: July 2012

When rats, heavily infected with Trypanosoma rhodesiense, were injected with Prothidium and killed 1 to 5 hours later, measurable amounts of the drug could be extracted from the parasites: a million trypanosomes have been shown to absorb 0.01 to 0.06 μg. of Prothidium in vivo. When viewed with the fluorescence microscope, treated trypanosomes appeared to concentrate Prothidium particularly in the blepharoplast and other cytoplasmic granules. Prothidium was absorbed by trypanosomes in vitro in less than 30 min. When equilibrium had been reached the concentration of the drug inside the trypanosome was approximately 400 times the concentration outside, in the range of concentrations studied.
ANALGESIC ACTION OF ETHYL 4‐PHENYLPIPERIDINE‐4‐CARBOXYLATES WITH OXYGENATED 1‐SUBSTITUENTS
Authors: BLAIR A. M. J. N. , STEPHENSON R. P. ,   With an Addendum By R. E. LISTER and R. P. STEPHENSON
Published: July 2012

The analgesic potency of a series of new compounds related to pethidine has been measured in rats. The replacement of the methyl group on the nitrogen atom of pethidine by groups containing ether linkages produces an increase in potency. Two different positions for the oxygen atom are particularly beneficial, but the effects, in these two positions, appear to be exerted in different ways and are not additive. Simple toxicity tests in mice and rats and tests on respiration in rats of five of the more potent compounds revealed no unexpected adverse action.
PHARMACOLOGICAL ACTIONS OF TWO NEW PETHIDINE ANALOGUES
Authors: LISTER R. E.
Published: July 2012

The behaviour of two new analgesics, benzethidine and furethidine, in a number of different tests has been compared with that of pethidine. Some differences in side‐effects at equi‐analgesic dosage were observed, particularly a reduction in histamine release.
THE SELECTIVE ACCUMULATION OF BRETYLIUM IN SYMPATHETIC GANGLIA AND THEIR POSTGANGLIONIC NERVES
Authors: BOURA A. L. A. , COPP F. C. , DUNCOMBE W. G. , GREEN A. F. , McCOUBREY A.
Published: July 2012

A study of the distribution of [14C]‐labelled bretylium (N‐o‐bromobenzyl‐N‐ ethyl‐N,N‐dimethylammonium) in cat tissues at various times after subcutaneous injection suggests that the specificity of its blocking action on adrenergic neurones may be related to its selective accumulation in these neurones. The rate of rise and fall of concentration in sympathetic ganglia and postganglionic sympathetic nerves showed a close similarity to the time course of the blocking adrenergic neurones as manifested by relaxation of the nictitating membranes. Concentrations found were similar to those in adrenergic nerve trunks when topical application of the drug had caused a local block of conduction. Conduction in other types of nerve could be blocked by topical application, but in general they were less sensitive, heavily myelinated nerves being the most resistant.
THE RELATIONSHIP BETWEEN THE CHEMICAL STRUCTURE AND NEUROTOXICITY OF ALKYL ORGANOPHOSPHORUS COMPOUNDS
Authors: DAVIES D. R. , HOLLAND P. , RUMENS M. J.
Published: July 2012

Thirty‐six alkyl organophosphorus compounds have been tested for neurotoxicity in the chicken. The individual compounds were chosen to enable the importance of each portion of the molecule to be assessed in relation to the property of neurotoxicity. Seventeen substances were found to be neurotoxic, fifteen for the first time. All of these contained fluorine. On the basis of the results reported, certain predictions have been made about the chemical structure of compounds which would be expected to be neurotoxic. The importance of fluorine suggests that it plays a direct role in the development of the biochemical lesion, and this may occur as the result of its being carried by the molecule as a whole to specific areas in the nervous system. By the action of cholinesterase, the P‐F bond may be ruptured and ionic fluorine liberated where it blocks some metabolic cycle.
THE BRONCHOCONSTRICTOR ACTION OF BRADYKININ IN THE GUINEA‐PIG
Authors: COLLIER H. O. J. , HOLGATE J. A. , SCHACHTER M. , SHORLEY PATRICIA G.
Published: July 2012

Bradykinin was found to be a potent bronchoconstrictor agent in the guinea‐pig anaesthetized with urethane. This action was not affected by vagotomy, or by treatment of the animal with mepyramine, atropine, lysergic acid diethylamide, or cortisone. Adrenaline and isoprenaline suppressed the bronchoconstrictor responses to bradykinin and histamine. Small doses of acetylsalicylic acid, however, suppressed only that to bradykinin. Bradykinin also produced bronchoconstriction in the isolated perfused lungs of the guinea‐pig. The closely related peptide, wasp kinin, was also a potent bronchoconstrictor.
THE PHARMACOLOGY OF CHYMOTRYPSIN ADMINISTERED BY INHALATION
Authors: GOLBERG L. , MARTIN L. E. , SHEARD P. , HARRISON C.
Published: July 2012

The ability of chymotrypsin to reach the limits of the bronchial tree has been studied in cats receiving the enzyme by inhalation as a very fine powder. For this purpose derivatives of chymotrypsin were used which had been labelled with a fluorescent molecule or with [131I]. Quantitative measurements of the absorption and distribution of inhaled chymotrypsin‐ [131I] revealed a rapid removal of radioactivity from the lungs over the first 24 hr. and corresponding excretion of labelled inorganic iodide in the urine. High levels of activity were not attained in the blood or thyroid. Subcutaneous administration of labelled enzyme led to more rapid accumulation of radioactivity in the blood and thyroid. Consideration of these and other results leads to the conclusion that, while some enzyme ascends the respiratory tract by ciliary movement of mucus, a substantial part is absorbed into the lungs and the [131I] subsequently detached from it.

