bluuebunny/crossref_metadata_2025 huggingface dataset:
THE METABOLISM OF EXOGENOUS AND ENDOGENOUS ANTIDIURETIC HORMONE IN THE KIDNEY AND LIVER IN VIVO
Authors: HELLER H. , ZAIDI S. M. A.
Published: July 2012

Negligible antidiuretic activity (less than 0.17 mU./g.) was found in extracts of the kidneys either of unanaesthetized adult rats in normal water balance or of rats in whose blood a rise of the level of endogenous antidiuretic hormone had been induced by ether anaesthesia. Extracts of the livers of unanaesthetized rats had negligible antidiuretic activity (less than 0.06 mU./g.), but liver extracts from rats anaesthetized with ether showed antidiuretic effects equivalent to 0.74 ±0.24 mU. Pitressin/g. liver. When Pitressin was injected intravenously into unanaesthetized rats, small amounts of antidiuretic activity were occasionally found in the livers and the kidneys of animals killed up to 3 mm. after the injection but none in animals killed later. Some 3% of the antidiuretic activity of an injected dose of Pitressin was found in the urine and the “dead space” of the kidneys in rats decapitated 3 min. after the intravenous injection. When Pitressin was added to rat kidney homogenate and the mixture was incubated at 38°, only 0.75% of the initial antidiuretic activity was recovered after 30 min. and less than 0.<0% after 60 min. Experiments with “glomerular” and “tubular” fractions of rat kidney indicated that the inactivation was essentially due to tubular tissue. It is suggested that, in the rat, the kidneys and perhaps the liver are not only sites of clearance of the antidiuretic hormone but also sites of irreversible inactivation.
EFFECTS OF CHOLINE 2:6‐XYLYL ETHER BROMIDE UPON THE SUPRARENAL MEDULLA OF THE RAT
Authors: COUPLAND R. E. , EXLEY K. A.
Published: July 2012

The administration of choline 2:6‐xylyl ether bromide (TM 10) daily to rats for two weeks depletes the suprarenals of about one‐half their normal content of adrenaline and noradrenaline. This depletion has been demonstrated histologically and by colorimetric and biological estimation of the amines present in extracts of the glands. Treatment with TM 10 causes similar histological signs of depletion in autografts of adrenal chromaffin tissue in the rat iris. Restoration of catechol amines in rat suprarenals, previously depleted by TM 10, occurs slowly and appears to be complete 14 days after withdrawing the drug. These results, considered in conjunction with the estimated rate of turnover of catechol amines in the rat suprarenal, lend support to the view that TM 10 may interfere with the biosynthesis of these amines.
THE EFFECT OF CARRIER STRONTIUM ON THE ABSORPTION OF ORAL DOSES OF RADIOACTIVE STRONTIUM IN RATS
Authors: HARRISON G. E. , JONES H. G. , SUTTON A.
Published: July 2012

Carrier strontium had relatively little effect on the retention of an oral dose of radioactive strontium by the rat when it was administered immediately after the radioactive dose. The proportion of the radioactive dose which was excreted in the urine, on the other hand, increased progressively with the carrier dose. There was a decreased uptake of radioactive strontium in rats fed on a special low strontium diet. The effects of dietary strontium are discussed. Evidence was found of a discrimination by the rat against strontium in favour of calcium which was accounted for, at least in part, by a preferential urinary excretion of strontium.
THE PRESERVATION OF SUBSTANCE P BY LYSERGIC ACID DIETHYLAMIDE
Authors: KRIVOY W. A.
Published: July 2012

Lysergic acid diethylamide (LSD) potentiated the response of guinea‐pig ileum to substance P but not to histamine. It also inhibited the disappearance of substance P when incubated with guinea‐pig brain extract but not when incubated with chymotrypsin. Eserine, morphine, mescaline, chlorpromazine, ergometrine, strychnine and 2 bromo‐LSD did not have this effect. Oxytocin was not destroyed by brain extract. The inhibition of the destruction of substance P by LSD could be antagonized by 2 bromo‐LSD. This effect of LSD may have some relation to its pharmacological actions.
THE ANTITUBERCULOUS ACTIVITY OF ETHYL THIOLESTERS WITH PARTICULAR REFERENCE TO DIETHYL DITHIOLISOPHTHALATE
Authors: DAVIES G. E. , DRIVER G. W.
Published: July 2012

Diethyl dithiolisophthalate exerts an antituberculous effect in mice comparable to that of isoniazid and streptomycin. It is effective when given in single doses, and against isoniazid‐resistant strains. It is most active when given subcutaneously either by injection or by absorption through the skin. Drug resistance has been demonstrated in mice, and isoniazid is active against such strains. The effects of this and other ethyl thiolesters are antagonized by their methyl analogues.
ACTION OF ANAPHYLACTIC SHOCK AND ANAPHYLATOXIN ON MAST CELLS AND HISTAMINE IN RATS
Authors: MOTA IVAN
Published: July 2012

Anaphylactic shock in rats produces disruption of mast cells. These cells are also disrupted when rat mesentery is incubated with antigen in vitro. The plasma histamine reaches a maximum about 5 min. after injection of the antigen. Though antihistamines protect rats against anaphylactic shock, they do not prevent mast cell disruption. Previous depletion by compound 48/80 of the histamine bound to the mast cells prevents anaphylactic shock and the increase in plasma histamine. Anaphylatoxin produces no mast cell alterations or plasma histamine increase, and thus does not seem to act as a histamine‐releasing agent in rats. Probably nearly all the histamine liberated in anaphylaxis in rats comes from the mast cells.
THE EFFECT OF METHYLPENTYNOL IN MAN
Authors: DICKER S. E. , STEINBERG HANNAH
Published: July 2012

