bluuebunny/crossref_metadata_2025 huggingface dataset:
TWO KINDS OF TRYPTAMINE RECEPTOR
Authors: GADDUM J. H. , PICARELLI Z. P.
Published: July 2012

There are two kinds of tryptamine receptor in the guinea‐pig ileum, namely the M receptors which can be blocked with morphine and the D receptors which can be blocked with dibenzyline. Atropine, an atropine‐like drug, cocaine, and methadone inhibit effects due to the M receptors, even after dibenzyline, but have no additional effect after morphine. Lysergic acid diethylamide, dihydroergotamine and 5‐benzyloxygramine inhibit effects due to the D receptors, even after morphine, but have no additional effect after dibenzyline. The M receptors are probably in the nervous tissue and the D receptors are probably in the muscles.
THE ACTION OF SUBSTANCES ANALOGOUS TO DIAMINODIPHENOXYALKANES AGAINST SCHISTOSOMA MANSONI
Authors: GORVIN J. H. , RAISON C. G. , SOLOMON W. , STANDEN O. D. , WALLS L. P.
Published: July 2012

The effects on activity against Schistosoma mansoni of further modifications of the diaminodiphenoxyalkanes are reported. Replacement of the amino‐group by any of a large number of other groups destroys activity. Activity is retained in the presence of certain substituted (hydroxyalkyl, carboxyalkyl) amino‐groups and in some of their aldehyde‐bisulphite derivatives. Many variations of the central chain lead to compounds of reduced activity, the outstanding exceptions being a number of but‐2‐ene derivatives, which retain full activity.
THE EFFECTS OF NICOTINE, HEXAMETHONIUM AND ETHANOL ON THE SECRETION OF THE ANTIDIURETIC AND OXYTOCIC HORMONES OF THE RAT
Authors: BISSET G. W. , WALKER J. M.
Published: July 2012

The actions of nicotine, hexamethonium, and ethanol on the hypothalamo‐hypophysial system have been investigated in the rat. The antidiuretic action of nicotine was not inhibited by ethanol, nor by doses of hexamethonium which were sufficient to block both its pressor and convulsant actions. Hexamethonium itself had an antidiuretic action the mechanism of which has been investigated. Nicotine caused a release of oxytocin into the blood which was not blocked by ethanol nor significantly reduced by hexamethonium. The results suggest that any synapse which exists at the supraoptic nuclei is dissimilar in its pharmacological properties to synapses at autonomic ganglia.
THE TOXICITY OF DIAMINODIPHENOXYALKANES
Authors: GOODWIN L. G. , RICHARDS W. H. G. , UDALL V.
Published: July 2012

Representative members of a series of schistosomicidal diaminodiphenoxyalkanes were examined for their toxic effects in laboratory animals. Primary amino‐derivatives were, in general, more toxic than secondary methylamino‐compounds; tertiary compounds were less toxic than either. Large doses given by mouth or by injection to mice or rabbits produced intravascular haemolysis; the haemoglobin and erythrocyte counts began to increase again about a week after the dose. Mice which had been given large doses of diaminodiphenoxyalkanes developed symmetrical bald patches 2 to 3 weeks after treatment. The exposed skin appeared normal and new fur grew to cover the hairless areas in about 6 weeks. Large doses of drug delayed water diuresis in mice.

Many compounds of the series caused visual impairment when given to cats. In order to obtain a quantitative assessment of retinotoxic potency, a method was devised in which the ability of the retina of the frog to resynthesize rhodopsin was measured in treated and control animals. Compounds that produced blindness in cats also inhibited rhodopsin synthesis in frogs; the most toxic compounds were primary amines. Treatment with some tertiary amines caused retinal damage if the drugs were given for long periods. Diaminodiphenoxyalkanes may perhaps interfere in some way with the biological activity of vitamin A. However, toxic effects on the hair and retina were not prevented by supplements of synthetic or natural vitamin A.
METABOLIC AND OTHER EFFECTS OF RESERPINE UPON SMOOTH AND SKELETAL MUSCLE
Authors: GILLIS C. N. , LEWIS J. J.
Published: July 2012