The changes in tidal air accompanying inhalation of labelled trypsin and chymotrypsin were followed in anaesthetized cats. Trypsin brings about a decrease in tidal air in distinctly lower doses than does chymotrypsin. Prior administration of mepyramine had an antagonistic effect, and it is suggested that the change in tidal air is essentially the result of bronchial spasm.
THE EFFECT OF ENZYME INHIBITORS ON HISTAMINE CATABOLISM IN MAN
Authors: LINDELL S. E. , NILSSON KAREN , ROOS B.‐E. , WESTLING H.
Published: July 2012

The catabolism of histamine was studied in three female psychiatric patients by analysis of the [14C]‐labelled metabolic products occurring in the urine after a subcutaneous injection of [14C]histamine. Each patient was studied before and during treatment with aminoguanidine or iproniazid.

Without treatment the patients had a normal histamine catabolism. Aminoguanidine and iproniazid inhibited the oxidation of histamine to imidazoleacetic acid; iproniazid produced a 50% inhibition of the oxidation of methylhistamine to methylimidazoleacetic acid. After iproniazid a large proportion of the injected [C14]histamine was excreted as methyl [14C]histamine.
THE ANTI‐ANAPHYLACTIC AND HISTAMINE‐RELEASING PROPERTIES OF THE ANTIHISTAMINES. THEIR EFFECT ON THE MAST CELLS
Authors: MOTA I. , DA SILVA W. DIAS
Published: July 2012

It has been shown that, depending upon their concentration, antihistamines act in three different ways: (a) by competitive inhibition of histamine as already known; (b) by destroying mast cells and releasing histamine; and (c) by preventing mast cell damage and histamine release in anaphylaxis. Furthermore, antihistamines potentiated mast cell damage and histamine release by compound 48/80, when acting on guinea‐pig tissues, and inhibited these same phenomena when acting on rat tissues. It is concluded that the effect of antihistamines in anaphylaxis is possibly due both to their competitive inhibition of histamine on smooth muscle receptors and to their inhibition of mast cell damage and histamine release by antigen.
A NEW BIOLOGICAL METHOD FOR THE ASSAY OF DEPOLARIZING SUBSTANCES USING THE ISOLATED SEMISPINALIS MUSCLE OF THE CHICK
Authors: CHILD K. J. , ZAIMIS ELEANOR
Published: July 2012

The isolated semispinalis cervicis muscle of a 3 to 10 days old chick has been found to provide a very useful assay method for depolarizing substances. There are three main advantages of this preparation over that of the rectus abdominis of the frog: (a) quick relaxation without any artificial stretching of the muscle, (b) greater sensitivity to depolarizing drugs, and (c) no falling off in sensitivity for at least 2 hr.
SCREENING OF CESTICIDAL COMPOUNDS ON A TAPEWORM HYMENOLEPIS NANA IN VITRO
Authors: SEN A. B. , HAWKING F.
Published: July 2012

A simple and convenient in vitro technique is described for the screening of compounds for action against Hymenolepis nana and probably many other intestinal worms. The results obtained from this test are in broad agreement with the findings of clinical experience and of a small series of in vivo tests. Among the substances tested, the most active ones were oil of chenopodium, dichlorophen, extract of cashew nut (Anacardium occidentale), antimony potassium tartrate, and BIQ 20 [eicosamethylenebis(isoquinolinium iodide)].
THE RESPONSE OF ISOLATED RABBIT ATRIA TO ACONITINE
Authors: YELNOSKY JOHN , CLARK BYRON B.
Published: July 2012

The arrhythmias observed in isolated rabbit atria appear to be due to two actions of aconitine. One is an apparent direct stimulant effect on the sino‐atrial node and the other is a depressant effect on the processes involved in intra‐atrial propagation of impulses. Acetylcholine has either an inhibitory or stimulatory effect on atria pretreated with aconitine because it antagonizes the actions of aconitine both on the sinus node and on conduction. When conduction block is not apparent, acetylcholine depresses the atrial rate. On the other hand, when conduction is markedly depressed, acetylcholine increases the atrial rate.
ANAESTHESIA IN NEW‐BORN ANIMALS
Authors: WEATHERALL JOSEPHINE A. C.
Published: July 2012

Pentobarbitone was more toxic to new‐born than to adult rabbits and rats, produced a longer loss of righting reflex in new‐born animals but did not anaesthetize them effectively in less than toxic doses. Urethane did not anaesthetize new‐born animals in doses which anaesthetized adults. Ether produced loss of righting reflex at lower concentrations for new‐born than for adults, but the new‐born animals became anaesthetized more slowly.
THE EFFECT OF HEXAMETHONIUM ON THE CAROTID CHEMORECEPTOR RESPONSE TO NICOTINE AND CYANIDE
Authors: BYCK R.
Published: July 2012

The literature concerning the effects of ganglionic blocking agents on the chemoreceptors is reviewed. Hexamethonium blocks the respiratory response to intracarotid injections of small doses of nicotine in dogs anaesthetized with chloralose, but it does not block the response to sodium cyanide.
EFFECT OF SEX HORMONES ON THE EXCRETION OF FREE HISTAMINE BY MALE AND FEMALE RATS
Authors: MARSHALL P. B.
Published: July 2012

The excretion of free histamine by male rats was increased 10‐fold by treatment with oestrogen or castration. That of female rats was reduced to 1/10 by treatment with testosterone. Ovariectomy further increased the histamine excretion by female rats, which was slightly reduced by treatment with oestrogen, and at oestrus. The low level of free histamine excretion by male rats was not increased by compound SKF 525‐A, and inhibition of diamine oxidase by aminoguanidine caused the same proportionate increase in both sexes. It is concluded that the conjugation of histamine by male rats requires the presence of androgens, and some preliminary indication is given regarding the possible mechanisms involved.
THIOXANTHINES WITH POTENT BRONCHODILATOR AND CORONARY DILATOR PROPERTIES
Authors: ARMITAGE A. K. , BOSWOOD JANET , LARGE B. J.
Published: July 2012