Administration of methylpentynol to human subjects depressed their autonomic reactions to a difficult motor task and impaired their performance. Hexobarbitone affected neither autonomic reactions nor performance, though it impaired hand steadiness. The results suggest that the modes of action of methylpentynol and of hexobarbitone are different.
THE ANTIDIURETIC ACTION OF 5‐HYDROXYTRYPTAMINE IN CATS IN RELATION TO THE PRODUCTION OF CERTAIN CHEMOREFLEXES
Authors: FASTIER F. N. , WAAL HENDRIEKA
Published: July 2012

In cats lightly anaesthetized with chloralose, small (5 to 50 μg./kg.) intravenous doses of 5‐hydroxytryptamine temporarily reduced the flow of urine into the bladder in addition to causing reflex falls of blood pressure and heart rate and temporary arrest of breathing. Doses of phenyl diguanide and other aryl diguanides, the reflex effects of which on blood pressure and respiratory movement approximately matched those of 5‐hydroxytryptamine, had comparatively little antidiuretic effect. Phenyl diguanide, unlike 5‐hydroxytryptamine (tested previously under similar conditions), did not have an antidiuretic effect in hydrated mice in doses of 0.05, 1, and 2.5 mg./kg. subcutaneously. It is concluded that the reflex depressor action of 5‐hydroxytryptamine plays little part in reducing urinary output.
THE ETHYLENEIMINIUM ION AS THE ACTIVE SPECIES IN 2‐HALOALKYLAMINE COMPOUNDS
Authors: GRAHAM J. D. P.
Published: July 2012

Certain 2‐haloethylamine compounds which exert antagonism to adrenaline and noradrenaline of the type shown by dibenamine have been examined. The compounds were N‐ethyl‐N‐chlorobenzyl‐2‐chloroethylamine hydrochlorides in which the Cl is in the p‐, o‐, and m‐ positions of the benzene ring, and the three related ethyleneiminium picrylsulphonates. In addition the Cl‐ and Br‐ compounds of the N‐ethyl‐N‐9‐fluorenyl‐2‐haloethylamine hydrohalide series were examined. For the haloethylamines, a curve was provided which showed the relation between probable production and decay of ethyleneiminium ion in neutralized solution with time. A correlation was established between the shape of this curve and the curve relating anti‐adrenaline and anti‐noradrenaline activity of samples of solutions of these compounds treated in an identical way. The relation to antagonism of histamine and 5‐hydroxytryptamine was not so exact and varied with species.

The ethyleneiminium ions of the three chlorobenzyl compounds exerted a typical long‐lasting non‐competitive antagonism to the pressor actions of adrenaline and noradrenaline. They also antagonized the effect of 5‐hydroxytryptamine and histamine on blood pressure. The ED50 of the ion when administered as ethyleneiminium picrylsulphonate was always less than the ED50 of the same ion when administered in the form of 2‐haloethylamine. There was, therefore, a variable loss of effective ion during transformation in vivo. The observations throw some light on the importance of the substituent groups on the nitrogen atom for effectiveness. It is concluded from these results and a discussion of other work that 2‐haloethylamine compounds form an ethyleneiminium ion in neutral solution, which is the pharmacologically active species in effective compounds. It is a necessary but not a sufficient condition that a molecule should be an alkylating agent for this type of antagonism to be present, but the importance of the substituent groups on the N atom is equally great because not all ethyleneiminium ions are effective antagonists.
THE EFFECT OF DIISOPROPYL FLUOROPHOSPHONATE ON THE SENSITIVITY OF RATS TO CENTRALLY ACTING DRUGS
Authors: BAYLISS BRENDA J. , ELKES J. , SPANNER SHEILA G. , TODRICK A.
Published: July 2012

The effect of a previous injection of an anticholinesterase, dyflos, on the sensitivity of rats to two centrally acting drugs, pentobarbitone and leptazol, has been measured. The sensitivity was determined at 12 and 35 days after birth and in full‐grown animals. Though the dose of dyflos was of the order of two‐thirds of the LD50, it did not affect the sensitivity of the young animals to sodium pentobarbitone and leptazol administered 20 hours later. The full‐grown animals which had received dyflos in arachis oil were more sensitive to sodium pentobarbitone than litter mates which had received an injection of arachis oil only; this difference was significant at the 0.1% level. The dyflos treatment did not significantly affect the sensitivity to leptazol.
EFFECTS OF RESERPINE ON BLOOD‐PRESSURE RESPONSES EVOKED FROM THE HYPOTHALAMUS
Authors: ANAND B. K. , DUA S. , MALHOTRA C. L.
Published: July 2012

Different areas of the hypothalamus were stimulated by a stereotaxic technique before and after reserpine in unanaesthetized cats. Reserpine in a dose of 1 mg./kg. body weight increased the threshold of stimulation of hypothalamic areas in cats giving an initial pressor response. It decreased the threshold of stimulation of areas of the hypothalamus in animals giving an initial depressor response. Reserpine thus appeared to affect the hypothalamus directly in two ways. It depressed the sympathetic centres in the diencephalon and facilitated the parasympathetic ones.
PHARMACOLOGICAL EFFECTS PRODUCED BY INTRACEREBRAL INJECTION OF DRUGS IN THE CONSCIOUS MOUSE
Authors: HALEY T. J. , McCORMICK W. G.
Published: July 2012

A method has been described for the study of the central effects produced by the intracerebral injection of drugs in the unanaesthetized mouse. The effects observed were in good agreement with those obtained after similar injections in cats, dogs and human beings. After intracerebral injection, drugs of diverse structure produced certain generalized effects: changes in positioning of the tail, stupor, hyperexcitability and tachypnoea. Both acetylcholine and methacholine produced an akinetic seizure and depression, but the latter compound also caused lacrimation and salivation. Atropine produced piloerection, increased sensitivity to sound and touch, clonic convulsions and scratching, whereas hexamethonium caused Parkinsonian‐like muscle tremors and peripheral vasodilatation. After adrenaline, hyperexcitability, exophthalmos, stupor and death from pulmonary oedema were observed, but (+)‐methylamphetamine produced only piloerection and exaggerated activity in response to sound and touch. Ergotamine caused a decreased sensitivity to sound and touch, micturition, and stupor, while ergometrine caused clonic convulsions, piloerection, defaecation and stupor.
SOME ASPECTS OF THE PHARMACOLOGY OF AN HOMOLOGOUS SERIES OF CHOLINE ESTERS OF FATTY ACIDS
Authors: SCHNEIDER R. , TIMMS A. R. , KYI ZU‐YOONG , WILSON W.
Published: July 2012

