bluuebunny/crossref_metadata_2025 huggingface dataset:
PHARMACOLOGICAL PROPERTIES OF 3‐PHENYL‐5 β DIETHYLAMINOETHYL‐1,2,4‐OXADIAZOLE
Authors: SILVESTRINI B. , POZZATTI C.
Published: July 2012

The general pharmacological properties of Oxolamine (3‐phenyl‐5β‐diethylaminoethyl‐1,2,4‐oxadiazole) are described. The antitussive activity of this drug is more apparent in tests involving a diffuse stimulation of the bronchial tree than with electrical stimulation of the superior laryngeal nerve. These results suggest a predominantly peripheral mechanism of action. Oxolamine also possesses analgesic‐anti‐inflammatory, local anaesthetic and antispasmodic properties. The acute and chronic toxicities of Oxolamine are low, and the experimental results indicate the absence of side effects. The possibility that the antitussive activity is related to the other pharmacological properties is discussed.
EFFECT OF NORADRENALINE, BRETYLIUM AND COCAINE ON THE BLOOD PRESSURE RESPONSE TO TYRAMINE IN THE RAT
Authors: LEŠIĆ R. , VARAGIĆ V.
Published: July 2012

Tyramine is mainly a pressor agent in the rat under urethane, although the hypertensive effect of tyramine in some experiments is followed by a prolonged increase or depression of blood pressure. Bretylium, in doses up to 10 mg/kg, prolonged the response to tyramine, whereas larger doses depressed or blocked its effect. When the hypertensive effect of tyramine was blocked by bretylium, both noradrenaline and dihydroxyphenylalanine, when slowly infused, were found to restore it. The well‐known block by cocaine of the hypertensive response to tyramine could also be reversed by intravenous infusion of noradrenaline and dihydroxyphenylalanine. It is concluded that the infusion of noradrenaline and dihydroxyphenylalanine makes available noradrenaline in the postganglionic adrenergic nerves which is necessary for the action of tyramine.
EFFECT OF COCAINE AND RELATED DRUGS ON THE UPTAKE OF NORADRENALINE BY HEART AND SPLEEN
Authors: MUSCHOLL E.
Published: July 2012

Noradrenaline uptake by heart and spleen after intravenous infusion of noradrenaline was measured in the pithed rat. Cocaine, given before the infusion, inhibited the noradrenaline uptake in relation (a) to the dose administered and (b) to the amount of noradrenaline infused. There was an association between increase in the pressor response to a test dose of noradrenaline and inhibition of the uptake by the heart. Drugs related chemically to cocaine, such as α‐cocaine, amethocaine, and atropine, did not alter the noradrenaline uptake or potentiate the blood pressure response to noradrenaline. The noradrenaline uptake by the heart was unchanged after dibenamine, but blocked by the dichloro‐analogue of isoprenaline. It was concluded that cocaine specifically prevented the uptake of noradrenaline by tissues, thus increasing the amount of noradrenaline available for combination with adrenergic receptors. The dichloro‐analogue of isoprenaline appeared to block both uptake by the heart and the combination with receptors.
THE RESERPINE‐TREATED CAT
Authors: WITHRINGTON P. , ZAIMIS ELEANOR
Published: July 2012

In cats, 24 hr after the administration of 1 mg/kg of reserpine, it was found that (a) the heart is in failure; (b) the sensitivity of the peripheral vessels to adrenaline, noradrenaline and isoprenaline, administered intravenously or close‐arterially, is decreased; (c) any blood pressure changes are, as a rule, secondary to changes in heart contraction; and (d) the peripheral blood flow passively follows the blood pressure changes. Furthermore, any improvement of the circulation at this stage was found to be almost exclusively the result of an amelioration in the force of cardiac contraction.
TISSUE AMINE LEVELS AND SYMPATHETIC BLOCKADE AFTER GUANETHIDINE AND BRETYLIUM
Authors: CASS ROSEMARY , SPRIGGS T. L. B.
Published: July 2012

A single dose of guanethidine produces a substantial, long‐lasting depletion of tissue catecholamines in the rat, whereas a similar dose of bretylium has no effect. Both drugs produce block of the eserine‐induced sympathetic pressor effect. Block by guanethidine is induced more rapidly than is amine depletion. When amine depletion is maximal, a noradrenaline infusion is capable of restoring the response to eserine, but no restoration of the response to eserine occurs after noradrenaline infusion into bretylium‐treated rats. Catecholamine levels in isolated tissues are not reduced when complete block of sympathetic nerve stimulation has been produced by guanethidine. It is suggested that guanethidine possesses a primary bretylium‐like, and a secondary reserpine‐like, blocking action. Guanethidine produces a transient lowering of intestinal 5‐hydroxytryptamine, and this coincides with increased intestinal motility.
EFFECTS OF INJECTION OF MEPESULPHATE INTO THE CEREBRAL VENTRICLES OF CATS
Authors: JOSEPH A. D.
Published: July 2012

The injection of the anticoagulant mepesulphate (Treburon) into the cerebral ventricles of cats resulted in tremor, salivation, tachypnoea, loud calling, and brief periods of various forms of seizures followed by progressive reduction in spontaneous movements and somnolence. The possible sites of action for these effects are discussed.
ACTIONS OF TRIETHYLCHOLINE ON NEUROMUSCULAR TRANSMISSION
Authors: BOWMAN W. C. , RAND M. J.
Published: July 2012

