bluuebunny/crossref_metadata_2025 huggingface dataset:
DRUG‐INDUCED CHANGES IN BRAIN ACETYLCHOLINE
Authors: GIARMAN N. J. , PEPEU G.
Published: July 2012

In rats, drug‐induced depression of the central nervous system has been shown generally to be associated with an elevation in level of total acetylcholine in the brain. This generalization held true for a wide variety of depressant drugs with one notable exception: the subacute administration of reserpine, with which there was an increase in cerebral acetylcholine after the first dose, but a return to normal levels after subsequent doses, despite continued depression of the animals. Reduction in the level of total acetylcholine in the brain followed the administration of certain convulsants (pentylenetetrazole and 3,5‐dimethylbutylethylbarbiturate); but no change was seen after the administration of several mildly exciting agents. The notable exceptions to this generalization were atropine and scopolamine, which significantly lowered brain acetylcholine in doses producing mild excitation in only some of the animals and no gross manifestations in the rest.
HYPERPYREXIA AS A CONTRIBUTORY FACTOR IN THE TOXICITY OF AMPHETAMINE TO AGGREGATED MICE
Authors: ASKEW BERYL M.
Published: July 2012

A rise of body temperature into a range lethal to mice preceded death in groups of mice injected with amphetamine sulphate. At dose levels from 8.8 to 66.7 mg/kg, mortality was associated with the extent of rise in body temperature of the mice, irrespective of the actual dose administered. Isolated mice given comparable doses of amphetamine also showed a marked increase in body temperature. However, except in a very few cases, it did not rise into the range found to be lethal. Amphetamine was more toxic to isolated mice subjected to foot‐shock than to isolated mice housed under normal conditions. This has also been shown to be related to the extent of rise in body temperature of the mice. The effect of a number of substances on grouped amphetamine toxicity was investigated. Chlorpromazine and phenoxybenzamine partially antagonized the sharp rise in temperature following the administration of amphetamine, and also significantly reduced mortality. Calcium acetylsalicylate was without effect on the rise of body temperature or on mortality. Both the hypothermic compound 4‐methyl‐5‐(β‐chlorethyl)‐thiazole (S.C.T.Z.) and l‐thyroxine sodium potentiated the rise in temperature and caused a significant increase in mortality.
ORIGIN OF THE CHOLINERGIC RESPONSE OF THE RABBIT INTESTINE TO STIMULATION OF ITS EXTRINSIC SYMPATHETIC NERVES AFTER EXPOSURE TO SYMPATHETIC BLOCKING AGENTS
Authors: BOYD G. , GILLESPIE J. S. , MACKENNA B. R.
Published: July 2012

The effect of guanethidine and of bretylium on the response to nerve stimulation has been studied on two types of isolated innervated preparations of rabbit intestine. One preparation was that of the rabbit ileum in which the periarterial (mainly sympathetic) nerves were stimulated: the other was the doubly innervated rabbit colon where either parasympathetic (pelvic) or sympathetic (lumbar colonic) nerves were stimulated. In both preparations guanethidine and bretylium in appropriate dosage specifically blocked the inhibitory effect of sympathetic nerve stimulation while leaving the response to parasympathetic nerve stimulation and to acetylcholine unaltered: the response to noradrenaline was unaltered or potentiated. In the ileum, after the addition of guanethidine or of bretylium, the inhibitory response to periarterial nerve stimulation was replaced in every preparation by a motor response which had the same frequency sensitivity as parasympathetic nerves. In the colon a motor response to sympathetic nerve stimulation was rarely obtained after blocking the inhibitory response. When such a motor response was uncovered it had similar characteristics to the motor response in the ileum. Furthermore, if the parasympathetic nerves were stimulated for prolonged periods both the parasympathetic and sympathetic motor responses were reduced. These results do not support the idea that post‐ganglionic sympathetic nerves to the intestine are generally cholinergic and are themselves responsible for the motor responses. The experimental results are more conveniently explained by assuming a mixture of cholinergic and adrenergic fibres in the nerves stimulated.
A METHOD FOR THE QUANTITATIVE ESTIMATION OF DRUGS ON THE ISOLATED INTACT TRACHEA
Authors: JAMIESON DANA
Published: July 2012

A method is described for the detection and comparison of substances active on tracheal smooth muscle. Several pharmacological agents affecting smooth muscle have been tested using the technique. Sensitivity was high, results reproducible and linear log dose‐response relationships obtained over a wide dosage range. The method has been used to estimate the concentrations of adrenaline, acetylcholine and histamine in test solutions of these compounds.
STIMULATION AND SENSITIZATION OF THE ISOLATED VENUS HEART BY CEREBROSPINAL FLUID
Authors: BOWERS M. B.
Published: July 2012

5‐Hydroxytryptamine was not detected in animal cerebrospinal fluid after amine oxidase inhibitors, reserpine, or both. Both human and animal cerebrospinal fluid can produce a stimulating effect on the clam heart which is not due to 5‐hydroxytryptamine. Cerebrospinal fluid also has the property of increasing the sensitivity of the clam heart to 5‐hydroxytryptamine.
PROTEUS VULGARIS URINARY TRACT INFECTIONS IN RATS; TREATMENT WITH NITROFURAN DERIVATIVES
Authors: HOSSACK D. J. N.
Published: July 2012