Some of the pharmacological properties of two new compounds, choline 6‐thiotheophyllinate and the choline salt of 3‐isobutyl‐1‐methyl‐6‐thioxanthine (M&B 5924), are described. Both these 6‐thioxanthines are structurally related to theophylline and pharmacologically they are very similar to that compound, the main differences in their actions being essentially quantitative. They were more potent than choline theophyllinate as bronchodilators on the isolated guinea‐pig tracheal ring preparation and as coronary dilators on the dog heart‐lung preparation. Choline 6‐thiotheophyllinate was about as effective as its oxygen analogue in protecting guinea‐pigs against the lethal effects of a bronchoconstrictor aerosol; M&B 5924 was more effective in this respect, but the relative bronchodilator activity was much less than on the isolated preparation. Both thioxanthines were less potent than choline theophyllinate as diuretics. One outstanding qualitative difference in their properties was in their effect on the voluntary motor activity of mice; choline theophyllinate in low doses was stimulant whereas the thioxanthines were either inactive at low doses or sedative at higher doses. In dogs, on the other hand, there were indications that M&B 5924 had a stimulant action.
THE FORMATION OF AN ISOPRENALINE‐LIKE SUBSTANCE FROM ADRENALINE
Authors: EAKINS K. E. , LOCKETT MARY F.
Published: July 2012

Intravenous injections of adrenaline, but not those of noradrenaline, caused the appearance of a substance which resembled isoprenaline in RF value and pharmacological activity in blood withdrawn from the lower abdominal aortae of chloralosed cats rested after acute adrenalectomy and induction of lasting block in autonomic ganglia with hexamethonium. The formation of the isoprenaline‐like compound was prevented by pretreatment with pyrogallol but not by pretreatment with reserpine, cocaine, phentolamine, dibenamine, harmaline, or iproniazid. The liver proved a main site of the origin of this isoprenaline‐like substance.
THE PERSISTENCE OF A DEPRESSOR RESPONSE TO OXYTOCIN IN THE FOWL AFTER DENERVATION AND BLOCKING AGENTS
Authors: LLOYD SYBIL , PICKFORD MARY
Published: July 2012

The effects of oxytocin and vasopressin on the blood pressure of the fowl have been studied after surgical or chemical interruption of parts of the central and peripheral nervous systems, and after the administration of stilboestrol and progesterone. An augmented and prolonged depressor response to oxytocin was seen after atropine, bretylium, tetraethylammonium or decapitation, but not after decerebration, dihydroergotamine or dibenamine. There was a tendency for the pressor action of vasopressin to disappear after decapitation, decerebration, and all the blocking agents used, except tetraethylammonium. The differences between these results and those which have been obtained in rats are discussed.
ANTAGONISM OF APOMORPHINE‐INDUCED PECKING IN PIGEONS
Authors: DHAWAN B. N. , SAXENA P. N. , GUPTA G. P.
Published: July 2012

Central nervous system stimulants, tranquillizers and other central nervous system depressants, antiemetics, antihistamine drugs and autonomic blocking agents were examined for their ability to prevent the pecking response in pigeons induced by apomorphine (250 μg/kg intramuscularly). Reduction in the proportion of positive responses or significant increase in the latent period of pecking were taken as the criterion of effectiveness. Protection was afforded by caffeine, lysergic acid diethylamide, morphine, rauwolscine, triflupromazine and yohimbine. In addition, a significant increase in latent period was produced by artane, pentobarbitone, benactyzine, 2‐bromolysergic acid diethylamide, cyclizine, diphenhydramine, ergotoxine, hyoscine, promethazine, 5‐(2‐chloroethyl)‐4‐methylthiazole and trimethobenzamide. Most of these drugs influenced the pecking and emetic responses to apomorphine in an identical manner. It is possible that identical receptors may be concerned with apomorphine pecking (in pigeons) and emesis (in other species).
EFFECTS ON AMINE OXIDASE OF SUBSTANCES WHICH ANTAGONIZE 5‐HYDROXYTRYPTAMINE MORE THAN TRYPTAMINE ON THE RAT FUNDUS STRIP
Authors: BARLOW R. B.
Published: July 2012

Certain substances, 2‐bromolysergic acid diethylamide, dimethyltryptamine (3‐(2‐dimethylaminoethyl)indole), 2‐methyldimethyltryptamine (3‐(2‐dimethylaminoethyl)‐2‐methylindole), and 5‐benzyloxydimethyltryptamine (5‐benzyloxy‐3‐(2‐dimethylaminoethyl)indole), antagonize the effects of 5‐hydroxytryptamine on the rat fundus strip more than those of tryptamine. These substances have been tested for their ability to inhibit the oxidation of tryptamine and 5‐hydroxytryptamine by suspensions of guinea‐pig liver and rat fundus. 2‐Bromolysergic acid diethylamide has virtually no inhibitory activity and it is doubtful if the others produce any significant inhibition of amine oxidase in the concentrations which antagonize the effects of 5‐hydroxytryptamine more than those of tryptamine. It seems that the differential character of the blocking action of these compounds should be ascribed either to interference with the transport of tryptamine (but not 5‐hydroxytryptamine) through the cell wall, coupled with the block of a receptor common to both tryptamine and 5‐hydroxytryptamine, or to the existence of separate tryptamine and 5‐hydroxytryptamine receptors.