Reserpine increased the concentration of potassium ions in the fluid bathing the isolated frog sartorius muscle. The effect of reserpine upon respiration and upon glycolysis in rabbit intestinal muscle has been investigated using the Warburg “Direct” method. After a latent period, reserpine (50 μg./ml.) depressed respiration but did not affect glycolysis in gut muscle. These results, together with previous observations, may point to an effect of reserpine upon carbohydrate metabolism.
THE ACTION OF TRIETHYLENEMELAMINE ON THE FERTILITY OF MALE RATS
Authors: BOCK MARION , JACKSON H.
Published: July 2012

Small doses of triethylenemelamine (TEM) had a selective action on the fertility of male rats. One dose (0.2 mg./kg., i.p.) produced effects ranging from subfertility to sterility during the next 3 weeks. In the fourth week sterility was the rule, but normal fertility was restored in the fifth week. A short course of the drug (5 daily doses, 0.2 mg./kg., i.p.) resulted in sterility lasting about 5 weeks, after which fertility was rapidly regained. Daily doses (0.05 mg./kg., i.p.) caused infertility in about a week which was maintained throughout treatment (7 weeks), and persisted for several weeks after the drug was discontinued. Sexual activity of infertile animals seemed normal and sperm production appeared to continue. Spermatozoa from infertile animals were able to reach and penetrate ova. The results suggest that TEM acts directly on the germinal epithelium. An attempt has been made to provide some explanation for these results and correlate them with the time required for spermatogenesis.
THE INHIBITION BY SODIUM SALICYLATE OF OEDEMA OF THE HIND‐PAW OF THE RAT INDUCED BY 5‐HYDROXYTRYPTAMINE
Authors: KELEMEN E.
Published: July 2012

The subcutaneous administration of 600 mg./kg. body weight of sodium salicylate to adult rats 3 to 4 hr. previously inhibited the development of hind‐paw oedema following the injection of 2.5 μg. of 5‐hydroxytryptamine. This effect was more pronounced in normal than in adrenalectomized rats.
THE ASSAY OF ANTI‐ACETYLCHOLINE AGENTS FOR ANTAGONISM OF PILOCARPINE‐INDUCED SALIVATION IN RABBITS
Authors: BROWN D. M. , QUINTON R. M.
Published: July 2012

Experimental conditions affecting tests of atropine‐like agents for antagonism of pilocarpine‐induced salivation in rabbits have been examined. A simple method of assay of such agents is described. It gave results of fair accuracy and reproducibility, permitted a full statistical analysis, and provided an estimate of the error.
THE TRANSMITTER RELEASED BY STIMULATION OF THE BRONCHIAL SYMPATHETIC NERVES OF CATS
Authors: LOCKETT MARY F.
Published: July 2012

A study has been made of the transmitter released in a cat heart‐lung preparation when the sympathetic chains were stimulated. The nervi accelerantes were always sectioned before stimulation. The transmitter appeared first in the pulmonary venous blood. In its actions on the heart‐lung preparation, it resembled isoprenaline and not adrenaline. Chromatographic studies using three different solvents showed that 80 to 100% of this transmitter consisted of a catechol amine which had RF values which were identical with those of isoprenaline. Pharmacological studies failed to distinguish between the actions of this amine and those of isoprenaline, but clearly differentiated between those of the pulmonary amine, adrenaline, and noradrenaline.
SENSITIZATION OF THE HEART AND NICTITATING MEMBRANE OF THE CAT TO SYMPATHOMIMETIC AMINES BY ANTIHISTAMINE DRUGS
Authors: INNES I. R.
Published: July 2012

Sensitization to the cardio‐accelerator action of adrenaline and noradrenaline by five antihistamines was examined on the acutely denervated heart of the cat. Antazoline (Antistin), chlorcyclizine and promethazine (Phenergan) increased the cardio‐accelerator responses to both amines equally. Mepyramine (Anthisan) increased noradrenaline more than adrenaline action. Diphenhydramine (Benadryl) resembled cocaine in potentiating the responses to noradrenaline but not to adrenaline.