Ascending urinary tract infections with stone formation have been produced experimentally in rats, using a modification of the method of Vermuelen & Goetz (1954a, b). A zinc disc infected with a culture of Proteus vulgaris was inserted into the bladder by suprapubic cystotomy under ether anaesthesia. The pH of the urine rises from 6.9 to 8 or 9 and calculi develop in the bladder within a few days of infection. The bladder and ureters become swollen, distended and inflamed, and renal abscesses develop. Death from renal failure generally occurs within 10 days of infection. Oral treatment with nitrofurantoin was commenced three days after infection and continued for one month. This arrested the initial rise in urine alkalinity and stone formation, and few, if any, macroscopic lesions were found at post‐mortem examination. Of nine nitrofuran derivatives examined for activity against this infection several showed slight activity, but only one, N‐(5‐Nitrofurfurylidene)‐γ‐butyric acid, was as active as nitrofurantoin when given at four times the dose, but it was also one‐third as toxic. It is concluded that this technique is suitable for the examination of potential urinary antiseptics.
WOUND HEALING IN RATS WITH THE ANTIBIOTIC FUCIDIN
Authors: CALNAN J. , FRY H. J. H.
Published: July 2012

Fucidin, a new antibiotic which is stated to improve wound healing, was fed to rats subjected to incised wounds on the back. There was a significant difference (at the 1% level) in tensile strength of five‐ and seven‐day wounds, but none between Fucidin‐treated rats and their controls.
NEUROMUSCULAR BLOCKING PROPERTIES OF SOME BISTROPINIUM ESTERS
Authors: HAINING C. G. , JOHNSTON R. G.
Published: July 2012

The neuromuscular blocking, anti‐acetylcholine and ganglion blocking properties of two series of bistropinium esters were examined. The neuromuscular blocking activities of the mandelic acid esters of NN′‐polymethylenebis(tropinium halides) were found to depend upon the number of carbon atoms (n) in the linking chain. Potency was enhanced more than 50 times as n was increased from 2 to 7. Compounds in which n equalled 7, 8, 9, 10 and 12 differed little in activity, but were generally more potent than tubocurarine in cats and rabbits. A peak of ganglion blocking action was obtained at the pentamethylene member. Esterification enhanced the feeble neuromuscular blocking properties of NN′‐decamethylenebis(tropinium halide), the mandelic acid ester being more effective than the tropic, benzoic or phenylacetic acid esters in cats and rabbits. When two benzoic or mandelic acid esters of tropine were linked through their nitrogen atoms by a phenylenedimethyl grouping (‐CH2.C6H4.CH2‐), meta substitution was more effective than was ortho or para in producing neuromuscular block. The effectiveness of esterifying acids in m‐phenylenedimethyl derivatives decreased in the following order, phenylacetic> tropic or mandelic>benzoic>acetic and diphenylacetic.
SOME PHARMACOLOGICAL PROPERTIES OF BRAIN GANGLIOSIDE
Authors: BOGOCH S. , PAASONEN M. K. , TRENDELENBURG U.
Published: July 2012

The effects of a preparation of purified brain ganglioside and of neuraminic acid have been studied on various pharmacological test preparations. In concentrations of 10 μg/ml. or more, ganglioside stimulates the isolated guinea‐pig ileum; graded responses are usually obtained. Various substances, known to antagonize the actions of other stimulant substances, fail to affect the response to ganglioside. Ganglioside and neuraminic acid neither stimulate the superior cervical ganglion of the cat nor do they affect ganglionic transmission. Ganglioside and neuraminic acid did not change the response of the frog rectus abdominis muscle to acetylcholine, nor did they affect the blood pressure of the cat. Ganglioside (2 μg/ml. or more) stimulates the isolated heart of Venus mercenaria, but the response, which develops slowly, decreases with repeated administration of ganglioside. The response is not blocked by 2‐bromo‐lysergic acid diethylamide and there is no indication that it is due to the liberation of endogenous 5‐hydroxytryptamine or related indole compounds. For both the heart of Venus mercenaria and guinea‐pig ileum, the activity demonstrated by brain ganglioside is specifically a property of the whole molecule, since neither neuraminic acid itself nor a preparation of brain ganglioside from which only two‐thirds of its neuraminic acid had been removed are active.
A STUDY OF POSSIBLE MEDIATORS OF INFLAMMATORY REACTIONS IN THE MOUSE FOOT
Authors: NORTHOVER B. J. , SUBRAMANIAN G.
Published: July 2012

A number of compounds have been studied for their ability to antagonize the inflammatory reaction produced by injections of formaldehyde and 5‐hydroxytryptamine in the mouse foot. An attempt has been made to elucidate the ways in which certain hydroxybenzoates, pyrazolones, sympathomimetic amines, flavone and flavanone glycosides, local anaesthetics, antihistamines and anti‐5‐hydroxytryptamine substances produce their anti‐inflammatory effect.
STIMULATION OF INTESTINAL NERVOUS ELEMENTS BY ANGIOTENSIN
Authors: ROBERTSON P. A. , RUBIN DANA
Published: July 2012

The stimulation of nervous elements in the intestine by the polypeptide angiotensin has been examined. Comparisons between nicotine, a neurotropic agent, acetylcholine which exerts principally a musculotropic action and angiotensin have been made by examining their interactions with hexamethonium and the anticholinesterase 1,5‐di‐(p‐N‐allyl‐N‐methylaminophenyl)pentan‐3‐one dibromide in both the rabbit and guinea‐pig ileum. The effect of atropine on the responses of the guinea‐pig ileum and botulinum toxin on the responses of the rabbit ileum to angiotensin was also tested. The results show that angiotensin causes most of its contractile response in both the guinea‐pig and rabbit ileum by an indirect action, through the stimulation of nervous tissue.
MEASUREMENT OF UTERINE ACTIVITY IN VITRO BY INTEGRATING MUSCLE TENSION
Authors: STYLES P. R. , SULLIVAN T. J.
Published: July 2012

Spontaneous or electrically stimulated activity of the uterus is measured isometrically in vitro by integrating tension against time. Uterine contractions move the operating rod of a potentiometer transducer, the output voltage from which is coupled to an electrical integrator motor and a servo recorder. Several parameters of uterine activity can be expressed in a single measurement, and a record of isometric contractions is obtained simultaneously. Oxytocin can be assayed accurately and the effect of drugs on uterine motility can be measured.
EFFECT OF ETHAMIVAN (VANILLIC ACID DIETHYLAMIDE) ON THE RESPIRATORY RESPONSE OF HEALTHY YOUNG MEN TO CARBON DIOXIDE, IN THE ABSENCE OF HYPOXIA
Authors: ANDERTON J. L. , COWIE J. F. , HARRIS E. A. , SLEET R. A.
Published: July 2012