The amine oxidases of the guinea‐pig liver and rat fundus appear to be a mixture of at least two types of enzyme, one of which has a higher affinity for 5‐hydroxytryptamine than the other and is more susceptible to inhibition by 2‐methyldimethyltryptamine.
RESPONSES OF THE ISOLATED SYMPATHETIC NERVE‐DUCTUS DEFERENS PREPARATION OF THE GUINEA‐PIG
Authors: HUKOVIĆ S.
Published: July 2012

An isolated ductus deferens preparation together with the sympathetic hypogastric nerve of the guinea‐pig is described. While the preparation showed no spontaneous contractions, nerve stimulation produced longitudinal contractions. The responses to successive periods of nerve stimulation remained constant for several hours. After noradrenaline had been added to the bath fluid for 30 min and then the fluid repeatedly changed to wash out the noradrenaline, the effect of nerve stimulation was greatly increased but declined in the course of 1 hr to the original height. Cocaine also increased the response to stimulation. Preparations made from guinea‐pigs which had previously received reserpine responded to nerve stimulation with progressively diminishing contractions. In these circumstances, the administration of noradrenaline restored the response to nerve stimulation to that seen originally.
EFFECT OF DOPAMINE ON THE ISOLATED PERFUSED LUNG LOBES OF THE DOG
Authors: WAALER BJARNE A.
Published: July 2012

Dopamine (β‐3:4‐dihydroxyphenylethylamine) has a pressor action on the pulmonary vascular bed in isolated perfused lung lobes of the dog. Its pulmonary vasoconstrictor effect in this preparation is about 1/20–1/30 that of adrenaline or noradrenaline. When compared with adrenaline, dopamine is less effective as a vasoconstrictor in the bronchial vascular system than in the pulmonary circulation. Even very large doses of dopamine had no bronchomotor effect in the isolated perfused lung lobes. Addition of dopamine alone, or of dopamine together with some “new” blood, sometimes caused a potentiation of the pulmonary vasoconstrictor responses to sympathetic nerve stimulation.
LOCALIZATION OF CHOLINESTERASES IN THE CHICKEN NERVOUS SYSTEM AND THE PROBLEM OF THE SELECTIVE NEUROTOXICITY OF ORGANOPHOSPHORUS COMPOUNDS
Authors: CAVANAGH J. B. , HOLLAND P.
Published: July 2012

Using the thiocholine method, a restricted survey has been made of cholinesterases in the spinal cord and brain stem of the chicken. No simple relation between sites of selective damage in organophosphorus neurotoxicity and centres of cholinesterase activity could be adduced. Moreover, no significant differences between species susceptible and insusceptible to poisoning by these compounds were found by this method. It is concluded that, while cholinesterase may well play an intermediary role in the intoxication, other factors determine the selective damage to certain neurones and their processes.
ACTIONS OF AMINO‐ACIDS ON THE ISOLATED HEMISECTED SPINAL CORD OF THE TOAD
Authors: CURTIS D. R. , PHILLIS J. W. , WATKINS J. C.
Published: July 2012

The actions of a series of amino‐acids related to γ‐aminobutyric acid and glutamic acid have been determined upon the isolated and sagittally hemisected spinal cord of the toad, Bufo marinus. Slow and fast components of the ventral root reflex responses following dorsal root stimulation were depressed by γ‐aminobutyric acid and by a series of neutral amino‐acids having a similar structure. The relative depressant potencies of the members of this series were determined by comparison of the concentrations of each required to cause the same reduction in the electrically integrated slow components of these reflex responses. Glutamic acid and closely related substances facilitated reflex responses in low concentrations and depressed these responses in high concentrations. The actions of these substances resulted in the depolarization of motoneurones which was recorded as a negative potential in the ventral root. The relative potencies of the substances were estimated from the concentrations of each required to produce negative potentials of the same magnitude.

Several amino‐acids not previously tested proved to have remarkably strong actions on this preparation. 3‐Aminopropanesulphonic acid was the most potent depressant tested; homocysteic acid and n‐methylaspartic acid were the most powerful excitatory substances. The d forms of optically active depressants or excitants were always stronger than the corresponding l forms where both enantiomorphs were available. Points of similarity and dissimilarity between these results and those of related investigations are discussed.
SUPERSENSITIVITY OF SALIVARY GLANDS FOLLOWING TREATMENT WITH BRETYLIUM OR GUANETHIDINE
Authors: EMMELIN N. , ENGSTRÖM J.
Published: July 2012

The sensitivity of the submaxillary glands to noradrenaline was estimated once a week in cats anaesthetized with hexobarbitone. Daily subcutaneous injections of bretylium or guanethidine were found to produce a supersensitivity of the glands, similar to that caused by extirpation of the superior cervical ganglion.
EFFECT OF NORADRENALINE ON THE ACTION OF NICOTINE AND TYRAMINE ON ISOLATED ATRIA
Authors: AZARNOFF D. L. , BURN J. H.
Published: July 2012

Both nicotine (in the presence of atropine) and tyramine cause a rise in the rate of isolated rabbit atria. When noradrenaline is allowed to act on the atria for 20 to 30 min and then removed from the bath by repeated changes of the bath fluid, the action of nicotine and of tyramine is greatly increased. The first addition of noradrenaline to the bath often has a much smaller effect on the response to nicotine or to tyramine than have later additions. Sometimes the greater effect after the addition of nicotine persists for 2 or 3 hr. When reserpine is added to the bath and left in contact with the atria for 1 to 2 hr, and is then removed from the bath, the effect of noradrenaline on the atrial rate is much reduced in size and duration. Bretylium abolishes the action of nicotine but increases the action of tyramine.
MULTIPLE TOE‐PINCH METHOD FOR TESTING ANALGESIC DRUGS
Authors: COLLIER H. O. J. , WARNER B. T. , SKERRY RITA
Published: July 2012