On the nictitating membrane mepyramine caused sensitization to the actions of adrenaline, noradrenaline and tyramine, an effect similar to that of chronic preganglionic denervation. Diphenhydramine enhanced the action of noradrenaline more than that of adrenaline and had little effect on tyramine action, giving a sensitization which bears a greater resemblance to the type caused by cocaine or chronic postganglionic denervation.

It is suggested that two distinct mechanisms are required to account for the phenomena of sensitization.
AN INHIBITORY EFFECT OF ACETYLCHOLINE ON THE RESPONSE OF THE GUINEA‐PIG ILEUM TO HISTAMINE
Authors: DALE M. MAUREEN
Published: July 2012

If small doses of histamine are alternated with small doses of acetylcholine on the isolated guinea‐pig ileum in Tyrode solution, the response to histamine tends to diminish and may disappear. When the response to the small doses of histamine has disappeared, a contraction may be elicited by larger doses. The diminution is reversible, the response returning if the preparation is left unstimulated by drugs for varying periods of time. This phenomenon also occurs when the loops are suspended in Tyrode solution containing cocaine or atropine.
ANALGESIC ACTIVITY OF (+)‐1‐(3‐METHYL‐4‐MORPHOLINO‐2:2‐DIPHENYLBUTYRYL)PYRROLIDINE (R.875) IN STUDENT VOLUNTEERS
Authors: CAHAL D. A.
Published: July 2012

(+)‐1‐(3‐Methyl‐4‐morpholino‐2:2‐diphenylbutyryl)pyrrolidine (R.875) raised the threshold to ischaemic pain in healthy human volunteers. The peak effect for all doses was reached after about 2 hr. The drug frequently caused nausea and vomiting but no euphoria. Muscular weakness was experienced by many subjects and was sometimes followed 1 to 2 hr. later by hiccup and muscle twitching, suggesting that R.875 may have an effect on striped muscle.
FORMATION OF HISTAMINE IN THE KIDNEY OF THE DOG
Authors: LINDELL S.‐E. , SCHAYER R. W.
Published: July 2012

In dogs [14C]l‐histidine was given in a steady infusion into one renal artery while urine was collected from both kidneys separately. The urine from the infused kidney contained considerably more [14C]histamine than did the urine from the other kidney. The difference between the kidneys in the amounts of [14C]histamine appearing in the urine was considered to be due to formation of histamine from histidine in the injected kidney. It is concluded that histamine formed in the kidney may contribute to the urinary histamine.
CHRONIC TOXICITY OF DEXTRAN SULPHATE IN RABBITS
Authors: HINT H. C. , RICHTER A. W.
Published: July 2012

The chronic toxicities of two samples of low molecular dextran sulphate from different sources were studied in rabbits. Both samples caused retardation in weight gain, cachexia and general osteoporosis with spontaneous fractures and epiphyseolyses. Heparin‐treated controls were used to exclude the possibility that the toxic effects could be connected with prolonged anticoagulant treatment. It is concluded that prolonged administration of dextran sulphate causes systemic toxic effects which are not related to its anticoagulant activity.
VASOACTIVE SUBSTANCES IN THE NASAL MUCOSA
Authors: TOH C. C. , MOHIUDDIN A.
Published: July 2012