The effect of ethamivan (vanillic acid diethylamide) on the ventilatory response to carbon dioxide has been investigated in healthy young adult males. Intravenous infusion of the drug at a rate of 9 mg/min causes respiratory stimulation depending in degree upon the prevailing alveolar CO2 tension. When the latter is low stimulation by the drug is most marked and may largely support respiration below the CO2 threshold. As alveolar Pco2 increases, the effect of the drug disappears. These findings are discussed.
IMPORTANCE OF CALCIUM IN THE ACTIONS OF SOME DRUGS THAT STIMULATE THE ISOLATED HYPODYNAMIC FROG HEART
Authors: BROADBENT J. L.
Published: July 2012

Eight drugs that stimulate the isolated hypodynamic frog heart have been tested for their ability to stimulate hearts freshly perfused in calcium‐free Ringer solution. Ouabain and digitoxigenin regularly caused stimulation, veratridine did so occasionally. Hydrogen peroxide, tannic acid, paullinia tannin (from Paullinia pinnata, Linn.), sodium oleate and sodium caprylate did not stimulate. The stimulant action of ouabain could be prevented or greatly reduced by prior perfusion with either of the two tannins or with hydrogen peroxide. Hearts perfused for 3 to 4 hr with calcium‐free Ringer solution, or hearts perfused for shorter periods of time with calcium‐free Ringer solution containing the disodium salt of ethylenediaminetetra‐acetic acid, behave unusually in that when perfusion with low‐calcium Ringer solution is resumed twitch tension does not return for periods ranging from 10 to 90 min. Ouabain is unable to stimulate these “calcium‐depleted” hearts. It is suggested that hydrogen peroxide, the two tannins, oleate and caprylate stimulate by causing the heart to increase the uptake of calcium from the perfusion fluid to a superficial site where calcium is necessary for the propagation of excitation from the cell membrane inwards. A special feature of the action of cardiac glycosides may be their ability to enable the heart to utilize in a similar way the intracellular stores of calcium.
ACTIONS OF SOME PEPTIDES ON BRONCHIAL MUSCLE
Authors: BHOOLA K. D. , COLLIER H. O. J. , SCHACHTER M. , SHORLEY PATRICIA G.
Published: July 2012

The decapeptide kallidin‐10, substance P and angiotensin increased the resistance of guinea‐pig lungs to inflation; lysine‐ or arginine‐vasopressin and oxytocin were inactive. Acetylsalicylate antagonized this action of kallidin‐10, as it does that of bradykinin, but it failed to antagonize substance P or angiotensin. Bradykinin also increased resistance to inflation of rabbit lungs and, to a lesser extent, rat lungs. It caused a relatively slow contraction of guinea‐pig tracheal and bronchial muscle in vitro, but it did not contract isolated rabbit, dog or human bronchus. The relative potencies of different substances on different bronchial test preparations, and also in different species, were not parallel.
EFFECT OF ANTISYMPATHOMIMETIC DRUGS ON THE PLASMA CONCENTRATIONS OF CATECHOL AMINES
Authors: WILLEY G. L.
Published: July 2012

Intravenous injection of phenoxybenzamine, choline 2,6‐xylyl ether bromide (xylocholine, TM 10), piperoxane or dihydroergotamine increases the vasopressor activity of blood plasma, collected from cats under chloralose anaesthesia. The increased vasopressor activity that follows the administration of piperoxane is due to an increase of adrenaline and noradrenaline in the plasma. Cross‐circulation experiments show that catechol amines are liberated from the spleen by piperoxane.
DEPRESSION OF MUSCLE SPINDLE ACTIVITY—A NEW TYPE OF PHARMACOLOGICAL ACTION?
Authors: BEIN H. J. , FEHR H.‐U.
Published: July 2012

The effect of 2,4‐di(diethylamino)‐6‐(2‐phenylacetylhydrazino)‐1,3,5‐triazine (Ciba 28882‐Ba) injected intravenously on the activity of de‐efferented muscle spindles of the tibialis anterior and extensor digitorum longus muscles of anaesthetized cats, and on γ‐motoneurones of decerebrate cats, was investigated. The drug depressed both the static activity of muscle spindles and the spontaneous activity of γ‐motoneurones. In contrast, the response of muscle spindles to rapid stretch was not affected. The effect of 28882‐Ba on the activity of the muscle spindles resembled that of progressive unloading or shortening of the muscle. 28882‐Ba antagonized excitation of the muscle spindle by suxamethonium. The effect of 28882‐Ba on the response of the γ‐motoneurones to various driving stimuli was not predictable.
EFFECTS OF SOME GUANIDINE DERIVATIVES ON NEUROMUSCULAR AND GANGLIONIC TRANSMISSION
Authors: BARZAGHI F. , MANTEGAZZA P. , RIVA M.
Published: July 2012

The anticurare activity of some guanidine derivatives has been studied using the fowl sciatic nerve‐gastrocnemius muscle preparation and the cat sciatic nerve‐gastrocnemius and tibialis anterior muscle preparations. Among the compounds tested, and in decreasing order of potency, were NN‐dimethylguanidine, N‐methylguanidine, guanidine and N‐aminoguanidine which antagonized or prevented tubocurarine or gallamine triethiodide‐induced paralysis. None of the derivatives antagonized the effects of suxamethonium or decamethonium. NN‐Dimethylguanidine, N‐methylguanidine and guanidine antagonized or prevented the curare‐like effects of magnesium without altering the activity of hemicholinium. At high doses NN‐dimethylguanidine induced a decamethonium‐like spastic paralysis in the fowl sciatic nerve‐gastrocnemius muscle preparation. NN‐Diethylguanidine, however, induced a tubocurarine‐like flaccid paralysis. The derivatives possessing anticurare activity were also studied using the cat superior cervical ganglion‐nictitating membrane preparation to check their possible effects against ganglionic blocking agents. Only guanidine antagonized or prevented the effects of hexamethonium, pentolinium and mecamylamine; it had no effect on the actions of pempidine and chlorisondamine. NN‐Diethylguanidine was the only compound in the series to show a ganglionic blocking action.
AN ACTION OF 5‐HYDROXYTRYPTAMINE ON ADRENALINE RECEPTORS
Authors: INNES I. R.
Published: July 2012