In guinea‐pigs and rats, an immediate squeak was one of the most consistent and readily observed responses to application of a light artery clip to the base of a toe. Morphine and related drugs suppressed this response. Squeak‐responses from each toe of an experimental animal formed the basis of a technique for measuring activity of analgesic drugs. A statistical method was developed to analyse the correlated quantal observations obtained. It provided an estimate of the increase of information from several toes compared with one. Testing all toes of each animal yielded a substantial increase of information, because the correlation between responses of different toes was low. Among drugs having an analgesic action in man, 1‐(β‐diethyl‐aminoethyl)‐2‐(p‐ethoxybenzyl)‐5‐nitrobenzimidazole, methadone, morphine, pethidine and codeine (in descending order of potency) were active in this test in guinea‐pigs. Acetylsalicylic acid, amidopyrine, amphetamine, chlorpromazine, 4‐hydroxyisophthalic acid, lysergic acid diethylamide, mephenesin, nalorphine, pentetrazole, phenobarbitone, phencyclidine, phenytoin, salicylamide, strychnine and troxidone showed little or no activity. The time‐courses of active drugs were estimated, and morphine had the longest action.
PHARMACOLOGY OF METHICILLIN
Authors: ACRED P. , BROWN D. M. , TURNER D. H. , WRIGHT D.
Published: July 2012

The pharmacology of a new antibiotic methicillin, 6(2:6‐dimethoxybenzamido)‐penicillanic acid, which is effective against staphylococci resistant to penicillin G, has been investigated. It is free from acute and chronic toxic effects, except that some pain may be caused following intramuscular injection. It is poorly absorbed orally, but after intramuscular injection the concentrations in the serum and in tissues are very similar to those found with penicillin G. It is excreted by the kidneys both by renal tubular secretion and glomerular filtration. It is also excreted in the bile in very high concentrations, the ratio of concentration in the bile to the blood being approximately 2.5 times that of penicillin G. From a study of the metabolism of the drug it is calculated that 75% is eliminated unchanged in the urine and that the remainder is probably destroyed after the excretion into the intestine via the bile.
RATE OF ANTAGONISM OF TUBOCURARIN BY POTASSIUM IONS
Authors: CREESE R. , TAYLOR D. B. , TILTON B.
Published: July 2012

The rate at which potassium ions antagonized the neuromuscular block produced by tubocurarine has been examined in isolated rat diaphragm muscle preparations. The half‐time was dependent on the thickness of the muscle. In thick muscles (550 to 650 μ) the rate of action could be largely accounted for by the time which the potassium took to diffuse through the interstitial fluid to produce an increase in concentration in the immediate environment of the muscle fibre.
ANALGESIC‐ANTIPYRETIC DRUGS AS INHIBITORS OF KALLIKREIN
Authors: NORTHOVER B. J. , SUBRAMANIAN G.
Published: July 2012

The production of kallidin from guinea‐pig and ox serum kallidinogen by the action of guinea‐pig serum‐kallikrein or human salivary kallikrein was inhibited by various analgesic‐antipyretic drugs. This effect was obtained in vitro with concentrations of inhibitors which do not inhibit the smooth‐muscle‐stimulating action of the various polypeptides, but similar to the concentrations needed in vivo to obtain an anti‐inflammatory action. The vasodepressor action of intravenously administered human salivary kallikrein in the anaesthetized dog was very markedly inhibited by the intravenous administration of doses of various analgesic‐antipyretic drugs which only partially antagonized the responses to kallidin and bradykinin and which left the vasodepressor responses to histamine, acetylcholine and 5‐hydroxytryptamine unaffected. In rabbits the accumulation of protein‐bound dye at the site of intradermal injection of human salivary kallikrein and guinea‐pig serum‐kallikrein, but not of bradykinin and kallidin, was inhibited very markedly by the systemic administration of various analgesic‐antipyretic drugs.
RELEASE OF OXYTOCIN IN UNANAESTHETIZED LACTATING RATS
Authors: CHAUDHURY R. R.
Published: July 2012

The action of certain substances on the release of oxytocin has been studied in unanaesthetized lactating rats. The release of oxytocin has been assessed by the increase in weight after suckling of rats separated overnight from the mother. A large variety of substances appear to block the release of oxytocin. These include pentolinium, atropine and chlorpromazine. Adrenaline and noradrenaline also cause a block in the release of oxytocin, and it is suggested that adrenaline blocks the central release of oxytocin as well as blocking its peripheral action. Reserpine and oestradiol in the doses administered did not block the release of oxytocin. Block also occurred after the ingestion of water, ethanol and normal saline, an effect which may be produced indirectly by impulses from the gastro‐intestinal tract.
ANTHELMINTIC ACTIVITY OF METHYRIDINE AGAINST EXPERIMENTAL NEMATODE INFECTIONS IN MICE
Authors: BROOME A. W. J. , GREENHALGH N.
Published: July 2012

Critical studies using mice infected experimentally with nematodes (Nematospiroides dubius, Nippostrongylus muris and Heterakis spumosa) have shown methyridine to be an extremely effective anthelmintic when administered orally or subcutaneously. Comparisons of the two treatment regimes show subcutaneous administration to be the more efficient in terms of absolute dose, but neither treatment has a significant advantage in therapeutic safety margin. Methyridine has a more uniform anthelmintic action than either phenothiazine or bephenium against adult forms of the three test nematodes. In addition the drug possesses activity against all stages of certain immature nematode infections.
STUDIES ON A NEW INTRAMUSCULAR HAEMATINIC, IRON‐SORBITOL
Authors: LINDVALL S. , ANDERSSON N. S. E.
Published: July 2012

A new iron preparation for intramuscular use is described. It contains a complex of iron, sorbitol and citric acid. Its properties in comparison with several other complexes, particularly iron‐dextran, have been studied. The preparation is stable in serum, is hypertonic, does not produce haemolysis, and affects coagulation only at very high concentrations, such as are reached only in vitro. Absorption from muscle takes place very rapidly; two‐thirds of the iron is removed within 3 hr, and there is a very rapid increase in the serum‐iron concentration. In experimental animals, the maximum level is reached after about 20 min and in man after about 2 hr. Disappearance from the serum takes place rapidly. The preparation contains a small amount of a fraction which reacts with transferrin and is dialysable. In man, about 30% of the total dose of iron is excreted through the kidneys during the first 24 hr after injection, the greater part of the excretion taking place during the first few hours.
EXCRETION AND RE‐EXCRETION OF A BROAD‐SPECTRUM PENICILLIN IN BILE
Authors: STEWART G. T. , HARRISON PATRICIA M.
Published: July 2012