The effects of the triethyl analogue of choline (triethyl 2‐hydroxyethyl ammonium) on muscular activity have been studied in conscious rabbits, chicks, dogs and a cat. The contractions of the tibialis anticus and soleus muscles of cats under chloralose anaesthesia, and of the tibialis anticus muscle of rabbits under urethane anaesthesia and the isolated diaphragm preparation of the rat were also used. In conscious animals, triethylcholine caused a slowly developing muscular weakness which was more severe after exercise and which resembled the symptoms of myasthenia gravis. In nerve‐muscle preparations triethylcholine had a selective action in reducing the contractions of muscles elicited by a high rate of nerve stimulation while leaving unaffected the contractions caused by slower rates of stimulation. During the paralysis of the tibialis muscle of the cat produced by triethylcholine, action potentials recorded from the motor nerve were unaffected and the muscle responded normally to injected acetylcholine and to direct electrical stimulation. The failure of neuromuscular transmission produced by triethylcholine was reversed by injection of choline, but anticholinesterases were ineffective. Choline reduced the toxicity of triethylcholine in mice. It is concluded that triethylcholine produces transmission failure at the neuromuscular junction by interfering with the ability of the nerve endings to synthesize acetylcholine. The possibility that triethylcholine is itself acetylated by the nerve endings and released as an inactive neurohormone is discussed. It was shown that triethylcholine was devoid of depolarizing action and curare‐like blocking action. It possesses a transient ganglion blocking action of the tetraethylammonium‐type as shown in experiments in which it caused a fall in blood pressure and blocked the response of the nictitating membrane to pre‐ but not to post‐ganglionic stimulation of the cervical sympathetic nerve.
ACTION OF SOME DRUGS ON THE DORSAL ROOT POTENTIALS OF THE ISOLATED TOAD SPINAL CORD
Authors: KIRALY J. K. , PHILLIS J. W.
Published: July 2012

A series of drugs which potentiate or antagonize transmission at cholinergic synapses have been tested on the slow depolarizing dorsal root potentials evoked by stimulation of adjacent dorsal and ventral roots. Some drugs acted specifically on the dorsal root potential evoked by ventral root stimulation. Dihydro‐β‐erythroidine, atropine and acetylcholine depressed this potential, whilst anticholinesterase substances in low concentrations potentiated and in higher concentrations depressed it. It is concluded that the results offer some evidence for a cholinergic link in the pathway responsible for the generation of depolarizing potentials in the dorsal root subsequent to ventral root stimulation.
RELATION IN RAT HIND‐LIMB BLOOD VESSELS BETWEEN NERVOUS VASOMOTOR TONE AND THE RESPONSE TO VASOCONSTRICTOR DRUGS
Authors: LAVERTY R.
Published: July 2012

When the nervous component of the vasomotor tone of the blood vessels of the innervated rat hind limb perfused with blood was reduced by ganglion blockade, by section of the nerves to the hind limb, or by the indirect effect of drugs, the vasoconstrictor response of the blood vessels to noradrenaline was immediately increased. This increased peripheral response was observed only when the blood perfusing the hind limb was from the same animal or from a genetically similar animal. Reduction of the nervous component of the vasomotor tone also increased the constrictor response of the hind‐limb blood vessels to adrenaline, ephedrine, tyramine and 5‐hydroxytryptamine, but did not increase the response to angiotensin, vasopressin or S‐methyl isothiourea. Pre‐treatment with reserpine increased the hind‐limb response to noradrenaline but reduced the response to ephedrine, tyramine and 5‐hydroxytryptamine. The results suggest that, in rats, activity in the sympathetic nervous system directly influences the reactivity of peripheral blood vessels to noradrenaline and other sympathomimetic drugs.
EFFECT OF DICHLOROISOPRENALINE ON THE PERIPHERAL VASCULAR RESPONSES TO ADRENALINE IN MAN
Authors: GLOVER W. E. , GREENFIELD A. D. M. , SHANKS R. G.
Published: July 2012

In suitable doses dichloroisoprenaline blocks the initial transient vasodilatation, but leaves unchanged the subsequent vasoconstriction, normally seen during intra‐arterial infusion of adrenaline to the human forearm. Dichloroisoprenaline blocks both the initial transient large vasodilatation, and the subsequent sustained modest vasodilatation, normally seen in the forearm when adrenaline is infused intravenously. Dichloroisoprenaline abolishes the dilator effects of intra‐arterial isoprenaline. These findings are consistent with the hypothesis that the difference between the responses to intra‐arterial and intravenous adrenaline is due to the conversion in the body, elsewhere than in the forearm, of adrenaline to an isoprenaline‐like substance.
ABSORPTION OF FOLIC ACID FROM THE SMALL INTESTINE OF THE RAT
Authors: BURGEN A. S. V. , GOLDBERG N. J.
Published: July 2012

The absorption of folic acid from segments of the small intestine of the rat has been measured in situ with tritium‐labelled folic acid. The fraction absorbed was independent of concentration below 10−6 m but was depressed to half at 4 × 10−5 m. Direct measurements of fluxes showed that the mucosal → serosal flux was about 14 times the serosal → mucosal flux, and therefore that uptake of folic acid is an active process. In the ileum but not in the duodeno‐jejunum, absorption was depressed by the presence of electrolyte. There was little difference in absorptive capacity between jejunum and ileum nor was there any significant change in animals suffering from a dietary deficiency of folic acid.
OCCURRENCE AND SOME PROPERTIES OF ELEDOISIN IN EXTRACTS OF POSTERIOR SALIVARY GLANDS OF ELEDONE
Authors: ANASTASI A. , ERSPAMER V.
Published: July 2012