Contractions of isolated strips of cat spleen due to 5‐hydroxytryptamine, adrenaline, histamine and acetylcholine were antagonized by phenoxybenzamine. Responses to both 5‐hydroxytryptamine and adrenaline were not blocked in strips which were protected by a high concentration of either 5‐hydroxytryptamine or adrenaline throughout exposure to phenoxybenzamine. The contraction due to a large dose of 5‐hydroxytryptamine lasted less than 1 hr even when the drug was still present. Strips thus desensitized to 5‐hydroxytryptamine responded normally to acetylcholine and histamine but did not respond to adrenaline. The actions of 5‐hydroxytryptamine and adrenaline were blocked by 2‐bromolysergic acid diethylamide or by dihydroergotamine. These results indicated that 5‐hydroxytryptamine and adrenaline act on the same receptors. Cocaine potentiated the action of adrenaline but inhibited the action of 5‐hydroxytryptamine. The sensitivity to 5‐hydroxytryptamine of spleen strips from cats treated 24 hr earlier with reserpine was only one‐fiftieth of that of normal strips. Cocaine potentiated the action of 5‐hydroxytryptamine on strips from reserpine‐treated cats. A high concentration of 5‐hydroxytryptamine in spleen strips from reserpine‐treated cats and in cocaine‐treated strips prevented phenoxybenzamine from blocking the actions of adrenaline. The effects of tyramine on spleen strips almost exactly paralleled the effects of 5‐hydroxytryptamine. Strips showing tachyphylaxis to tyramine did not respond to 5‐hydroxytryptamine. It is concluded that 5‐hydroxytryptamine has a dual action, viz., a major action due to release of stored noradrenaline and a minor direct action of adrenaline receptors.
EFFECT OF CHLORPROMAZINE, RESERPINE, BENACTYZINE AND PHENOBARBITONE ON THE RELEASE OF CORTICOTROPHIN IN THE RAT
Authors: ASHFORD A. , SHAPERO M.
Published: July 2012

A single injection into the rat of chlorpromazine, reserpine, benactyzine or phenobarbitone stimulates the release of corticotrophin. This effect is not seen after the drugs have been injected daily for 5 days, nor when the rats are hypophysectomized or pretreated with hydrocortisone. The stimulant effect of ether on corticotrophin release is not modified by pretreatment with a single injection, nor to any great extent after 5 daily injections of these drugs.
A COMPARISON BETWEEN THE EFFECTS OF A TETANUS AND THE EFFECTS OF SYMPATHOMIMETIC AMINES ON FAST‐ AND SLOW‐CONTRACTING MAMMALIAN MUSCLES
Authors: BOWMAN W. C. , GOLDBERG A. A. J. , RAPER C.
Published: July 2012

The effects of adrenaline and isoprenaline on the tension and time‐course of the contractions of the tibialis anterior and soleus muscles of cats and rabbits have been compared with the effects of previous high‐frequency stimulation. Like a tetanus, adrenaline possessed a facilitating action on neuromuscular transmission and an action exerted directly on the muscle fibres. Isoprenaline possessed only the second of these two actions. The effect of adrenaline and isoprenaline on the muscle fibres was blocked by dichloroisoprenaline and by 1‐(2 naphthyl)2‐isopropylaminoethanol, whereas the effect of adrenaline on neuromuscular transmission was blocked by phentolamine and by phenoxybenzamine. In the soleus muscle, both the catechol amines and a previous tetanus caused similar decreases in maximal twitch tension and in the times to peak tension and to half‐relaxation. The muscle action potentials were unaltered or slightly increased in amplitude. In the tibialis anterior muscle, a previous tetanus and the catechol amines caused an increase in twitch tension and an increase in the overall duration of the twitch. The muscle action potentials were either unchanged or were slightly decreased in amplitude. In this muscle the effect of a tetanus differed from that of the catechol amines in that the large post‐tetanic change was associated with a marked increase in the rate of rise of twitch tension.
ACTIVITY OF ANALOGUES OF DECAMETHONIUM ON THE CHICK BIVENTER CERVICIS PREPARATION
Authors: BARLOW R. B. , ZOLLER ANNE
Published: July 2012

The abilities of various decamethylenebisammonium compounds to cause contracture of the chick biventer cervicis preparation have been compared quantitatively with that of decamethonium. In the compounds tested the 1,10 substituents were similar and were ethyldimethylammonium, diethylmethylammonium, triethylammonium, hydroxyethyldimethylammonium and acetoxyethyldimethylammonium; decamethylenebisdimethylamine was also tested. The activity of the bisethyldimethylammonium compound is about one‐third of that of decamethonium, that of the bisdiethylmethylammonium compound about one‐twenty‐eighth, but the other compounds are much less than one‐hundredth as active. Even the bistriethylammonium compound, however, has some detectable activity although it is only a partial agonist. It is suggested that ability to depolarize the preparation depends upon the presence of methyl groups attached to the quaternary ammonium atom and also upon the presence of two such onium groups at the ends of the decamethylene chain. In these compounds the acetoxy group reduces ability to depolarize the preparation.
VASCULAR RESPONSES OF THE RAT TO BRADYKININ
Authors: LLOYD SYBIL
Published: July 2012