The pharmacological effects of a series of fatty acid‐choline esters have been studied on the isolated rabbit heart, the isolated guinea‐pig ileum and the rat stomach. The effect changed with increasing chain length, and three different types of response were observed. The short‐chain compounds produced depression of the isolated rabbit heart and spasm of the isolated guinea‐pig ileum. Only one, butyrylcholine, had an erratic stimulating effect on hydrochloric acid secretion by the partially vagotomized rat stomach. Medium‐chain compounds had a stimulating effect on the isolated rabbit heart, a mixed spasmogenic and relaxant effect on the isolated guinea‐pig ileum, and no effect on the rat stomach. Long‐chain compounds blocked the effect of acetylcholine on the isolated rabbit heart and the isolated guinea‐pig ileum; they also depressed spontaneous hydrochloric acid secretion by the rat stomach. The nature of these three types of response is discussed.
EXPERIMENTS WITH THE TRYPANOCIDAL COMPOUND “528” IN WEST AFRICA
Authors: CHANDLER R. L.
Published: July 2012

Studies have been made on the use of the chloride salt of “528” against cattle trypanosomiasis in Nigeria. Toxic effects, terminating in death, were produced in cattle receiving the drug at 5 mg./kg. and above. The maximum permissible dose for field use in Nigeria was found to be 2 mg./kg. The drug had an appreciable curative action against a syringe‐transmitted strain of T. congolense, but had no curative effect against two strains of T. vivax. It is concluded that “528” would be of very limited value in the treatment of cattle in West Africa, where T. vivax is the more important cause of cattle trypanosomiasis.
THE ANTIVIRAL ACTION OF THREO‐β‐PHENYLSERINE
Authors: DICKINSON LOÏS , THOMPSON MILDRED J. , NICHOLSON J. S.
Published: July 2012

l‐threo‐phenylserine and esters of threo‐phenylserine were the most active of a series of compounds tested against influenza A virus in tissue culture. Substitution of the β‐OH or α‐NH2 group abolished activity. The activity of phenylserine was reversed competitively by phenylalanine. Phenylserine did not act on free virus or on the adsorption of virus to host cells. It prevented virus growth if added during the first half of the latent period.

Phenylalanine appears to be necessary for virus synthesis and can be supplied by phenylalanylglycine or glycylphenylalanine.

Phenylserine had no significant activity against ectromelia infections in mice, even when the amino acid content of the livers had been depleted by starvation.
THE INFLUENCE OF POTASSIUM CONCENTRATION ON THE ACTION OF QUINIDINE AND OF SOME ANTIMALARIAL SUBSTANCES ON CARDIAC MUSCLE
Authors: ARMITAGE A. K.
Published: July 2012

The action of quinidine and some other antimalarial substances on cardiac muscle has been shown to be closely related to the K+ concentration of the surrounding medium. The depression of the amplitude and rate of the contractions of the isolated perfused rabbit heart and of the isolated rabbit atria which the antimalarial substances produced seems to be due to a diminution of the permeability of the membrane to K+, since it can be reversed by lowering the external K+ concentration. During exposure to any of the antimalarial compounds tested, the normal inhibitory action of acetylcholine was converted to a stimulant action. This stimulant action of acetylcholine is probably due to its effect in increasing the permeability of the membrane to K+. There were slight differences in behaviour between proguanil and quinidine on the one hand, and chloroquine, mepacrine and pyrimethamine on the other. The observations may explain the action of quinidine‐like substances in abolishing fibrillation.
THE ACTION OF MORPHINE ON THE SUPERIOR CERVICAL GANGLION AND ON THE NICTITATING MEMBRANE OF THE CAT
Authors: TRENDELENBURG U.
Published: July 2012

The intravenous injection of 0.05 to 2.5 mg. of morphine reduced the response of the nictitating membrane in the cat to pre‐ and post‐ganglionic stimulation. This inhibitory action of morphine was due neither to inhibition of ganglionic transmission nor to a depressant action on the smooth muscle of the nictitating membrane. It is suggested that morphine inhibits the release of the sympathetic transmitter from the postganglionic nerve endings.

Small amounts of morphine (5 to 20 μg.) injected intravenously reduced or abolished the contraction of the nictitating membrane due to the injection of histamine, pilocarpine and 5‐HT into the arterial blood supply of the superior cervical ganglion. This inhibitory action of morphine was due to an action on the ganglion cells, since such small amounts of morphine did not reduce the response of the nictitating membrane to postganglionic stimulation. Similar amounts of morphine did not abolish the stimulation of the ganglion by nicotine, tetramethyl‐ammonium and potassium chloride.