The posterior salivary glands of Eledone, alone among the tissues of this molluscan species, contain eledoisin, an endecapeptide with activity on blood vessels and extravascular smooth muscles. The salivary glands of Octopus vulgaris and O. macropus lack the polypeptide. Eledoisin is present, in amounts ranging from 20 to 160 μg/g fresh tissue, at all stages of growth and in every season; however, conspicuous differences in the eledoisin content were observed in different groups of animals. Eledoisin is fairly stable in intact salivary glands stored on ice. The most suitable solvent for its extraction is 70 to 80% methanol. Better results are also obtained with boiling diluted acetic acid, than with ethanol, whereas extraction with acetone gives unsatisfactory yields. Eledoisin is stable in neutral or slightly acid medium, but is rapidly destroyed by strong acids and even more rapidly by strong alkalis. It is quickly and completely inactivated by chymotrypsin, and somewhat more slowly and incompletely by trypsin. Carboxypeptidase is ineffective. Passage of crude salivary extracts of Eledone through an alumina column yields preparations of eledoisin which may be considered pure from a biological point of view.
PHARMACOLOGICAL ACTIONS OF ELEDOISIN ON EXTRAVASCULAR SMOOTH MUSCLE
Authors: ERSPAMER V. , ERSPAMER G. FALCONIERI
Published: July 2012

Some general effects and the action of eledoisin on a number of isolated smooth muscle preparations have been studied. It has been found that eledoisin possesses a potent stimulating action on all preparations of gastro‐intestinal smooth muscle examined and also on the bronchial muscle of the guinea‐pig in situ. Preparations of other smooth muscles were less sensitive. The rabbit colon, the guinea‐pig ileum and, subordinately, the rabbit uterus and the frog stomach may be profitably used, owing to their sensitivity and the satisfactory dose/response relationship, for the quantitative bioassay of eledoisin in crude or pure preparations of the polypeptide. In parallel assays eledoisin could be easily distinguished from the biogenic amines and from all other known naturally occurring hypotensive polypeptides (bradykinins, wasp kinin, bradykinin‐like polypeptides of the amphibian skin, physalaemin, substance P). In the unanaesthetized dog, subcutaneous doses of 25 to 100 μg/kg eledoisin caused a powerful stimulation of the motility and some secretions of the alimentary canal. This effect was much less pronounced in the rat and the rabbit.
PHARMACOLOGICAL STUDIES UPON NEURONES OF THE LATERAL GENICULATE NUCLEUS OF THE CAT
Authors: CURTIS D. R. , DAVIS R.
Published: July 2012

Indoles related to 5‐hydroxytryptamine, lysergic acid derivatives, phenethylamine derivatives and some other compounds have been applied electrophoretically to the neurones of the lateral geniculate nucleus of the cat anaesthetized with pentobarbitone sodium. Many of these compounds, particularly 4‐, 5‐ and 7‐hydroxytryptamine and ergometrine, depress the orthodromic excitation of the neurones by volleys in optic nerve fibres, but do not affect antidromic excitation by volleys in the optic radiation or chemical excitation by l‐glutamic acid. It is concluded that the active depressants either block the access of the excitatory transmitter to subsynaptic receptors or prevent the release of the transmitter from optic nerve terminals. The structure‐activity relationships of the depressant substances are discussed.
CHEMICAL STRUCTURE AND PHARMACOLOGICAL ACTIVITY OF SOME DERIVATIVES OF DIGITOXIGENIN AND DIGOXIGENIN
Authors: BROWN B. T. , STAFFORD ANNE , WRIGHT S. E.
Published: July 2012

A series of derivatives of digitoxigenin and digoxigenin were prepared and tested for toxicity in the cat and the guinea‐pig and on the isolated heart of the 48‐hr chick embryo, and for inotropic activity on the cat isolated papillary muscle and the guinea‐pig Langendorff heart. The order of relative potency of the compounds remained the same whether they were tested for toxicity or for positive inotropic activity. There are three molecular centres in the cardiac aglycone that are linked closely with cardiac activity. These are: (a) an OH at carbon‐3 which can be combined as a glycoside, thus enhancing activity, or esterified or oxidized, producing compounds of lower activity; the maximum intensity of the inotropic response was reduced in the less potent compounds; (b) a 14‐β‐OH associated with a cis C‐D ring junction, alteration of which abolished activity; (c) an unsaturated cyclobutenolide ring which cannot be reduced without a great decrease in activity.
PHARMACOLOGY AND CHEMOTHERAPY OF AMPICILLIN—A NEW BROAD‐SPECTRUM PENICILLIN
Authors: ACRED P. , BROWN D. M. , TURNER D. H. , WILSON M. J.
Published: July 2012

The pharmacology and chemotherapy of a new penicillin, 6[d(–)‐α‐aminophenylacetamido] penicillanic acid, are described. It is non‐toxic, is absorbed orally and is distributed throughout the body in a manner similar to other penicillins. It is eliminated unchanged from the body in high concentrations in the bile and urine. Almost all of the antibiotic can be accounted for in the urine and intestinal contents 2 hr after intramuscular administration but not after oral administration. It is concluded that the antibiotic is not metabolized within the body. Studies with infected animals show that it is as effective as the existing oral penicillins against Staphylococcus pyogenes Smith (penicillin sensitive), Streptococcus pyogenes Group A and Diplococcus pneumoniae. It is ineffective against penicillin‐resistant Staphylococci. When tested in mice infected with the gram‐negative organisms, Salmonella typhimurium and Klebsiella pneumoniae, it was considerably more active than tetracycline and chloramphenicol.
ON THE MECHANISM OF TACHYPHYLAXIS TO TYRAMINE IN THE ISOLATED RAT HEART
Authors: AXELROD J. , GORDON EDNA , HERTTING G. , KOPIN I. J. , POTTER L. T.
Published: July 2012

Tyramine was shown to release [3H]‐catecholamines from an isolated rat heart previously perfused with [3H]‐noradrenaline. With successive injections of tyramine the amount of [3H]‐catecholamine released fell progressively and there was a parallel decrease in the increment of amplitude and rate of contraction of the heart. Reserpinized hearts were shown to take up less [3H]‐noradrenaline than normal hearts. Release of radioactivity and loss of responsiveness to tyramine occurred more rapidly in the reserpinized heart. In the same preparation the uptake of [14C]‐tyramine exceeded the quantity of the noradrenaline released.
MECHANISM OF ACTION OF GUANETHIDINE
Authors: KADZIELAWA K.
Published: July 2012