The effects of oestrogens and of sympathetic blockade on the vascular response of rats to bradykinin were studied. No difference in response was found between males and oestrous or dioestrous females. The previous administration of an oestrogen did not affect the response. An augmentation of the depressor response to bradykinin was seen in both sexes after the intravenous administration of either dihydroergotamine or hexamethonium, but not after atropine. Pithing reduced the response to bradykinin. The differences between these results and those previously obtained with oxytocin are discussed.
EVIDENCE FOR A COMPETITIVE ANTAGONISM OF GUANETHIDINE BY DEXAMPHETAMINE
Authors: DAY M. D. , RAND M. J.
Published: July 2012

After guanethidine had blocked the response of the cat nictitating membrane to sympathetic nerve stimulation, dexamphetamine restored the responses to all frequencies of stimulation. Dexamphetamine antagonized the sympathetic nerve block by guanethidine in the isolated sympathetically innervated rabbit ileum; the evidence suggests that the antagonism was competitive. Dexamphetamine antagonized the sympathetic nerve block by guanethidine in the isolated hypogastric nerve‐vas deferens preparation of the guinea‐pig. Doses of dexamphetamine, larger than those required to antagonize the blocking action of guanethidine, abolished the responses of the nictitating membrane, ileum and vas deferens to nerve stimulation. Dexamphetamine did not influence the depletion of noradrenaline by guanethidine in the heart and spleen of rabbits. The hypothesis is advanced that both dexamphetamine and guanethidine act on the store of noradrenaline at sympathetic nerve endings.
A FLUORIMETRIC METHOD FOR THE ESTIMATION OF 4‐HYDROXY‐3‐METHOXYPHENYLACETIC ACID (HOMOVANILLIC ACID) AND ITS IDENTIFICATION IN BRAIN TISSUE
Authors: SHARMAN D. F.
Published: July 2012

A fluorimetric method for the estimation of 4‐hydroxy‐3‐methoxyphenylacetic acid (homovanillic acid) has been developed and applied to normal brain tissue. The presence of homovanillic acid in the caudate nucleus of normal animals of several species has been demonstrated.
THE ACTION OF TYRAMINE ON THE DOG ISOLATED ATRIUM
Authors: HALL W. J.
Published: July 2012

It has been confirmed that tyramine has positive inotropic and chronotropic actions on the dog isolated atrium. These responses were incompletely and reversibly inhibited by cocaine, but completely and irreversibly blocked by phenoxybenzamine. Blockade of the atrial β‐receptors by dichloroisoprenaline could be overcome by noradrenaline and by larger doses of tyramine. With the aortic strip of the reserpinized rabbit for assay, tyramine was shown to release a vasoactive material from the dog atrium whose receptors were blocked by dichloroisoprenaline. The use of an anti‐histamine and an anti‐5‐hydroxytryptamine agent (cyproheptadine) appeared to exclude the possibility that the effect was due to the release of histamine or 5‐hydroxytryptamine from the atrium by tyramine. Further observations of the action of the vasoactive material on the guinea‐pig ileum and on the rat fundal strip strongly suggested that the material was a catechol amine. It was concluded that under these conditions tyramine acts by liberating catechol amines from storage sites so that the amines are free to act at receptor sites. The behaviour of the atrium to tyramine in the presence of cocaine or of phenoxybenzamine suggests that the liberation of catechol amines by tyramine differs from the release due to adrenergic nerve stimulation. It is suggested that, after an infusion of tyramine, there is a much slower release of catechol amines than after stimulation of adrenergic nerves.
THE ACTION OF SODIUM SALICYLATE AND ASPIRIN ON SOME KALLIKREIN SYSTEMS
Authors: HEBBORN P. , SHAW B.
Published: July 2012

The effects of sodium salicylate and of aspirin on the actions of pancreatic, salivary and serum kallikreins have been investigated. Kinin production by the three enzymes was assessed using a guinea‐pig isolated ileum preparation. The esterolytic activity of pancreatic and salivary kallikreins was measured by determining acid release from the synthetic substrate toluene‐p‐sulphonyl‐l‐arginine methyl ester. Sodium salicylate (up to 20 mM) or aspirin (up to 5 mM) failed to inhibit kinin production by each of the three enzymes. With salivary kallikrein, a concentration of 50 mM of sodium salicylate was required to produce a 50% inhibition of kinin production. No significant inhibition of esterolytic activity was produced by concentratioas up to 5 mM of either sodium salicylate or aspirin. Prior incubation of sodium salcylate or aspirin with the enzymes also resulted in no significant effect of either drug on kinin production or esterolytic activity. Prior incubation of pancreatic or salivary kallikrein with the inhibitor from ox parotid gland (Trasylol) reduced both kinin production and esterolytic activity. Toluene‐p‐sulphonyl‐l‐arginine methyl ester (0.5 mM) inhibited kinin production by each of the three enzymes. It is concluded that sodium salicylate and aspirin are poor inhibitors of kallikrein activity in vitro.
DOPAMINE‐β‐OXIDASE ACTIVITY IN MAN, USING HYDROXYAMPHETAMINE AS SUBSTRATE
Authors: SJOERDSMA A. , von STUDNITZ W.
Published: July 2012

Hydroxy amphetamine was administered orally to five human subjects in daily doses of 26 to 118 mg. Approximately half the dosage administered was recoverable in the urine as unchanged drug (free plus conjugated) and 3.7 to 9.1% was excreted as the β‐hydroxylated metabolite, hydroxynorephedrine (free plus conjugated). Since conversion of hydroxyamphetamine to hydroxynorephedrine occurs in vitro by the action of dopamine‐β‐oxidase, a simple method is suggested for measuring the activity of this enzyme and the effect of its inhibitors in man. No impairment of β‐hydroxylation was noted in an adrenalectomized subject. The β‐hydroxylation of hydroxyamphetamine in vivo has not been described previously.
THE EXCRETION OF PETHIDINE AND ITS DERIVATIVES
Authors: ASATOOR A. M. , LONDON D. R. , MILNE M. D. , SIMENHOFF M. L.
Published: July 2012