A technique is described for estimating the biliary excretion, reabsorption and re‐excretion of an antibacterial drug in rats. d(—)‐6‐(α‐Amino‐α‐phenylacetamido)‐penicillanic acid (BRL 1341) is rapidly excreted and re‐excreted in the bile, in concentrations bactericidal to Salmonellae and other organisms which are usually refractory to antibacterial drugs in this situation. Recoveries of the drug accounted for 20 to 30% of oral or parenteral doses; much of the remainder is probably destroyed in the gut. Results from one patient indicate that d(—)‐6‐(α‐amino‐α‐phenylacetamido)‐penicillanic acid is excreted in high concentration also in human bile.
EXCRETION OF ANTIBIOTICS IN BILE
Authors: HARRISON PATRICIA M. , STEWART G. T.
Published: July 2012

The excretion of antibiotics in the bile of rats has been studied. Penicillins, including derivatives of 6‐aminopenicillanic acid, are rapidly excreted, reabsorbed and re‐excreted, in high concentration, whereas streptomycin, neomycin, paramomycin and chloramphenicol reach lower levels in the bile than in the plasma. p‐Aminobenzylpenicillin and d(—)‐6‐(α‐amino‐α‐phenylacetamido)penicillanic acid, both of which are bactericidal to Salmonellae and other conforms, produce higher concentrations in the bile than benzylpenicillin (penicillin G). This may be of therapeutic importance.
EFFECT OF CHLORPROMAZINE ON SEPTAL HYPERACTIVITY IN THE RAT
Authors: RAITT J. R. , NELSON J. W. , TYE A.
Published: July 2012

The effect of chlorpromazine on the overt emotional activity of a hybrid strain of rats has been measured using an altered “emotionality rating scale.” It has been found that 8 mg/kg of chlorpromazine intraperitoneally reduced the activity of rats with the septal nuclei destroyed, normal rats and control rats to the same emotional rating. This effect has been related to the postulated interrelationship of the septal area and the amygdaloid complex of nuclei. It seemed that impulses traversing the septal nuclei might be re‐routed, so that destruction of the septal area need not necessarily cause total abolition of “septal‐function.”
EFFECT OF THYROID HORMONES ON HISTAMINE FORMATION IN THE RAT
Authors: BJURÖ T. , WESTLING H. , WETTERQVIST H.
Published: July 2012

Treatment with thyroxine or liothyronine increased the urinary excretion of free histamine in male and female rats under the influence of aminoguanidine, a histaminase inhibitor. There was no evidence for an altered catabolism of histamine in rats treated with liothyronine, since the same percentage of subcutaneously injected [14C]‐histamine appeared unchanged in the urine. After subcutaneous injection of [14C]‐L‐histidine, rats treated with liothyronine excreted more [14C]‐histamine than control rats. An increased formation of [14C]‐histamine from [14C]‐histidine could also be demonstrated in vitro, in the glandular portion of the stomach, while no increase was found in the skin.
SYNTHETIC OXYTOCIN AS AN ANTAGONIST OF EXPERIMENTAL CARDIAC ANOXIC CHANGES IN RABBITS
Authors: MELVILLE K. I. , VARMA D. R.
Published: July 2012

Synthetic oxytocin (Syntocinon) can be shown to reduce or abolish ST‐T changes induced experimentally by hypoxaemia alone, by hypoxaemia and ergometrine, by vasopressin, and by a new procedure involving injection of small doses of picrotoxin into the lateral cerebral ventricle. Ventricular fibrillation induced by picrotoxin can also be reversed by oxytocin. These effects suggest a probable metabolic action of oxytocin against cardiac anoxic changes, and its possible therapeutic usefulness as an antagonist of myocardial ischaemia. It is speculated that this might be a physiological action of the hormone.
EFFECT OF GUANETHIDINE IN REVEALING CHOLINERGIC SYMPATHETIC FIBRES
Authors: DAY M. D. , RAND M. J.
Published: July 2012

Guanethidine abolished the inhibitory response of segments of rabbit intestine to stimulation of the sympathetic nerves which accompany the mesenteric arteries. In the majority of experiments a motor response of the intestinal segment was then revealed; it was more readily observed in intestinal segments from young than from adult rabbits. The motor response of the intestine to sympathetic stimulation after guanethidine was blocked by atropine. It was not blocked by hexamethonium and was present in rabbits in which the vagal innervation to the small intestine had been sectioned. In the cat isolated atria, guanethidine blocked the accelerator response to sympathetic nerve stimulation and revealed a response resembling that to stimulation of the vagus. It was concluded that guanethidine blocked the release of noradrenaline and thus revealed the response to the direct action of acetylcholine released from cholinergic sympathetic nerves.
SOME EFFECTS OF A MONOAMINE OXIDASE INHIBITOR UPON CHANGES PRODUCED BY CENTRALLY ADMINISTERED AMINES
Authors: SCHAIN R. J.
Published: July 2012

In cats treated with subcutaneous or intraperitoneal injections of the monoamine oxidase inhibitor phenylisopropylhydrazine, the effects of 5‐hydroxytryptamine injected into the lateral cerebral ventricle were greatly intensified and prolonged; the effects of adrenaline were potentiated to a lesser extent. Those of noradrenaline, dopamine and tryptamine were not intensified and were prolonged to only a slight degree.
PHOSPHORYLPHOSPHATASE AND OXIMES
Authors: EDERT H. , SCHATZBERG‐PORATH G.
Published: July 2012