The early hypotensive action of intravenous guanethidine in rabbits, rats and cats anaesthetized with urethane is reversed after pretreatment with iproniazid. The fall in blood pressure following injection of guanethidine in rabbits is reduced after previous administration of reserpine. Reserpine, like adrenalectomy and splenectomy, suppresses the early pressor effect of guanethidine in cats anaesthetized with chloralose. Guanethidine inhibits the action of tyramine and nicotine, but potentiates the effect of noradrenaline on isolated rabbit atria. Guanethidine is also a weak inhibitor of monoamine oxidase activity. The results are discussed and compared with those shown by reserpine. It is concluded that the early effects of guanethidine are mainly due to the release of endogenous catechol amines.
SPIRAMYCIN: A REAPPRAISAL OF ITS ANTIBACTERIAL ACTIVITY
Authors: SUTHERLAND R.
Published: July 2012

Spiramycin was less active than erythromycin in vitro against sensitive strains of Staphylococcus aureus, but was as effective against staphylococcal infections in mice when the drugs were administered immediately after infection: spiramycin was relatively more effective in prophylactic experiments when the antibiotics were administered at 4 or at 6 hr before infection. Strains of staphylococci which had been habituated to either spiramycin or erythromycin in vitro showed complete cross‐resistance to both antibiotics in vitro, but the majority of a number of erythromycin‐resistant strains isolated from patients were sensitive to spiramycin in vitro. Spiramycin was effective against a number of such strains in vivo, but erythromycin had little effect against these infections. Investigation into the distribution of the antibiotics in the serum and tissues of mice showed that spiramycin was maintained in tissues (lung, liver, kidney, spleen and heart) at higher concentrations and for a longer period than erythromycin, although erythromycin was initially present in serum in higher concentrations. It is suggested that the efficacy of spiramycin against experimental infections is due to its persistence in the animal body.
DRUG‐INDUCED CHANGES IN THE CONCENTRATION OF 5‐OR INDOLYL COMPOUNDS IN CEREBROSPINAL FLUID AND CAUDATE NUCLEUS
Authors: ASHCROFT G. W. , SHARMAN D. F.
Published: July 2012

The effects of reserpine and imipramine on the concentration of indolyl compounds bearing an OR group in position 5 (5‐OR indolyl compounds) in the cerebrospinal fluid and the caudate nucleus of the dog have been studied. Reserpine was shown to produce an increase in the concentration of these compounds in the cerebrospinal fluid. In the caudate nucleus reserpine produced a fall in the concentration of the basic 5‐OR indolyl compounds accompanied by an equivalent increase in the concentration of acidic 5‐OR indolyl compounds. No significant change in the concentration of 5‐OR indolyl compounds in the cerebrospinal fluid was observed after treatment with imipramine.
VENTILATORY EFFECTS OF PRETHCAMIDE IN HEALTHY YOUNG MEN
Authors: ANDERTON J. L. , HARRIS E. A.
Published: July 2012

The ventilatory effects of intravenous injections and infusions of prethcamide have been investigated with healthy young adult male volunteers. Ventilatory changes due to the drug were measured at constant inspired PCO2 or constant alveolar PCO2, and in relation to the response to changes in alveolar PCO2. The experiments show that the drug is a mild and somewhat inconstant respiratory stimulant, slow and prolonged in action and liable to give rise to a variety of unpleasant side‐effects.
A COMPARISON OF THE EFFECTS OF SIX BARBITURATES AND A PLACEBO ON INSOMNIA AND MOTILITY IN PSYCHIATRIC PATIENTS
Authors: HINTON J. M.
Published: July 2012

Cyclobarbitone, hexobarbitone, quinalbarbitone sodium, pentobarbitone sodium, phenobarbitone sodium, nealbarbitone and a placebo have been compared in a controlled double‐blind trial in twenty‐four psychiatric patients with insomnia. Each of the barbiturates significantly prolonged sleep and hastened its onset. They also reduced the patients' motility, recorded by an electronic apparatus attached to the bed. There was no clear difference between these barbiturates in onset and duration of action during the 8 hr of recording; some effect upon sleep or motility was present throughout this period. Differences between compounds were of degree rather than of duration of action. Pentobarbitone, quinalbarbitone and phenobarbitone were most effective; cyclobarbitone and hexobarbitone were less effective; nealbarbitone had only a weak hypnotic action.
RATS RESISTANT TO THE DEXTRAN ANAPHYLACTOID REACTION
Authors: HARRIS J. M. , WEST G. B.
Published: July 2012

In one colony of Wistar albino rats 23% were resistant to dextran and to egg‐white, these animals (non‐reactors) failing to show an anaphylactoid reaction after the intraperitoneal or intravenous injection of either of the two substances. Non‐reactors were also found in a few other colonies of Wistar rats but not in colonies of other strains. Procedures which potentiated the anaphylactoid reaction in sensitive rats (reactors) did not alter the response of non‐reactors. Dextran failed to release histamine from the perfused hind‐quarters of non‐reactors although other chemical liberators of histamine were effective. Lack of anaphylactoid reaction was not due to a deficiency of skin histamine or 5‐hydroxytryptamine, and the blood sugar and serum protein levels of non‐reactors were also normal. Non‐reactors could be sensitized to antigens and their serum was antigenic to guinea‐pigs. It is suggested that non‐reactors lack a blood or tissue component with which dextran normally combines to produce an intermediate substance active in releasing amines.
SOME NEUROCHEMICAL ASPECTS OF THE DEPRESSANT ACTION OF γ‐BUTYROLACTONE ON THE CENTRAL NERVOUS SYSTEM
Authors: GIARMAN N. J. , SCHMIDT K. F.
Published: July 2012