The excretion of pethidine and its metabolite norpethidine is increased in acid urine and decreased in alkaline urine. Excretion of these two bases is the main route of removal of pethidine from the body if the urine is highly acid. If the urine is alkaline, excretion of the hydrolysis products meperidinic and normeperidinic acids, both as free acids and as conjugates, is the more important means of elimination of the drug. Acidification of the urine with ammonium chloride is indicated in the therapy of cases of pethidine poisoning in patients with reduced metabolic breakdown of the drug by the microsomal enzyme systems within liver cells. Reversed‐phase chromatography of the dinitrophenyl derivative of norpethidine may prove to be of forensic importance in the diagnosis of pethidine poisoning or of pethidine addiction. Norpethidine can be detected in the urine by this method for at least 3 days after the last dose of pethidine. Analytical sensitivity is increased by acidification of the urine which produces a temporary rise of the excretion rate.
OBSERVATIONS ON THE ISOLATED VAS DEFERENS
Authors: OHLIN P. , STRÖMBLAD B. C. R.
Published: July 2012

Experiments on the isolated vas deferens of guinea‐pig and rat had unexpected results in several ways. The effect of stimulation of the hypogastric nerve was not abolished, but increased, by parasympathetic blocking agents or by sympathetic blocking agents such as dihydroergotamine and phenoxybenzamine. The sensitization is considered not due to anticholinesterase activity of the drugs. Prolonged contact with a stimulating agent evoked rhythmic contractions. Addition as well as removal of a drug from the bath caused a response. The results of experiments involving chronic denervation, addition of hexamethonium and histological examination tally with the assumption of a distribution of ganglionic cells along the nerve just outside the organ.
MECHANISM OF THE INITIAL ADRENERGIC EFFECTS OF BRETYLIUM AND GUANETHIDINE
Authors: GOKHALE S. D. , GULATI O. D. , KELKAR V. V.
Published: July 2012

Treatment with phenoxybenzamine and dichloroisoprenaline prevented the rise of blood pressure, contraction of the nictitating membrane and increase in cardiac contractile force produced by intravenous injections of bretylium and guanethidine in anaesthetized or spinal cats. Treatment with cocaine, imipramine or reserpine reduced the sensitivity to bretylium and guanethidine of the spinal cat. In the spinal cat treated with reserpine, sensitivity to the drugs could be restored by an infusion of noradrenaline. Chlorpromazine also blocked the pressor and nictitating membrane responses to bretylium and guanethidine. The drug effects were unaltered 1 hr after bilateral adrenalectomy. During the intravenous infusion of noradrenaline into spinal cats the pressor responses to bretylium and guanethidine were increased, whilst those to adrenaline and to noradrenaline were decreased. Guanethidine (3 to 5 mg/kg) injected intravenously into the cat caused a sudden relaxation of the rat isolated stomach‐strip bathed in blood. In seven similar experiments bretylium (3 to 5 mg/kg) relaxed the strip only once; in the other six experiments there was either no effect (four experiments) or an increase in the tone of the strip (two experiments). It is concluded that the initial adrenergic effects of bretylium and guanethidine are mediated, at least in part, through a release of catechol amines from stores in the effector organ.
ACTIONS OF TWO ALDOSTERONE ANTAGONISTS ON CAT PERFUSED KIDNEYS
Authors: LOCKETT MARY F. , ROBERTS C. N.
Published: July 2012

The actions of a closed‐ring [spironolactone, SC‐9420, β‐(7α‐acetylthio‐17β‐hydroxy‐3‐oxoandrost‐4‐en‐17α‐yl)propionic acid lactone] and of an open‐ring [SC‐11480, potassium β‐(17β‐hydroxy‐3‐oxoandrosta‐1,4‐dien‐17α‐yl)propionate] spirolactone have been examined on the cat perfused kidney, in concentrations ranging from 5 to 20 mg per 150 ml. of blood. Both compounds had weak aldosterone‐like effects and caused antidiuresis with retention of sodium, potassium and chloride. The urinary changes they induced summed with those of aldosterone, without competition. Neither spironolactone nor SC‐11480 affected renal blood flow or glomerular filtration rate. Both compounds antagonized the reduction in renal vascular resistance caused by aldosterone in these preparations.
ESTIMATION OF SUBSTANCE P IN MOUSE BRAIN. THE IDENTIFICATION OF INTERFERING NUCLEOTIDES IN THE EXTRACT
Authors: LASZLO I.
Published: July 2012

Substance P has been extracted from brain by previously described methods and assayed on the guinea‐pig isolated ileum. The concentrations showed a wide scatter which was not due to the bioassay or to variations in the extraction procedure. Adenosines‐monophosphate and adenosine‐5″‐triphosphate have been identified in the extracts by paper chromatography and by chemical reactions. The concentrations of these substances were sufficient to interfere with the assay of substance P, adenosine‐5″‐monophosphate diminishing and adenosine‐5″‐triphosphate increasing the contractions of the ileum due to substance P. Adenosine‐5″‐diphosphate was also detected in the extracts but its biological activity was insufficient to influence the estimations. The concentrations of adrenaline, noradrenaline, potassium ions, sodium chloride, 5‐hydroxytryptamine, and γ‐aminobutyric acid were below the threshold concentrations for interference with the assay of substance P.
THE EFFECT OF ANTIDEPRESSIVE DRUGS AND SOME RELATED COMPOUNDS ON THE LEVELS OF ADENINE NUCLEOTIDES, INORGANIC PHOSPHATE AND PHOSPHOCREATINE IN THE RAT BRAIN
Authors: LEWIS J. J. , VAN PETTEN G. R.
Published: July 2012