The results provide further evidence for the view that histamine, pilocarpine, and 5‐hydroxytryptamine have no “nicotine‐like” properties but act on receptors of the ganglion cells different from the acetylcholine receptors.
SEASONAL VARIATIONS IN THE RESPONSE OF RATS TO THE ANTIDIURETIC HORMONE
Authors: HELLER H. , HERDAN G. , ZAIDI S. M. A.
Published: July 2012

The antidiuretic response of unanaesthetized rats to intravenous doses of vasopressin has been compared in the different seasons of the year. Significant seasonal differences in sensitivity to the hormone were found; thus the rats responded to smaller doses in spring and summer. Discrimination between doses appeared to be best in summer. Relative variability in response seemed to be least in winter. There appeared from season to season to be a concomitant variation in the same or opposite direction between sensitivity in terms of the average minimum effective dose and environmental factors such as temperature, barometric pressure and relative humidity.
METABOLISM OF INJECTED [14C]HISTAMINE IN THE KIDNEY OF THE DOG
Authors: LINDELL S.‐E. , SCHAYER R. W.
Published: July 2012

In experiments on anaesthetized dogs, [14C]histamine was given in a steady infusion into one of the renal arteries, while urine was collected from both kidneys separately. The kidney which received the intra‐arterial injection of [14C]histamine excreted several times more [14C]‐labelled methylhistamine, methylimidazoleacetic acid and imidazoleacetic acid than did the other kidney, indicating that histamine may be inactivated in the canine kidney not only by histaminase but also by the histamine methylating enzyme.
THE RELATIONSHIP BETWEEN 5‐HYDROXYTRYPTAMINE AND ADENOSINE TRIPHOSPHATE IN BLOOD PLATELETS
Authors: BORN G. V. R. , INGRAM G. I. C. , STACEY R. S.
Published: July 2012

In normal platelets a proportionality was found between the amount of adenosine triphosphate (ATP) and amount of 5‐hydroxytryptamine (5‐HT) in platelets both before and after incubating them in plasma to which 5‐HT had been added. In patients receiving reserpine and in others with myeloid leukaemia, the amount of 5‐HT in the platelets and the uptake of 5‐HT by them were depressed, while the amount of ATP was normal. The possibility that ATP is involved in the accumulation of 5‐HT by platelets is discussed.
INHIBITION BY VARIOUS SUBSTANCES OF OEDEMA FORMATION IN THE HIND‐PAW OF THE RAT INDUCED BY 5‐HYDROXYTRYPTAMINE, HISTAMINE, DEXTRAN, EGGWHITE AND COMPOUND 48/80
Authors: PARRATT J. R. , WEST G. B.
Published: July 2012

Of the substances studied for their inhibitory action of the oedema formation in the hind‐paw of the rat, the most active was a new derivative of phenothiazine, related to chlorpromazine. It is methotrimeprazine {10‐(3‐dimethylamino‐2‐methylpropyl)‐2‐methoxyphenothiazine; 7044 RP}. This substance possesses potent antihistamine and anti‐5‐hydroxytryptamine properties, and doses ot 0.25 mg./kg. inhibited the blueing and swelling of the foot after injections of histamine, 5‐hydroxytryptamine, eggwhite, dextran or compound 48/80 into the feet of rats with sulphan blue (Evan's blue) dye in their circulation. The results indicate that both histamine and 5‐hydroxytryptamine play rôles in increasing capillary permeability in the rat.
THE ACTION OF ATROPINE ON PANCREATIC SECRETION
Authors: JUNQUEIRA L. C U. , ROTHSCHILD HANNA A. , VUGMAN I.
Published: July 2012

The action of atropine, in preventing pancreatic secretion in response to a parasympathomimetic drug, is analysed. Atropine does not appear to affect the uptake of glycine by the pancreatic cell, or the incorporation of radioactive amino acids into the total pancreatic tissue proteins, or into the proteins of the zymogen granules. The rate of amylase resynthesis in stimulated glands is not affected by atropine. It is suggested that atropine blocks pancreatic secretion in rats by blocking the extrusion of zymogen granules.
EFFECTS OF RAUNESCINE AND ISORAUNESCINE ON BEHAVIOUR AND ON THE 5‐HYDROXYTRYPTAMINE AND NORADRENALINE CONTENTS OF BRAIN
Authors: PAASONEN M. K. , DEWS P. B.
Published: July 2012

Some behavioural effects of raunescine and isoraunescine on pigeons have been studied; no qualitative difference was detected between their effects and those of reserpine. Isoraunescine is between five and ten times less potent than raunescine, which, in turn, is much less potent than reserpine in producing these effects.

Both raunescine (5 mg./kg.) and isoraunescine (50 mg./kg.) were found to cause a reduction in the concentration of noradrenaline in the brains of rats. Raunescine (5 mg./kg.) also caused a reduction in the concentration of 5‐hydroxytryptamine in brain; isoraunescine did not do so in the same dose; higher dose levels were not studied.
THE INFLUENCE OF CORTISONE AND HYDROCORTISONE ACETATES ON THE COURSE OF MYCOBACTERIUM LEPRAEMURIUM INFECTION IN RATS
Authors: BUTTLE G. A. H. , D'ARCY P. F. , HOWARD E. M.
Published: July 2012

Prolonged administration of cortisone acetate or hydrocortisone acetate produces a decrease in the rate of growth of treated rats. In this respect the effect of the latter steroid is the more pronounced. Lepromata in the steroid treated animals are significantly smaller than those in the control rats. This difference is more pronounced with the cortisone acetate treatment. However, whilst there is no appreciable difference in the distribution of organisms in the lepromata, the spread of infection is not increased by the steroid treatment, as the number of animals showing acid fast organisms in the spleen is no greater in the treated groups than in the controls.
SOME PHARMACOLOGICAL PROPERTIES OF MUREXINE (UROCANOYLCHOLINE)
Authors: KEYL M. J. , WHITTAKER V. P.
Published: July 2012

Murexine (urocanoylcholine, [2–β‐imidazol‐4(5)‐ylacryloyloxyethyl] trimethylammonium bromide) has been shown to possess ganglion stimulating and neuromuscular blocking actions in cat, dog and rat. The blockade has been shown to be of the depolarizing type both on the basis of the resemblance of the pharmacological properties of the substance to that of known depolarizing blocking agents, and also directly by recording the depolarization produced in the endplate region of the gracilis muscle of the rat.
A COMPARISON OF ANTIFIBRILLATORY DRUGS IN THE HEART‐LUNG PREPARATION
Authors: RAND M. J. , WALKER J. M.
Published: July 2012