γ‐Butyrolactone, a depressant drug of the central nervous system, has been investigated for its ability to alter brain levels of 5‐hydroxytryptamine, γ‐aminobutyric acid and acetylcholine in mice and rats; of these three compounds, only acetylcholine was changed in amount. Levels of acetylcholine in the cerebral cortex were increased by γ‐butyrolactone with a time‐course which closely followed the depressed state of the animal. Indirect evidence has been presented to show that in the mid‐brain and brain stem the change in acetylcholine level induced by γ‐butyrolactone is sharply localized in an area of the mesencephalon that contains the corpora quadrigemina.
A COMPARISON OF THE BIOLOGICAL ACTIVITIES OF FOUR PROSTAGLANDINS
Authors: HORTON E. W. , MAIN I. H. M.
Published: July 2012

The biological activities of prostaglandins E1, E2, E3 and F1α have been compared. Prostaglandins E1, E2 and E3 were qualitatively similar; E1 and E2 were about equiactive, but E3 was less active on all preparations. Prostaglandin F1α was a less potent vasodilator than E1 on the cat gastrocnemius muscle blood flow and skin blood flow and a less potent depressor drug on rabbit blood pressure. On the rabbit isolated jejunum F1α was twice as active as E1 but on the guinea‐pig isolated ileum E1 was about forty times more active than F1α. One qualitative difference between these prostaglandins was observed; on the rabbit fallopian tube in vivo prostaglandins of the E series decreased both the tone and the peristalsis of the tube whereas prostaglandin F1α increased tubal tone.
ANTI‐EMETIC ACTIVITY OF PHENOTHIAZINES IN RELATION TO THEIR CHEMICAL STRUCTURE
Authors: BHARGAVA K. P. , CHANDRA OM
Published: July 2012

Twelve phenothiazine derivatives have been studied for anti‐emetic potency in dogs against emesis induced by apomorphine. The PD50S of all the compounds were determined and the activities compared with chlorpromazine hydrochloride as standard. Thioproperazine methanesulphonate was 300 times more active than chlorpromazine hydrochloride and twice as active as perphenazine sodium citrate. The anti‐emetic activity of the compounds has been correlated with their chemical structure.
THE EFFECT OF CERTAIN ETHYLENEIMINES ON RENAL FUNCTION
Authors: JACKSON H. , JAMES R. M. V.
Published: July 2012

Certain simple derivatives of ethyleneimine cause an intense and prolonged diuresis in nonhydrated rats. Sodium, potassium and chloride excretion is unaffected by these compounds. Ethyleneimine also causes a diuresis in the rat, but the poly‐functional compound thiotepa is ineffective. The relationship between structure and activity of a number of compounds is discussed with particular reference to the possibility that the diuresis is due to the in vivo liberation of ethyleneimine.
A QUANTITATIVE STUDY OF THE EFFECT OF COCAINE ON THE RESPONSE OF THE CAT NICTITATING MEMBRANE TO NERVE STIMULATION AND TO INJECTED NORADRENALINE
Authors: HAEFELY W. , HÜRLIMANN A. , THOENEN H.
Published: July 2012

Results are reported of a quantitative study of the potentiating effect of cocaine on the responses of the cat nictitating membrane to intravenously and intra‐arterially injected noradrenaline, as well as to different types of sympathetic nerve stimulation. Responses of the membrane to noradrenaline were potentiated more with intravenous than with close‐arterial injections. From studies of the responses of the nictitating membrane to various forms of sympathetic nerve stimulation before and after injection of cocaine, conclusions are drawn as to the extent to which the transmitter amine liberated by nerve activity is normally removed and its effect thereby limited in duration and extent. This uptake was greatest at low stimulus frequencies. The mechanism by which cocaine potentiates sympathetic responses is discussed.
EFFECT OF HEXADIMETHRINE BROMIDE ON PLASMA KININ FORMATION, HYDROLYSIS OF p‐TOSYL‐L‐ARGININE METHYL ESTER AND FIBRINOLYSIS
Authors: EISEN V.
Published: July 2012

The antiheparin agent hexadimethrine bromide, in concentrations of 20 to 200 μg/ml., inhibited the activation by active Hageman factor of the plasma enzyme which releases kinin from substrate. Once activated, this kinin‐forming enzyme was not consistently inhibited by hexadimethrine in a concentration of 1 mg/ml. Surfaces which induce kinin formation by activating Hageman factor in plasma (glass, kaolin, celite, barium carbonate and carboxymethylcellulose) were inactivated by bathing in aqueous solutions of hexadimethrine. The effects of hexadimethrine on Hageman factor and on glass were not abolished by amounts of heparin which neutralize most other actions of hexadimethrine. Hexadimethrine prevented the activation by kaolin, but not by streptokinase, of p‐tosyl‐l‐arginine methyl ester‐splitting and fibrinolytic factors in plasma; once these enzymes were activated by kaolin, they could not be inhibited by hexadimethrine. Hexadimethrine, given locally or intravenously into guinea‐pigs, reduced the increase in capillary permeability produced by intracutaneous injections of kaolin suspensions.
INNERVATION OF THE LARGE INTESTINE OF THE TOAD (BUFO MARINUS)
Authors: BOYD HELEN , BURNSTOCK G. , ROGERS D.
Published: July 2012