Besides histamine another smooth muscle stimulating substance has been found in the nasal mucosa of dog and sheep. It is an acid which is readily oxidized by neutral aqueous potassium permanganate and osmium tetroxide, and is thermostable at pH 10·8 but not at pH 2·8. The purification of this acid has been followed by using the atropinized tortoise intestine as a test object, which is insensitive to acetylcholine, 5‐hydroxytryptamine and small amounts of histamine. Both the tortoise intestine and rat colon are contracted by this acidic substance. The amount of histamine found in sheep nasal mucosa ranged from 12 to 23 μg./g. tissue and in dog nasal mucosa from 6 to 13 μg./g. tissue.
PROTECTION AGAINST SYSTEMIC POISONING BY MUSTARD GAS, DI(2‐CHLOROETHYL) SULPHIDE, BY SODIUM THIO‐SULPHATE AND THIOCIT IN THE ALBINO RAT
Authors: CALLAWAY S. , PEARCE K. A.
Published: July 2012

The lethal effects of mustard gas, di(2‐chloroethyl) sulphide, in the albino rat have been counteracted by Thiocit, a mixture of sodium thiosulphate and trisodium citrate in the ratio 10: 1, administered intraperitoneally in a dose of 2.75 g./kg. Thiocit afforded complete protection against greater than the median lethal dose of mustard gas whether given 10 min. before or 10 min. after mustard gas and raised the LD50 of mustard gas by approximately three times. The protection appeared whether the total dose of Thiocit was given in one injection or serially over 30 min. The effective doses of sodium thiosulphate and of Thiocit in rats were of the order of 3.0 g./kg. Sodium thiosulphate alone and Thiocit have been administered in single doses by slow infusion, by stomach tube and in drinking water. Both have shown activity by all routes of administration, but activity was greatest by intraperitoneal injection. The use of Thiocit in conjunction with mustard gas therapy is suggested.
THE EFFECT OF SOME OXIMES IN SARIN POISONING
Authors: RUTLAND J. P.
Published: July 2012

The effects of monoisonitrosoacetone (MINA), diacetylmonoxime (DAM) and pyridine‐2‐aldoxime methiodide (P2AM) upon the Cholinesterase of sarin poisoned rats have been studied. Monoisonitrosoacetone and diacetylmonoxime given before sarin protected blood and brain Cholinesterase from inhibition. Monoisonitrosoacetone given after the appearance of signs of poisoning caused a rapid reactivation of brain Cholinesterase. Diacetylmonoxime, at an equimolar dose, produced only a slight increase in enzyme activity, and pyridine‐2‐aldoxime methiodide, the best reactivator in vitro, reactivated blood but not brain Cholinesterase. There is a relationship between protection and reactivation of brain Cholinesterase and prevention and alleviation of signs of poisoning.
A METHOD FOR RECORDING PERISTALSIS IN ISOLATED INTESTINE
Authors: BÜLBRING EDITH , CREMA A. , SAXBY O. B.
Published: July 2012

A method is described for studying peristalsis in isolated pieces of guinea‐pig ileum. Records are obtained of longitudinal contractions, intraluminal pressure and volume of fluid expelled.
OBSERVATIONS CONCERNING THE ACTION OF 5‐HYDROXYTRYPTAMINE ON THE PERISTALTIC REFLEX
Authors: BÜLBRING EDITH , CREMA A.
Published: July 2012

In isolated guinea‐pig intestine 5‐hydroxytryptamine increased the longitudinal muscle contractions in response to acetylcholine while the ganglionic action of nicotine was first facilitated and then blocked. Phenyldiguanide, veratrine, veratridine and protoveratrine, like 5‐hydroxytryptamine, depressed the response to nicotine, leaving that to acetylcholine unaffected.

The sensory stimulants, like 5‐hydroxytryptamine, facilitated the peristaltic reflex when applied to the mucosa, and abolished it when applied to the serosa. Preceding the block, the initial effect of low concentrations of 5‐hydroxytryptamine applied to the serosa was a short stimulation of peristalsis.