Quinidine, amethocaine, Trasentin and atropine have been tested for their ability to stop atrial fibrillation produced in the heart‐lung preparation of the dog by stimulating the right atrium in the presence of acetylcholine. The results suggest that atropine acts by specifically antagonizing acetylcholine, but that amethocaine and Trasentin act chiefly by virtue of their quinidine‐like properties.
A COMPARISON OF SOME ACTIVITIES OF ARGININE VASOPRESSIN AND LYSINE VASOPRESSIN ON KIDNEY FUNCTION IN CONSCIOUS DOGS
Authors: ALI M. N.
Published: July 2012

Comparison was made on conscious trained dogs of the effect of highly purified arginine vasopressin and lysine vasopressin on the rate of urine flow, the excretion rate of Na and K and the renal clearances of creatinine and diodone, and of the actions of the vasopressins when administered together with oxytocin. The vasopressins were used in doses causing a maximal antidiuresis.

The results showed, first, that the antidiuretic potency of arginine vasopressin was greater than that of lysine vasopressin and that its action lasted longer; second, that during water diuresis arginine vasopressin increased only Na excretion while lysine vasopressin increased both Na and K excretion; third, that arginine vasopressin had a potency about 5 to 6 times that of lysine vasopressin in antagonizing the augmentor effect of oxytocin on glomerular filtration rate and renal plasma flow.
THE EFFECT OF ANTICHOLINESTERASES ON THE PAROTID GLAND AFTER PARASYMPATHETIC DECENTRALIZATION OR DENERVATION
Authors: EMMELIN N. , STRÖMBLAD B. C. R.
Published: July 2012

Anticholinesterases (eserine, ethyl pyrophosphate, paraoxon) were injected into the parotid ducts and found to cause a secretion of saliva. After previous preganglionic, parasympathetic denervation the effects were increased above normal; this was probably due to the supersensitivity to acetylcholine which develops after the operation. After previous postganglionic, parasympathetic denervation, on the other hand, the effects were much reduced, in spite of a pronounced supersensitivity towards, for example, acetylcholine. The cause of this “subsensitivity” towards Cholinesterase inhibitors is discussed.
A METHOD FOR RECORDING THE EFFECTS OF ANTHELMINTICS ON THE MOVEMENTS OF ASCARIS LUMBRICOIDES
Authors: GOODWIN L. G.
Published: July 2012

Adult roundworms (Ascaris lumbricoides) obtained from pigs were suspended in modified Tyrode solution at 37° in fine nylon stockings, and the movements of the stockings were recorded. This method of suspension avoided damage to the cuticle or occlusion of the alimentary tract of the worm.

Piperazine salts caused gradual narcosis, the time of onset of which was related linearly to the logarithm of the concentration of drug in the bath. The method is suitable for the assay of preparations of piperazine. Tetrachlorethylene, hexylresorcinol, and oil of chenopodium all caused stimulation of movement before the worm was immobilized. Santonin caused incoordination of the movements of the anterior end of the worm; the movements of the body were apparently unaffected. Piperazine is the safest preparation available for the treatment of ascariasis.
CARDIAC OUTPUT DURING EXCITATION OF CHEMOREFLEXES IN THE CAT
Authors: BARER GWENDA R. , NÜSSER E.
Published: July 2012

In cats under chloralose anaesthesia the reflex fall of blood pressure and heart rate caused by injection of veratrine, amidines, diphenhydramine, or ethyl acetoacetate was accompanied by a fall in cardiac output. After veratrine and amidines there was a fall in mean pulmonary arterial pressure and after veratrine no significant change in pulmonary vascular resistance. After diphenhydramine and ethyl acetoacetate there was a rise in mean pulmonary arterial pressure and after diphenhydramine an increase in pulmonary vascular resistance. The effects of veratrine and amidines, but not those of diphenhydramine and ethyl acetoacetate, were abolished by section of the vagi. The main change leading to the fall of cardiac output after amidines was bradycardia.
THE PHARMACOLOGICAL ACTIONS OF SOME MUREXINE‐LIKE SUBSTANCES
Authors: ERSPAMER V. , GLÄSSER A.
Published: July 2012

Four choline esters of imidazole acids, two imidazole ethers of choline and thirteen ring‐substituted murexine‐like compounds were compared with murexine for their muscle‐paralysing and their nicotine‐like effects. Dihydromurexine appeared, in animal experiments, to be the most potent derivative, but it was shown to be less effective than murexine in man. Among the other compounds, imidazolebutyrylcholine and imidazolepropoxycholine appeared to be worthy of particular consideration. The relation between the chemical structure of the murexine‐like substances studied and their pharmacological effects is discussed.
THE RELEASE OF ADRENALINE AND NORADRENALINE FROM THE ADRENAL MEDULLA OF THE CAT DURING SPLANCHNIC STIMULATION
Authors: BADE N. R. , WOOD D. R.
Published: July 2012

Cats were anaesthetized with chloralose, eviscerated and the right adrenal gland was removed. The venous outflow from the left adrenal gland was collected during 10 five‐minute periods of stimulation of the left splanchnic nerve. The amounts of adrenaline and noradrenaline in the venous outflow and in the stimulated and unstimulated glands were determined by a fluorimetric method. In eight experiments a mean of 50.5 μg. of total catechol amine was recovered from the effluent blood. The mean difference in amine content between the stimulated and unstimulated glands was 50 μg., representing a loss of 29% from the stimulated gland. The proportions of the two amines in the effluent blood were very similar to those found in the gland. The results provide no evidence for an increase in the rate of synthesis of catechol amines during splanchnic stimulation.
THE RELATIVE POTENCIES OF SOME SUBSTITUTED SALICYLIC ACIDS AS METABOLIC STIMULANTS IN THE INTACT RAT
Authors: ANDREWS MURIEL M.
Published: July 2012