The morphology, physiology and pharmacology of the innervation of the toad (Bufo marinus) large intestine have been studied. The large intestine can be divided into the regions colon, rectum and cloaca, on morphological grounds, but acts as a unit in response to nerve stimulation. Of the right and left nerves, each appears to supply the entire large intestine. Autonomic innervation of the large intestine of Bufo marinus is as follows: (1) The 9th and 10th spinal nerves (pelvic) contain predominantly excitatory preganglionic cholinergic fibres, but some inhibitory adrenergic fibres are also present in most preparations. (2) The splanchnic nerves contain inhibitory postganglionic adrenergic fibres from the 3rd to 5th sympathetic ganglia, and a small number of excitatory cholinergic fibres. The pathway of adrenergic inhibitory fibres to the large intestine alongside the posterior mesenteric artery as seen in mammals is rarely present in the toad. Several nonspecific actions of autonomic drugs on the large intestine are discussed. The functional organization of the autonomic innervation of the toad large intestine is similar to that in mammals, that is the large intestine is controlled by antagonistic cholinergic and adrenergic nerves. However, the separation of these two types of nerve fibres into anatomically distinct nerves does not appear to be as complete as in mammals. It is suggested that inhibitory autonomic control of the alimentary canal in vertebrates first appears in the hind‐gut region.
THE EXCITATION AND DEPRESSION OF MAMMALIAN CORTICAL NEURONES BY AMINO ACIDS
Authors: CRAWFORD J. M. , CURTIS D. R.
Published: July 2012

Amino acids related to L‐glutamic and γ‐amino‐n‐butyric acid have been administered electrophoretically, and by pressure ejection, into the extraneuronal environment of single neurones in the pericruciate cortex of cats anaesthetized with allobarbitone or allobarbitone‐urethane. Acidic amino acids related to glutamic acid, particularly N‐methyl‐D‐aspartic acid, excited cortical neurones. Neutral amino acids related to γ‐amino‐n‐butyric acid, particularly 3‐amino‐l‐propanesulphonic acid, depressed cortical neurones. Some of the depressants blocked the antidromic invasion of Betz cells by pyramidal volleys. There are no essential differences between the sensitivities of cortical and spinal neurones towards locally administered amino acids. A transmitter function of such amino acids within the mammalian central nervous system is considered unlikely.
PRODUCTION OF HERITABLE PARTIAL STERILITY IN THE MOUSE BY METHYL METHANESULPHONATE
Authors: JACKSON H. , PARTINGTON M. , WALPOLE A. L.
Published: July 2012

Partial sterility, in the sense of reduced reproductive capacity, has been demonstrated in the F1 progeny of male mice mated in the second week after a single dose of methyl methanesulphonate (50 mg/kg, intraperitoneally) with females of proved fertility. Sterility, both partial and complete, was encountered in the F2 generation obtained by mating F1 males and females with fertile partners. These results show that the compound, in a substerilizing dose, is capable of producing transmissible genetic damage. It is suggested that the procedure used is a practicable method of testing drugs for possible genetic effects.
URINARY EXCRETION OF CATECHOL AMINES IN THE RAT AFTER THEIR LIBERATION BY RESERPINE OR DEXAMPHETAMINE
Authors: BISCARDI A. M. , CARPI A. , ORSINGHER O. A.
Published: July 2012

Daily urinary excretion of catechol amines in normal rats and in rats from which the adrenal medullae had been removed has been determined by a photofluorimetric method. In both groups, reserpine (2 mg/kg, intraperitoneally) produces: (1) A decrease in the urinary excretion of noradrenaline which persists for more than 3 weeks; this action is not influenced by monoamine oxidase inhibitors and mecamylamine. (2) An increase, within 20 to 68 hr, in the urinary excretion of adrenaline, even though the urine of rats without adrenal medullae does not usually contain adrenaline. These effects are prevented by monoamine oxidase inhibitors and, in the normal animals, are reduced by mecamylamine. In both groups, dexamphetamine (6 mg/kg, intraperitoneally) produces an increase in the excretion of adrenaline and noradrenaline, the adrenaline appearing in the urine of the rats without adrenal medullae within 20 to 44 hr. Mecamylamine prevents the effect of dexamphetamine on the excretion of noradrenaline. Dexamphetamine, administered within a week of reserpine treatment, produces its usual effects on the urinary excretion of catechol amines in normal rats, but has no effect in rats without adrenal medullae. The results are discussed with regard to both the mechanism by which reserpine and dexamphetamine influence the peripheral stores of adrenaline and noradrenaline, and the significance of the adrenal and extra‐adrenal chromaffin system.
THE INHIBITORY ACTIONS OF PROSTAGLANDINS ON RESPIRATORY SMOOTH MUSCLE
Authors: MAIN I. H. M.
Published: July 2012

Prostaglandin E1, in concentrations as low as 1 ng/ml., relaxed isolated tracheal muscle from cat, monkey, rabbit, guinea‐pig and ferret. Tracheal muscle from the cat, monkey and rabbit did not exhibit inherent tone and the effect of prostaglandin E1 on these preparations was seen only after a sustained contraction had been produced by a previous dose of acetylcholine or of another agonist. Prostaglandins E2, E3 and F1α also relaxed isolated cat tracheal muscle which had been stimulated by acetylcholine: their activities relative to that of prostaglandin E1 were, respectively, 1.0, 0.2 and 0.002. In the anaesthetized cat prostaglandin E1 increased lung “resistance to inflation” (presumably comparable to bronchial resistance) and the heart rate. In the anaesthetized rabbit and guinea‐pig, prostaglandin E1 antagonized the rise in resistance to inflation of the lungs obtained after vagal stimulation or after the intravenous injection of histamine; it sometimes lowered the resistance to inflation in these species. The possibility that prostaglandin may have a local physiological role in the control of bronchial smooth muscle tone is discussed.
THE USE OF CHANGES IN CAPILLARY PERMEABILITY IN MICE TO DISTINGUISH BETWEEN NARCOTIC AND NONNARCOTIC ANALGESICS
Authors: WHITTLE B. A.
Published: July 2012