The effects upon levels of adenine nucleotides, phosphocreatine and inorganic phosphate of iproniazid, isoniazid, phenelzine, pheniprazine, tranylcypromine, harmine, imipramine, amitriptyline, orphenadrine, diphenhydramine and cocaine have been studied. With the exception of harmine and diphenhydramine, each of these compounds increased the brain level of adenosine triphosphate and, with the exception of imipramine and cocaine, the level of adenosine diphosphate decreased. Harmine had no effect on levels of adenine nucleotides and, in the case of diphenhydramine, the level of adenosine diphosphate increased and the level of adenosine triphosphate tended to decrease. There appears to be a relationship between the ability of the drugs to cause behavioural signs of central nervous stimulation and to produce an increase in the adenosine triphosphate/diphosphate ratio. This effect may be a factor in the action of antidepressive drugs.
IONTOPHORETIC RELEASE OF ADRENALINE, NORADRENALINE AND 5‐HYDROXYTRYPTAMINE FROM MICROPIPETS
Authors: KRNJEVIĆ K. , LAVERTY R. , SHARMAN D. F.
Published: July 2012

Estimations have been made of the amounts of adrenaline, noradrenaline and 5‐hydroxytryptamine released by iontophoresis from micropipettes. In most experiments, the amount released was linearly related to the total electrical charge, but the transport numbers for different pipettes, filled with samples of the same solutions of adrenaline or of noradrenaline, varied substantially. Two pipettes containing noradrenaline failed to release any appreciable amounts of the drug. The transport number of 5‐hydroxytryptamine was relatively constant (mean, 0.14).
SOME ENDOCRINE EFFECTS OF TWO PHENOTHIAZINE DERIVATIVES, CHLORPROMAZINE AND PERPHENAZINE, IN THE FEMALE MOUSE
Authors: JARRETT R. J.
Published: July 2012

The effects of chlorpromazine and perphenazine were studied with both immature and mature female mice. At a dose of 5 mg/kg daily, each drug delayed the onset of sexual maturity in immature animals. In mature mice, a daily dose of 10 mg/kg inhibited vaginal oestrus and reduced the weights of the ovaries, vagina and uterus. Each of the two drugs inhibited ovarian hypertrophy following unilateral ovariectomy, but only slightly diminished the responses to exogenous oestrogen and to exogenous gonadotropin. In one experiment, pseudopregnancy, as shown by a positive deciduoma‐test, was provoked by perphenazine, but this experiment could not be repeated. Chlorpromazine failed to evoke a positive deciduoma response. At a dose of 10 mg/kg, neither drug caused a fall in levels of adrenal ascorbic acid. In the rat, treatment for 1 week with 10 mg/kg daily of either drug led to a rise in pituitary gonadotropic activity. It was concluded that both drugs inhibited the release of gonadotropins by the pituitary gland, independently of any action in releasing corticotropin.
STUDIES ON WOUND HEALING
Authors: FENTON H. , WEST G. B.
Published: July 2012

Factors affecting the rate of healing of experimental skin wounds in rats have been investigated. The effectiveness of healing was measured by determining the tensile strengths of the incised skin after various time intervals. When the skin histamine content was lowered by treatment with polymyxin B or with compound 48/80, retardation of the healing process was evident from the reduced tensile strengths. When the skin 5‐hydroxytryptamine content was lowered by treatment with reserpine, retardation of healing was also found. Heparin increased the rate of healing and more rapid healing was obtained by giving histamine before each dose of heparin. On the other hand, some glucocorticoids markedly inhibited the healing process. Of the constituents of the tissue mast cells, heparin appears to be more important than histamine and 5‐hydroxytryptamine in promoting the healing of experimental skin wounds in rats.
THE RESPONSES TO TYRAMINE OF THE NORMAL AND DENERVATED NICTITATING MEMBRANE OF THE CAT: ANALYSIS OF THE MECHANISMS AND SITES OF ACTION
Authors: HAEFELY W. , HÜRLIMANN A. , THOENEN H.
Published: July 2012

The response to tyramine of the denervated nictitating membrane has been analysed by comparing dose/response curves obtained by injections into the femoral vein and into the carotid artery of the spinal cat while recording contractions of innervated and chronically denervated membranes and those of cats treated with reserpine. It is concluded that the effect of tyramine given by these routes is due primarily to catechol amines released from stores within the nictitating membrane itself. Higher doses of tyramine also cause contraction of the membrane by liberating catechol amines into the circulating blood from stores outside the membrane. The response to tyramine of the nictitating membrane after chronic denervation and/or prior treatment with reserpine is partially due to catechol amines released from unidentified stores within the membrane which resist depletion by reserpine and by postganglionic denervation; evidence is presented that adrenaline rather than noradrenaline is concerned. Because of the high sensitivity of the denervated nictitating membrane to adrenaline and to noradrenaline, the response to these amines released from stores outside the membrane by intravenous injections of tyramine becomes greater than that of the normal membrane. Dose/response curves obtained from responses to intravenous sympathomimetic drugs which act away from the membrane are therefore not fully representative of the effect of the drugs on the membrane itself. Tyramine probably has an affinity both for storage sites and for catechol amine receptors in the smooth muscle of the nictitating membrane, the “intrinsic activity,” however, being very weak or even absent.
DEPRESSION OF THE VASOMOTOR CENTRE BY MECAMYLAMINE, INDEPENDENT OF ITS GANGLION‐BLOCKING ACTIVITY
Authors: BHARGAVA K. P. , DHAWAN K. N.
Published: July 2012