The effects of eighteen substituted benzoic acids on the rate of oxygen consumption have been studied in rats. 2:3‐Dihydroxybenzoic acid, phthalic acid and 6‐methylsalicylic acid were, at the doses used, inactive; m‐ and p‐hydroxybenzoic acid, 2:4‐, 2:5‐, 2:6‐, 3:4‐, and 3:5‐dihydroxybenzoic acid, o‐aminobenzoic acid, salicyluric acid, salicylamide and 5‐amino‐salicylic acid decreased the rate of oxygen consumption. Only salicylic acid and o‐, m‐ and p‐cresotic acid (3‐, 4‐ and 5‐methylsalicylic acid respectively) increased the rate of oxygen consumption. Molar potency ratios of the cresotic acids as metabolic stimulants relative to salicylic acid were determined; o‐cresotic acid was the most powerful with a ratio of 2.61, m‐ and p‐cresotic acid had values of 1.78 and 1.89 respectively. Two possible explanations of the higher potencies of the cresotic acids were considered. No difference in the primary action of the drug was established by determining the effect on rate of oxygen consumption of a mixture of o‐cresotic and salicylic acids. An alternative possibility was that the rates of detoxication and excretion of the cresotic acids differed among themselves and from salicylic acid. No such differences were found.
THE DEPRESSOR ACTION OF DOPAMINE AND ADRENALINE
Authors: BURN J. H. , RAND M. J.
Published: July 2012

Dopamine is a pressor agent in the spinal cat, but causes a fall of blood pressure in the guinea‐pig and rabbit under urethane anaesthesia. When guinea‐pigs and rabbits are injected with reserpine, which depletes the vessel walls of noradrenaline, dopamine then becomes pressor. If an intravenous infusion of noradrenaline is given the depressor action returns. An intravenous infusion of vasopressin does not have this effect.

A strip of rabbit aorta is caused to contract by noradrenaline and by dopamine, but if dopamine is added at the height of a noradrenaline contraction it causes relaxation.

Adrenaline causes a fall of blood pressure in the cat under ether with vagi cut. However, in a reserpine‐treated cat its action is pressor. The depressor action is restored during an infusion of noradrenaline. Noradrenaline has thus been shown to cause a vasomotor reversal of dopamine and of adrenaline.
THE PERIPHERAL ACTION OF HEXAMETHONIUM AND OF PENTOLINIUM
Authors: MANTEGAZZA P. , TYLER CHRISTINE , ZAIMIS ELEANOR
Published: July 2012

The influence of hexamethonium and pentolinium on the responses of certain peripheral effector cells to adrenaline, noradrenaline or postganglionic stimulation was studied in the cat. The actions of adrenaline and noradrenaline on the blood vessels of a limb and of adrenaline and postganglionic stimulation on the nictitating membrane were increased after the administration of hexamethonium and pentolinium. This effect was considered to be due to sensitization of the peripheral effector cells. The possible significance of these findings is discussed.
EFFECTS OF DRUGS WHICH DEPRESS THE PERIPHERAL NERVOUS SYSTEM ON THE RETICULAR ACTIVATING SYSTEM OF THE CAT
Authors: EXLEY K. A. , FLEMING MARIE C. , ESPELIEN A. D.
Published: July 2012

Some drugs with depressant properties on the peripheral nervous system have been examined for depressant effects on the reticular activating system of the cat. Large doses of nicotine, or of the anti‐nicotinic agents dihydro‐β‐erythroidine and mecamylamine, failed to depress the reticular activating system; non‐quaternary drugs with anti‐muscarinic properties, such as atropine and hyoscine, depressed it readily. Hyoscine was the most potent depressant tested and its effects could be antagonized by physostigmine. In contradistinction, depression of the reticular activating system with pentobarbitone was not antagonized by physostigmine. Lignocaine was a weak depressant of the reticular activating system, and the possibility that this might be due to a central anti‐muscarinic action is discussed. Adrenergic blocking drugs, such as dihydroergotamine, phenoxybenzamine or choline 2: 6‐xylyl ether, did not appear to depress the reticular activating system: the significance of this is discussed. It was concluded that the hypothetical cholinergic transmitter, acting somewhere within the reticular activating system, displayed actions analogous to the muscarinic, and not to the nicotinic, actions of acetylcholine.
A COMPARISON OF SOME PHARMACOLOGICAL PROPERTIES OF DIOSCORINE AND DIOSCINE
Authors: BROADBENT J. L. , SCHNIEDEN H.
Published: July 2012

The alkaloids, dioscorine and dioscine, both obtained from yams, have been compared in respect of their convulsant activity, toxicity, analeptic action, local anaesthetic activity, adrenaline potentiating action, antidiuretic effect, and anti‐acetylcholine activity. The alkaloids have similar properties, but in most respects dioscorine was the more potent. Aqueous solutions of dioscine are unstable.
THE EFFECT OF DRUGS ON SPONTANEOUS MOTILITY AND ON RESPONSE TO STIMULATION OF THE EXTRINSIC NERVES OF THE GUT OF A TELEOSTEAN FISH
Authors: BURNSTOCK G.
Published: July 2012

Trout gut shows, in addition to changes in general muscle tone, longitudinal “pendular” rhythms, peristaltic waves, and longitudinal “colic” contractions. Both vagus and splanchnic nerves are motor and there is no evidence of antagonistic “sympathetic” and “parasympathetic” nervous control. A posterior autonomic nerve supplying the rectum stimulated or inhibited according to the duration and frequency of the electrical pulses applied. Acetylcholine increased the tone and amplitude of pendular movements in all regions of the gut, and produced strong contraction of the circular muscles. Both nicotine and hexamethonium antagonized the action of acetylcholine, suggesting that its principal site of action is the neurone. Adrenaline lowered the tone of the longitudinal muscle and abolished pendular activity in the intestine and rectum, but contracted the longitudinal and circular muscles of the stomach. Hexamethonium bromide abolished peristalsis but greatly increased the amplitude of pendular contractions.