An extension of the “ squirming test” is described which makes the method specific for nonnarcotic analgesics. The intraperitoneal injection of acetic acid causes squirming and an increase in capillary permeability that is measured by direct estimation of plasma‐bound dye (Pontamine Sky Blue) which has leaked into the peritoneal cavity. Nonnarcotic analgesics inhibit squirming and leakage of dye. Values for the oral ED50s for both effects are given for a number of typical compounds. Narcotic analgesics, in doses that produce analgesia, inhibit squirming but do not significantly affect leakage of dye. Drugs that stimulate the central nervous system and also inhibit squirming have no significant effect on leakage of dye over the range of doses which inhibit squirming. Corticosteroids do not significantly inhibit either squirming or leakage of dye.
THE DISTRIBUTION OF PARENTERAL IRON HAEMATINICS IN NONPREGNANT, PREGNANT AND LACTATING RATS
Authors: HÖGBERG K.‐G. , LINDVALL S.
Published: July 2012

The distribution of 59Fe has been investigated in nonpregnant, pregnant and lactating rats and their young after injection of solutions containing a high molecular weight iron‐dextrin complex (iron‐dextrin, intravenously), and a low molecular weight complex of iron, sorbitol and citric acid (iron‐sorbitol, intramuscularly), each labelled with 59Fe. At different times after injection of a dose corresponding to 1.5 mg of iron per kg of body weight, the quantity of 59Fe was determined in different organs, urine and carcass, and for pregnant rats also in foetuses and placentas. In some investigations, distribution in the foetuses was also studied. Iron‐dextrin was localized mostly in the livers of both pregnant and nonpregnant rats; 59Fe was then redistributed from this organ and incorporated into the erythrocytes. In pregnant rats, redistribution was accompanied by a placental transfer, the degree of incorporation into the erythrocytes of the mother being diminished. About 30% of the iron‐sorbitol was excreted in the urine, while the remainder was distributed throughout the whole organism. Incorporation into the erythrocytes and placental transfer began earlier with iron‐sorbitol than with iron‐dextrin. At 14 days from injection into nonpregnant rats, however, the degree of incorporation into the erythrocytes of iron from the two complexes was identical. The rate at which incorporation of 59Fe occurred into the erythrocytes was the same for the two preparations. The degree of incorporation into the erythrocytes after injection of iron‐sorbitol into pregnant rats diminished in the same pattern as for iron‐dextrin. Investigations into the mechanism of the placental transfer of iron‐sorbitol from mother to foetus suggested that this is essentially an active process.
THE EFFECTS OF ANTIMONY UPTAKE ON THE LOCATION AND PAIRING OF SCHISTOSOMA MANSONI
Authors: KHAYYAL M. T.
Published: July 2012

The rate of uptake and elimination of antimony by both male and female schistosomes has been measured. It has been confirmed that the female schistosome is more susceptible to antimony therapy than the male since she absorbs more drug. The changes in location of the worms and the separation of the sexes following one or more injections of antimony potassium tartrate have been related to the different rates of uptake and elimination of the drug by the two sexes. The suppressive treatment of schistosomiasis is discussed in the light of these observations.
Action of various sympathomimetic amines on the isolated stripped vas deferens of the guinea‐pig
Authors: NEDERGAARD O. A. , WESTERMANN E.
Published: July 2012

. The contractile potencies of some sympathomimetic amines and cholinergic drugs were studied in the isolated, stripped vas deferens of the guinea‐pig.

. α‐Methylnoradrenaline, adrenaline and metaraminol produced the same relative maximal responses as noradrenaline, which served as reference drug; on the other hand, octopamine, dopamine and α‐methyldopamine were much less active. Short term pretreatment of the animals with reserpine did not affect the maximal relative responses.

. Tyramine, α‐methyl‐m‐tyramine and hordenine methiodide had little effect on the untreated preparation. In the presence of just threshold concentrations of noradrenaline, the relative maximal responses to tyramine and hordenine methiodide were markedly increased.

. The relative maximal response to carbachol was the same as that to noradrenaline, while that to DMPP was smaller. In contrast to carbachol, the action of DMPP was potentiated by pretreatment of the preparation with noradrenaline.
The mobilization of free fatty acids from rabbit adipose tissue in situ
Authors: LEWIS G. P. , MATTHEWS J.
Published: July 2012

. The epigastric adipose tissue of rabbits has been prepared so that the effects of close arterial injections and infusions on blood flow and release of free fatty acids (FFA) can be studied. The effects of pharmacologically active agents and hormone preparations have been investigated.

. Release of FFA was stimulated by synthetic adrenocorticotrophic hormone (ACTH), α and β melanophore stimulating hormone (MSH), porcine growth hormone, glucagon, thyrotropic hormone (TSH) and luteotropic hormone (LTH). Single injections of fat‐mobilizing agents produce a sustained rise in the release of FFA.

. Although pitressin caused release of FFA, synthetic vasopressin and oxytocin failed to do so. The FFA releasing activity of pitressin has therefore been attributed to a contaminant.

. Catecholamines were found not to stimulate release of FFA from this fat depot, but were found to increase plasma FFA when infused intravenously.

. Injections of acetylcholine, histamine, bradykinin, 5‐hydroxytryptamine, synthetic arginine vasopressin, and lysine vasopressin, oxytocin, angiotensin and FSH did not stimulate release of FFA although marked effects on blood flow were produced.

. Injections of prostaglandin E1 gave sustained increases in blood flow, and inhibited FFA release when stimulated by growth hormone.