Mecamylamine depressed the vasomotor centre independently of its ganglion‐blocking action. The central action was elicited by small amounts of the drug when it was confined to the central nervous system of dogs and cats anaesthetized with pentobarbital sodium and of spinal cats. The spinal site of action was shown by the inhibition of vasomotor responses due to spinal compression in cats, when mecamylamine was introduced intrathecally in a dose too small to block autonomic ganglia. The supraspinal site of action was shown by intravertebral arterial injection of mecamylamine into cats, which caused hypotension and selectively blocked the electrically evoked pressor responses from the medulla without affecting the “nicotinic” ganglionic responses to acetylcholine. Injection of mecamylamine into the cerebral ventricles of dogs produced hypotension, and the reflex vasomotor responses to stimulation of afferent fibres in the vagus nerves and to occlusion of the common carotid arteries were inhibited without any change in the response of the nictitating membrane to preganglionic nervous stimulation.
REMOVAL OF INTERFERING NUCLEOTIDES FROM BRAIN EXTRACTS CONTAINING SUBSTANCE P. EFFECT OF DRUGS ON BRAIN CONCENTRATIONS OF SUBSTANCE P
Authors: LASZLO I.
Published: July 2012

Several methods for removing interfering nucleotides, adenosine‐5″‐monophosphate and adenosine 5″‐triphosphate from brain extracts have been studied. An enzymic method, using adenylic acid deaminase, has been found suitable. This deaminates adenosine monophosphate to 5″‐inosinic acid, an inactive compound which does not influence the estimations of substance P. Owing to the adenosine triphosphatase content of the enzyme extract, adenosine triphosphate was also inactivated. For the estimation of adenosine monophosphate‐deaminase activity, a simple colorimetric method is described which measures the ammonia liberated from adenosine monophosphate. Substance P in mouse brain extracts was estimated after treatment of the animals with various drugs, and after the enzymic removal of interfering nucleotides from the brain extracts. The drugs had no effect on the substance P content of mouse brain. The effect of drugs on the contractions of the guinea‐pig ileum induced by substance P was also investigated, and the effect of drugs on the estimations of substance P in brain extracts is discussed.
CHEMOTHERAPY OF ARTHRITIS INDUCED IN RATS BY MYCOBACTERIAL ADJUVANT
Authors: NEWBOULD B. B.
Published: July 2012

Arthritis induced in rats by mycobacterial adjuvant has been used for the study of compounds of known value in the treatment of rheumatoid arthritis in man. The development of the arthritic syndrome in treated and control rats was followed by measuring the changes in foot thickness of both hind‐feet with a micrometer. This method allowed the effect of anti‐inflammatory compounds to be expressed quantitatively. Anti‐inflammatory activity was readily observed in certain steroids, pyrrolidines, salicylates and sodium aurothiomalate. Chloroquine and hydroxychloroquine were inactive. The inhibition obtained by daily treatment with the steroid paramethasone disappeared when treatment was withdrawn.
EFFECTS OF BRETYLIUM AND GUANETHIDINE ON HUMAN HAND AND FOREARM VESSELS AND ON THEIR SENSITIVITY TO NORADRENALINE
Authors: COOPER C. J. , FEWINGS J. D. , HODGE R. L. , WHELAN R. F.
Published: July 2012

Infusions of bretylium and guanethidine into the brachial artery of normal subjects caused a fall in forearm and hand blood flow followed by a sustained increase in flow. The constrictor phase was attributed to catechol amine release since it was blocked by phenoxybenzamine. A slight and transient increase in response of the hand vessels to noradrenaline was seen after bretylium in the early constrictor phase before sympathetic block was complete. Guanethidine produced a more definite and sustained increase in the response of the hand vessels to noradrenaline. It is concluded that the phenomenon of tolerance which is conspicuous with bretylium and negligible with guanethidine is unlikely to be due to the rapid onset of hypersensitivity of the peripheral vessels.
BRADYKININOGEN, ANGIOTENSINOGEN AND KALLIDINOGEN
Authors: FASCIOLO J. C. ,   With the technical assistance of A. MUÑOZ and H. SOSA
Published: July 2012

The plasma globulins which produce the vasoactive polypeptides, bradykinin, kallidin and angiotensin, have been compared. After incubation of plasma with kallikrein and exhaustion of its kallidinogen, subsequent incubation with trypsin did not result in formation of bradykinin, showing that bradykininogen had also been exhausted and suggesting that kallikrein and trypsin use the same substrate. Kallidin and bradykinin formation was not prevented by acid‐treatment of plasma, though heat‐denatured substrate produced kallidin less readily. Kallikrein could exhaust plasma bradykininogen without affecting levels of angiotensinogen. Following nephrectomy of dogs, plasma angiotensinogen levels rose whereas bradykininogen levels did not. These results confirm the belief that bradykininogen differs from angiotensinogen but not from kallidinogen.
EFFECT OF SOME BLOCKING DRUGS ON THE PRESSOR RESPONSE TO PHYSOSTIGMINE IN THE RAT
Authors: GOKHALE S. D. , GULATI O. D. , JOSHI N. Y.
Published: July 2012

Bretylium and guanethidine blocked the pressor effect of physostigmine and potentiated the responses to adrenaline and noradrenaline on the blood pressure of the rat. Morphine and atropine in small doses blocked the pressor effect of physostigmine without interfering with the actions of adrenaline and noradrenaline. Chlorpromazine in small doses (0.5 to 2.5 mg/kg) blocked the pressor effect of physostigmine and potentiated the responses to noradrenaline whilst those to adrenaline remained unaltered. 3, 6‐Di(3‐diethylaminopropoxy)pyridazine di(methiodide) (Win 4981) blocked the pressor effect of physostigmine and, in its early stages, this block was partially reversed by choline chloride. N‐Diethylaminoethyl‐N‐isopentyl‐N'N'‐diisopropylurea (P‐286), in a dose that reduced the effect of dimethylphenylpiperazinium, had no effect on the pressor response to physostigmine or on the responses to adrenaline and noradrenaline. Hexamethonium, even in large doses (100 mg/kg), only blocked partially the effect of physostigmine while mecamylamine produced a complete block; the responses to adrenaline and noradrenaline were potentiated in both instances.