The reaction of the trout intestine to both histamine and pilocarpine was slight, but nicotine, 5‐hydroxytryptamine, eserine, and barium caused strong contractions. The actions of atropine and piperoxan (933F) are discussed. Evidence is presented which suggests that the postganglionic vagus nerve fibres supplying the trout stomach may be adrenergic, while both the splanchnic nerve fibres to the stomach and intestine, and the preganglionic vagal fibres to the stomach, may be cholinergic. It is also suggested that there is a continuous release of acetylcholine by cholinergic neurones in the gut wall.
SUPERSENSITIVITY OF THE VESSELS OF THE PAROTID GLAND AFTER DENERVATION
Authors: OHLIN P. , STRÖMBLAD B. C. R.
Published: July 2012

Section of the postganglionic parasympathetic nerves to the parotid gland of the cat was found to cause supersensitivity of the blood vessels of the gland towards adrenaline. No supersensitivity or a slight degree only was found after cutting the preganglionic parasympathetic nerves to the gland. No supersensitivity of the vessels of the parotid gland could be demonstrated after excision of the superior cervical ganglion.
EFFECT OF PYRIDINE ALDOXIMES ON RESPONSE OF FROG RECTUS MUSCLE TO ACETYLCHOLINE
Authors: FLEISHER J. H. , HOWARD J. W. , CORRIGAN J. P.
Published: July 2012

The effects of pyridine‐2, 3‐ and 4‐aldoxime methiodide (PAM) on the isotonic contracture of the isolated frog rectus abdominis muscle elicited by acetylcholine have been studied. The potentiation to acetylcholine resulting from incubation with PAM isomers is reversible and may be related to the weak anticholinesterase property of these compounds. Concentrations of the isomers higher than those needed for maximal potentiation produce a reversible block of the muscle to acetylcholine. pH studies suggest that cations are responsible for the potentiating and blocking properties of the PAM isomers.
ABSENCE OF RENAL ACTION OF PURE INTERMEDIATE LOBE HORMONE
Authors: CROSS R. B.
Published: July 2012

The action of melanophore expanding hormone of the intermediate lobe of the pituitary (MSH) on the urinary excretion of water, Na, K and Cl was studied in the conscious dog both during water diuresis and in the non‐diuretic state. Doses of up to 2.3 IU MSH did not influence renal function. MSH did not modify the renal actions of vasopressin or oxytocin. The antidiuretic action of a massive dose of MSH was attributed to contamination by vasopressin.
ACTION OF DIETHYLCARBAMAZINE IN VITRO ON INFECTIVE LARVAE OF WUCHERERIA BANCROFTI
Authors: JORDAN P.
Published: July 2012

Infective larvae of Wuchereria bancrofti were obtained from laboratory infected Culex fatigans and maintained in serum containing diethylcarbamazine. There was no difference in the survival time of these larvae and larvae maintained in control serum without diethylcarbamazine. In one of the three experiments reported the survival time of the larvae was much longer than in the other two experiments. It is suggested that this may have been due to the presence of filarial antibodies which killed the larvae in two of the sera used. In the serum which did not contain antibodies, the larvae survived very much longer.
ACTIONS OF SCORPION VENOM ON SKELETAL MUSCLE
Authors: ADAM K. R. , WEISS C.
Published: July 2012

A protein‐like constituent of scorpion venom produced effects on the skeletal muscle fibre resembling those of citrate, lack of calcium or veratrine. These effects could be diminished by the addition of calcium. They do not appear to be due to the formation of a non‐ionized complex with calcium.
A COMPARATIVE STUDY OF THE EFFECTS OF DRUGS ON THE AROUSAL SYSTEM OF THE BRAIN
Authors: BRADLEY P. B. , KEY B. J.
Published: July 2012

The effects of twelve drugs, eleven of which are reported to be tranquillizers, have been studied in relation to thresholds for arousal produced both by direct stimulation of the brain stem reticular formation and also by afferent nerve stimulation. The drugs can be grouped according to whether (a) like chlorpromazine they produce a slight rise in thresholds for brain stem stimulation and block sensory‐induced arousal, (b) cause dissociation between behaviour and electrical activity of the brain, (c) have no effects on thresholds for brain stem stimulation and only slight effects on afferent nerve‐induced arousal or (d) have no effect on arousal responses at all.
THE ANALYSIS OF DRUG‐INDUCED TREMOR IN MICE
Authors: AHMED A. , TAYLOR N. R. W.
Published: July 2012

An improved method of recording tremor in mice has been developed using a gramophone pick‐up and a cathode ray oscillograph. Permanent records are made on 35 mm. film from which it is possible to determine qualitative differences in the tremor caused by various drugs. In addition, the severity of the tremor may be estimated quantitatively by a tremor index. The rate and variations in the rhythm and amplitude and in the tremor index have been determined for Tremorine (1,4‐dipyrrolidin‐1′‐ylbut‐2‐yne), harmine, harmaline, 3‐amino‐1,1,3‐triphenylpropan‐1‐ol and lysergic acid diethylamide. The incidence of side effects has also been noted.
OBSERVATIONS ON THE SUBSTRATE SPECIFICITY OF AMINE OXIDASES
Authors: BLASCHKO H. , CHRUŚCIEL T. L.
Published: July 2012