The effects of pralidoxime iodide, 1,1‐trimethylenebis(4‐formylpyridinium bromide) dioxime and diacetyl monoxime on the activity of phosphorylphosphatase prepared from pig kidney in vitro have been studied. It was found that these oximes, even at high concentrations, did not affect the activity of the enzyme.
INCREASE OF PENTOBARBITONE METABOLISM INDUCED IN RATS PRETREATED WITH SOME CENTRALLY ACTING COMPOUNDS
Authors: KATO R. , CHIESARA E.
Published: July 2012

Rats treated with phenobarbitone, phenaglycodol, glutethimide, nikethamide, meprobamate, chlorbutol and chlorpromazine showed an increased metabolism of pentobarbitone and, at the same time, a diminished sleeping‐time after pentobarbitone. This effect developed 24 hr after treatment, the maximum increase in metabolism occurring after about 48 hr. The increased pentobarbitone metabolism was inhibited by ethionine injected shortly before treatment. Using a liver slice, preparation, increased pentobarbitone metabolism was also observed in vitro. These results are in accord with the view that the capacity of compounds to increase pentobarbitone metabolism may be related to their ability to act directly on microsomal enzyme systems.
RESPONSE OF NORMAL, DENERVATED, AND RESERPINE‐TREATED ARTERIES TO SYMPATHOMIMETIC AMINES AND NICOTINE IN DOGS
Authors: MACMILLAN W. H. , SMITH D. J. , JACOBSON J. H.
Published: July 2012

The sensitivity of normal, denervated carotid arterial segments, and of carotid arteries of dogs previously treated with reserpine, to sympathomimetic amines and nicotine has been compared using isolated perfused segments of these vessels. Arteries from animals and arterial segments treated with reserpine, denervated by peri‐arterial stripping or by re‐anastomosing of segments removed and reversed, both showed an increased sensitivity to noradrenaline which correlated well with a decrease in tissue noradrenaline content. Tyramine did not produce vasoconstriction in denervated vessels, but some constriction was observed when the vessels had been pretreated with noradrenaline or with dopamine or dopa. The effect of nicotine upon dog carotid arterial segments was recorded 130 times. The most frequent response was vasodilatation. This involved both the arterial wall per se and the vasa vasorum. The vasodilatation in response to nicotine was seen in arteries from normal and reserpine‐treated animals and in denervated vessels.
MECHANISM OF CARDIOVASCULAR ACTIONS OF HEPTANOLAMINES
Authors: GARRETT J. , OSSWALD W. , MOREIRA M. GONÇALVES
Published: July 2012

It has been suggested that heptaminol and methylheptaminol should be used as myocardial stimulants because they have cardiotonic actions similar to those of cardiac glycosides. However, as these aliphatic amines show definite sympathomimetic effects, the mechanism of their actions on the heart was investigated, in order to determine whether digitalis‐like properties are involved in these effects. The pattern of pharmacological actions of heptaminol and methylheptaminol was compared with that of catechol amines, tyramine and k‐strophanthin. The influence of atropine, hexamethonium, cocaine and reserpine was also investigated. The results show that both heptanolamines have a long‐lasting cardiostimulant action which is abolished by cocaine and absent in reserpine pretreated animals. The pharmacological activity of these drugs may be entirely attributed to an indirect sympathomimetic action of the tyramine type, probably due to release of endogenous catechol amines. None of the experimental findings is consistent with the alleged digitalis‐like action of these compounds.
AN INVESTIGATION OF THE ACTION OF TYRAMINE AND ITS INTERRELATIONSHIP WITH THE EFFECTS OF OTHER SYMPATHOMIMETIC AMINES
Authors: NASMYTH P. A.
Published: July 2012

Choline 2,6‐xylyl ether potentiated the sympathomimetic effects of tyramine and adrenaline in anaesthetized and spinal cats; the effects of noradrenaline were not significantly affected. The pressor activity of tyramine was also potentiated by the drug in reserpine‐treated spinal cats and in pithed rats. The acute intravenous injection of reserpine in pithed rats potentiated pressor responses to tyramine, but depressed those to adrenaline and noradrenaline. During the intravenous infusion of noradrenaline in spinal cats and pithed rats the pressor responses to tyramine were increased, whilst those to adrenaline and noradrenaline were decreased. Infusion of isoprenaline in a spinal cat depressed responses to tyramine and noradrenaline, but potentiated those to adrenaline. A lower rate of infusion of isoprenaline in the same animal subsequently potentiated adrenaline and noradrenaline, but continued to depress tyramine. These results are held to be inconsistent with the view that the sympathomimetic effects of tyramine are produced entirely by the release of catechol amines.
A GANGLION STIMULATING ACTION OF NEOSTIGMINE
Authors: MASON D. F. J.
Published: July 2012

The actions of neostigmine on transmission in the superior cervical ganglion have been investigated by means of the nictitating membrane preparation in the anaesthetized cat. Intravenous injections of neostigmine produced a rapid and often complete reversal of hexamethonium block, whereas eserine had no effect. This reversal by neostigmine was obtained regularly even after large doses of eserine or dyflos, but was sometimes brief. In ganglia perfused with heparinized plasma containing neostigmine (10−8 to 10−4), there was no potentiation of the responses to maximal stimulation of the preganglionic nerve. Intra‐arterial injections of neostigmine to both normal and preganglronically denervated ganglia produced first a potentiation of the responses to nicotine, then, with larger doses, a contraction of the nictitating membrane and, concurrently, a depression of the responses to nicotine. These results are consistent with the view that neostigmine exerts a direct stimulant action on the ganglion, which is distinct from its anticholinesterase action.
HISTAMINE PROTECTION IN GUINEA‐PIGS PRODUCED BY PLANT TUMOUR EXTRACTS
Authors: BROOME J. , CALLOW R. K. , FELDBERG W. , KOVACS B. A.
Published: July 2012