. The mobilization of FFA is sometimes associated with an increased rate of blood flow.
Effect of rabbit antibodies against angiotensin‐II on the pressor response to angiotensin‐II and renal hypertension in the rat
Authors: HEDWALL P. R.
Published: July 2012

. In the intact or nephrectomized rat, the pressor responses to synthetic angiotensin‐II‐amide, beta‐angiotensin‐II and native “rat angiotensin” could be inhibited by intravenous injection of rabbit serum containing antibodies against synthetic angiotensin‐II‐amide.

. The pressor responses to vasopressin or noradrenaline were not influenced by anti‐angiotensin serum.

. A single injection of anti‐angiotensin serum inhibited the pressor responses to angiotensin‐II‐amide for a period of 2.5 hr.

. Intravenous infusion or daily intraperitoneal injection of anti‐angiotensin serum did not influence blood pressure levels in renal hypertensive rats.
The inhibitory action of noradrenaline and adrenaline on acetylcholine output by guinea‐pig ileum longitudinal muscle strip
Authors: PATON W. D. M. , VIZI E. S.
Published: July 2012

Noradrenaline and adrenaline reduce the output of acetylcholine by the guinea‐pig ileum longitudinal strip by up to 80%, both in resting conditions and after stimulation. The effect is graded with dose, and is detectable with noradrenaline 2 × 10−7 g/ml. Adrenaline is approximately 4 times as active as noradrenaline, and its action after being washed out is more persistent.

If resting output is high, both amines have a proportionately greater effect and their action, as dosage is increased, is to reduce resting output to a basal level, relatively constant from strip to strip, of about 10 ng/g/min.

With stimulation, the effect of the amine is greater at low frequencies, when the output per volley is high, than at high frequencies. The effect is reduced by increasing the number of shocks delivered. There thus appears to be a basal output per volley, of the order of 1–2 ng/g/volley, which can be reached either by relatively rapid stimulation, by prolonged stimulation, or by treatment with these amines.

If noradrenaline is applied during continued stimulation at 40/min, the depression of acetylcholine output during its presence is followed by an augmented output when the drug is withdrawn. The magnitude of this “overshoot” increases with the duration of noradrenaline exposure.

Phenylephrine 4 μg/ml. and amphetamine 20 μg/ml. reduced the acetylcholine output, but isoprenaline 1 μg/ml., dopamine 1 μg/ml. and methoxamine 10 μg/ml. were ineffective.

Phenoxybenzamine reduced the resting output and increased the stimulation output. Of the two other blocking agents examined, phentolamine had no effect on either resting or stimulation output and ergotamine transiently reduced stimulation output. The effect of phenoxybenzamine was not due to a reaction with either adrenoceptive or muscarinic receptors.

Phenoxybenzamine, phentolamine and ergotamine abolished the effect of adrenaline and noradrenaline on both resting output and on output in response to stimulation.

In strips obtained from animals treated with reserpine and guanethidine, a rise in resting acetylcholine output and in stimulation output at low frequencies was found. In these conditions, noradrenaline was still effective.

Reducing the hydroxytryptamine content of the strips by treatment with p‐chloro‐(±)‐phenylalanine did not significantly affect acetylcholine output.

It is concluded that acetylcholine output by the nervous networks of the longitudinal strip is under the normal control of the sympathetic by a species of presynaptic inhibition mediated by α receptors. This implies that for a tissue under dual autonomic control, withdrawal of sympathetic control will lead to a parasympathetic response which is not only unopposed but also itself enhanced.
Spontaneous and evoked release of neurotransmitter substances in the longitudinal muscle of the anterior mesenteric artery of the domestic fowl
Authors: BOLTON T. B.
Published: July 2012

Changes in length of the longitudinal muscle of the anterior mesenteric artery of the domestic fowl (LMAMA) were recorded isotonically.

The actions of physostigmine and hyoscine suggest that the tone of the LMAMA is dependent on a resting release of acetylcholine within the tissue.

Catecholamines inhibited the contractions obtained in response to stimulation of cholinergic nerves; this was a β‐receptor effect. After β‐receptor blockade, noradrenaline, but not isoprenaline, weakly facilitated the effects of stimulating cholinergic nerves.

In the presence of hyoscine, nicotine relaxed preparations of the LMAMA in which the tone had been raised with barium chloride. These relaxations were considered to be due to a release of catecholamine probably from sympathetic nerves.
The cardio‐toxicity of isoprenaline during hypoxia
Authors: COLLINS J. M. , McDEVITT D. G. , SHANKS R. G. , SWANTON J. G.
Published: July 2012

The effects of the intravenous injection of isoprenaline on heart rate and arterial pressure has been studied in dogs artificially respired with room air or with 12% oxygen—88% nitrogen.

In dogs breathing room air, isoprenaline in doses from 0.02 to 500 μg/kg increased heart rate and reduced arterial pressure. Ventricular fibrillation was produced in one out of three dogs given 250 μg/kg. This was the only dog breathing room air which was killed by isoprenaline.

In dogs breathing room air the repeated intravenous injection at 5‐min intervals of 2.5 μg/kg increased heart rate and reduced arterial pressure. No ill effects were produced by six doses.

In dogs respired with 12% oxygen—88% nitrogen the Pao2 was reduced from 84 to 38 mm Hg with no changes in Paco2. In these dogs death was produced by doses of isoprenaline which in dogs breathing room air produced normal responses.

The fatal dose of isoprenaline (10–50 μg/kg) reduced heart rate and arterial and pulse pressures; sinus rhythm persisted until arterial pressure was less than 50 mm Hg. Ventricular fibrillation did not occur; death occurred from cardiac asystole.

Death was produced in a similar way in dogs with hypoxaemia by giving four or five doses of isoprenaline (2.5 μg/kg) at 5‐min intervals or by two doses of 25 μg/kg.

The final reduction in arterial pressure during a fatal response resulted from a reduction in cardiac contractility.

These lethal effects of isoprenaline could be prevented by pretreatment with propranolol.