A number of compounds have been tested as substrates of, first, the amine oxidases of rabbit and guinea‐pig liver and of goat, pig, horse, and dog plasma and, second, the “diamine oxidase” of pig kidney. Of the three xylylenediamines [di(aminomethyl)benzenes] tested, m‐xylylenediamine was found to be a substrate of the liver oxidase. All the plasma oxidases tested acted on both m‐ and o‐xylylenediamine. Both 3‐ and 4‐picolylamine (3‐ and 4‐aminomethylpyridine) were readily oxidized by the liver enzymes; all the plasma oxidases tested oxidized 2‐, 3‐, and 4‐picolylamine. 4‐Picolylamine was more rapidly oxidized by horse and dog plasma than any other substrate hitherto examined.
THE EFFECTS OF LOADING RATS WITH INTRAVENOUS ISOTONIC SODIUM CHLORIDE ON THE RENAL RESPONSE TO DIURETICS
Authors: KEELER R. , SCHNIEDEN H.
Published: July 2012

The effect of a number of diuretic agents was investigated on rats with different degrees of expansion of extracellular fluid volume. With moderate saline loading aminoisometradine and chlorthiazide were the most efficient diuretics. However, with a more severe saline load aminoisometradine and mersalyl had the greatest effect while chlorthiazide had no significant diuretic activity. The action of acetazolamide seemed independent of the saline load. Potassium chloride showed no diuretic activity. Injecting the drugs in pairs resulted in probable potentiation only with acetazolamide plus chlorthiazide. Since all the diuretics were used in doses which gave maximal effects, the summation of the effects of the other pairs of diuretics suggested different sites of action.
THE ACTION OF ANTISYMPATHOMIMETIC DRUGS ON THE URINARY EXCRETION OF ADRENALINE AND NORADRENALINE
Authors: BENFEY B. G. , LEDOUX G. , SEGAL M.
Published: July 2012

In cats anaesthetized with pentobarbitone sodium, phenoxybenzamine, dibenamine, phentolamine, and piperoxane reduced the blood pressure and increased the urinary excretion of noradrenaline. When the fall of blood pressure after phenoxybenzamine was prevented by repeated injections of vasopressin, the urinary excretion of noradrenaline did not rise. Hydergine and hydrallazine reduced the blood pressure without raising the urinary excretion of noradrenaline. In dogs, the infusion of small amounts of noradrenaline led to a significantly higher urinary recovery of the amine after phenoxybenzamine than before. It is concluded that anti‐sympathomimetic drugs interfere with the destruction in the body of noradrenaline, whether released reflexly in hypotension or injected.
THE PHARMACOLOGY OF A MOLLUSCAN SMOOTH MUSCLE
Authors: TWAROG BETTY M.
Published: July 2012

The effects of a number of pharmacologically active substances on contraction and on membrane polarization of the anterior byssal retractor muscle of Mytilus edulis, L., have been studied. Tetramethylammonium bromide, trimethyl(4‐oxopentyl)ammonium chloride and nicotine, like acetylcholine, produced depolarization and sustained contraction. Nicotine, on repeated application, lost acetylcholine‐like activity and effectively blocked acetylcholine. In order of decreasing potency, methanthelinium, tubocurarine, benzoquinonium, tetraethylammonium, atropine, pentamethonium, and decamethonium blocked acetylcholine action. These agents did not show initial acetylcholine‐like action and did not relax sustained contractions. Adrenaline, noradrenaline, tyramine, dibenamine, phentolamine, and lysergic acid diethylamide relaxed sustained contractions without reducing initial depolarization and tension development in response to acetylcholine or electrical stimuli. Adrenaline and noradrenaline often caused depolarization and contraction when first applied, and displayed relaxing action on subsequent application.
THE EFFECT OF NITROFURAZONE ON TRYPANOSOMA RHODESIENSE INFECTIONS IN MICE
Authors: BAKER J. R.
Published: July 2012

Mice infected with a freshly isolated strain of Trypanosoma rhodesiense were not cured by ten daily intraperitoneal doses of 50, 100, 200, or 400 mg./kg. of nitrofurazone (5‐nitrofurfuraldehyde semicarbazone). At the highest dosage used, the drug was lethal to some of the mice.
2‐HYDROXYIMINOMETHYL‐N‐METHYLPYRIDINIUM METHANESULPHONATE AND ATROPINE IN THE TREATMENT OF SEVERE ORGANOPHOSPHATE POISONING
Authors: DAVIES D. R. , GREEN A. L. , WILLEY G. L.
Published: July 2012

The soluble methanesulphonate of the oxime 2‐hydroxyiminomethyl‐N‐methylpyridinium (P2S) has been used to treat animals poisoned with sarin or ethyl pyrophosphate. The effect of the size of the dose, and its time of administration in relation to poisoning, have been examined. This oxime is very efficient in conjunction with atropine when given either before or after poisoning. About 30 mg./kg. seems to be the optimum therapeutic dose of the methanesulphonate. The significance of this optimum is discussed in relation to the treatment of accidental poisoning by organophosphate insecticides in man.
PLASMA ADRENALINE AND NORADRENALINE AFTER PHENOXYBENZAMINE ADMINISTRATION, AND DURING HAEMORRHAGIC HYPOTENSION, IN NORMAL AND ADRENALECTOMIZED DOGS
Authors: MILLAR R. A. , KEENER E. B. , BENFEY B. G.
Published: July 2012

The intravenous administration of the antiadrenaline drug phenoxybenzamine (Dibenzyline) markedly raised the arterial adrenaline and noradrenaline concentration in dogs lightly anaesthetized with thiopentone. Graded haemorrhage led to a further rise in the amounts of amine. In adrenalectomized dogs, phenoxybenzamine moderately increased the plasma noradrenaline concentration. During haemorrhagic hypotension, previous treatment of adrenalectomized animals with phenoxybenzamine led to a significantly greater rise in plasma noradrenaline compared with that of adrenalectomized animals subjected to haemorrhage without treatment with phenoxybenzamine. Thus, phenoxybenzamine (1) raised plasma amine concentration largely due to adrenal medullary stimulation, and (2) led to increased plasma noradrenaline concentrations during sympathetic stimulation in adrenalectomized animals. The previous administration of phenoxybenzamine reduced the amount of blood which could be withdrawn before final circulatory collapse in both normal and adrenalectomized dogs.