Stable extracts were obtained from plant tumours, such as Hungarian oak galls and crown galls of infected tomato plants, which, injected intraperitoneally into guinea‐pigs, protected the animals against a subsequent histamine aerosol. The protection produced by the oak gall extracts lasted for a few days and that produced by the crown gall extracts, if injected in sufficient amounts, sometimes for a few weeks.
DEPLETION AND REPLACEMENT OF THE ADRENALINE AND NORADRENALINE CONTENTS OF THE RAT ADRENAL GLAND, FOLLOWING TREATMENT WITH RESERPINE
Authors: CALLINGHAM B. A. , MANN MONICA
Published: July 2012

The effect of reserpine on the adrenaline and noradrenaline contents of rat adrenal glands has been studied. Given subcutaneously to male albino Wistar rats in 3 daily doses of 1 mg/kg, it caused, 24 hr after the final dose, a similar percentage loss of adrenaline and noradrenaline of approximately 50%. Subsequently the adrenaline content slowly increased, until at 14 days from the begining of the experiment there was no significant difference between the reserpine‐treated and the control glands. In contrast, the recovery of the noradrenaline content was rapid, exceeding the control value at 7 days by approximately 250%. This increased content of noradrenaline declined to the normal level by 21 days. The total amine content returned to normal by 7 days and remained at this level subsequently. The effect of re‐depleting the glands of their amine content was investigated. It was found that re‐depletion at 7 days caused a preferential release of noradrenaline, followed at 14 days by a peak of noradrenaline at least as high as that obtained following the initial depletion only. Re‐depletion at 21 days caused an effect similar to that obtained initially. Denervation of the left adrenal gland did not alter the degree of depletion caused by reserpine, nor did it alter the subsequent replacement of the amines as compared with that in the innervated right gland.
CARDIOTONIC ACTION OF TWO TANNINS
Authors: BROADBENT J. L. , BOWDEN K.
Published: July 2012

A tannin isolated from Paullinia pinnata Linn., and tannic acid, have cardiotonic actions on the isolated perfused frog heart. Paullinia tannin is more firmly “fixed” than tannic acid. Tannin solutions contain peroxide, but the cardiotonic action is not dependent on this, since drugs believed to prevent peroxide formation, and sodium pyruvate which destroys peroxides, do not prevent the cardiotonic action. Maximal stimulation by tannin greatly reduces subsequent stimulation by ouabain. If calcium is omitted from the Ringer solution tannins cannot stimulate the heart. In this respect they differ from ouabain. However, the ouabain stimulation can be prevented by prior perfusion with tannin. It is suggested that the antagonism between tannin and ouabain is due to the former preventing ouabain from reaching its receptor sites, and that tannin stimulation is dependent on the formation of a calcium‐tannin complex at the heart surface. In the isolated perfused mammalian heart preparation tannins increase diastolic tonus and coronary flow.
BLOCKING ACTION OF DECAMETHONIUM AT DIFFERENT SITES IN THE AUTONOMIC NERVOUS SYSTEM OF THE CAT
Authors: ABRAHAMS V. C. , HILTON S. M.
Published: July 2012

Doses of decamethonium sufficient to paralyse skeletal and respiratory muscles in the cat for 20 to 30 min can reversibly block transmission at several sites in the autonomic nervous system. The sympathetic vasodilator outflow to skeletal muscle was blocked at the post‐ganglionic nerve endings, probably by preventing the release of acetylcholine. The effects of vagal stimulation on heart‐rate and intestinal contraction were blocked in most experiments, possibly by an action on pre‐ganglionic as well as post‐ganglionic nerve endings. However, decamethonium did not block all cholinergic nerve endings—for example, it did not diminish either the effects of stimulation of the chorda tympani on the submandibular salivary gland or those of pelvic nerve stimulation on the bladder.
ACTIONS OF A MIXTURE OF AMPHETAMINE AND A BARBITURATE IN MAN
Authors: LEGGE D. , STEINBERG HANNAH
Published: July 2012

The effects in man of a mixture of amphetamine and a barbiturate (15 mg of amphetamine sulphate and 300 mg of cyclobarbitone) and of each of the constituents separately were assessed on the performance of simple mental and motor tasks, on the pulse rate and on subjective reports. The mixture produced a pattern of effects which was different from that produced by either drug separately. It impaired the efficiency of the performance of tasks much less than did the barbiturate drug alone; it produced almost as big a rise in the pulse rate as did amphetamine alone; and it produced reports of feeling “elated” from many more subjects than did either drug separately, though there was no corresponding increase in reports of other feelings and sensations.
DETERMINATION OF NEOSTIGMINE AND PYRIDOSTIGMINE IN THE URINE OF PATIENTS WITH MYASTHENIA GRAVIS
Authors: NOWELL P. T. , SCOTT CAROL A. , WILSON A.
Published: July 2012

A method has been described for the estimation of neostigmine and pyridostigmine in urine by ion exchange treatment and colorimetric estimation of the blue complex produced when either of the drugs is made to react with bromophenol blue. Urine containing 2 μg/ml. or more of neostigmine or 3 μg/ml. or more of pyridostigmine can be quantitatively estimated. After intramuscular injection of neostigmine to patients with myasthenia gravis, up to 67% of the drug is excreted, whilst after oral administration less than 5% is excreted. When pyridostigmine is given by mouth, the amount of drug excreted in the urine varies between approximately 2 and 16%. It has been established by chromatographic analysis that the blue complexes formed under these conditions are due only to neostigmine and pyridostigmine respectively and that the quantitative estimation described is a true measure of the amount of these drugs excreted in the urine. The significance of these results is discussed in relation to the absorption and metabolism of the two drugs.