Concentrations of 5‐hydroxytryptamine which had an approximately equal stimulant action (mucosal 1 to 4 × 10−6, serosal 2 to 8 × 10−8were tested when various parts of the reflex arc were blocked. During block by procaine introduced into the lumen, mucosal application of 5‐hydroxytryptamine re‐established peristalsis, but serosal application of 5‐hydroxytryptamine had no effect. During block by hexamethonium or atropine present in the bath, 5‐hydroxytryptamine restored peristalsis more effectively by serosal application than by mucosal application. During block by serosal application of 5‐hydroxytryptamine, morphine, phenoxybenzamine or dihydroergotamine, mucosal application of 5‐hydroxytryptamine restored the peristaltic reflex while serosal application had no effect. During block by 2‐bromo‐lysergic acid diethylamide or lysergic acid diethylamide acting from the serosal surface, 5‐hydroxytryptamine had no effect whether acting on the mucosal or on the serosal surface.

It is concluded that 5‐hydroxytryptamine facilitates the peristaltic reflex at two sites: when introduced into the lumen it stimulates mucosal sensory receptors; when acting from the serosal surface it sensitizes the muscle to the transmitter acetylcholine. There is also a transient stimulant action on the ganglia which is soon followed by inhibition; this indicates that 5‐hydroxytryptamine applied to the serosa abolishes peristalsis by ganglion block.
THE SCHISTOSOMICIDAL AND TOXIC EFFECTS OF SOME αω‐DI(p‐AMINOPHENOXY)ALKANES AND RELATED MONOAMINES
Authors: COLLINS R. F. , DAVIS M. , EDGE N. D. , HILL J.
Published: July 2012

An account is given of the results obtained with a number of p‐aminopbenoxyalkanes which were examined for activity against Schistosoma mansoni in mice and for the presence of retinotoxicity in cats. The first compound to be found active, 1: 5‐di(p‐aminophenoxy)‐pentane dihydrochloride (M & B 968A), was modified in a variety of ways in an attempt to increase its activity and to eliminate its ocular effects. It was found that a p‐aminophenoxyalkyl group was common to all the active compounds, but that the rest of the molecule could be any of several different groups, including alkoxy, phenoxy, and phenyl groups, without diminishing the activity. Although at least one p‐aminophenoxyalkyl group was essential for schistosomicidal activity, ocular toxicity was also shown by a p‐aminophenylalkyl derivative in which the ether linkage was absent.
THE TRYPANOCIDAL ACTIVITY OF SOME PYRIMIDYL‐AMINOPHENYLARSONIC COMPOUNDS
Authors: AINLEY A. D. , DAVEY D. G.
Published: July 2012

A series of substituted pyrimidylaminophenylarsonic acids have been prepared, reduced to the corresponding oxophenylarsines and finally, in certain cases, to the arsenobenzenes. The tervalent arsenicals were highly active against Trypanosoma rhodesiense in mice. 4‐(2:6‐Diaminopyrimid‐4‐ylamino)phenyloxoarsine either as the insoluble carbonate or the soluble isethionate was the most promising of these compounds.
THE EFFECT OF COOLING AND OF 5‐HYDROXYTRYPTAMINE ON THE PERISTALTIC REFLEX OF THE ISOLATED GUINEA‐PIG ILEUM
Authors: BELESLIN D. , VARAGIC V.
Published: July 2012

Cooling the guinea‐pig ileum to 19 to 26° abolished the emptying phase of the peristaltic reflex. The effects of cooling to 10° were usually reversible, but cooling to 5° for 3 to 8 hr. produced an irreversible decrease in or abolition of the emptying phase. 5‐Hydroxytryptamine (5‐HT) added in low concentrations to the fluid outside the intestine restored slight peristaltic activity after this activity had been abolished by cooling. If the peristalsis had been depressed but not abolished by cooling, 5‐HT in the bath sometimes abolished it. 5‐HT introduced into the lumen of the cooled gut regularly restored or increased peristaltic activity. This action was prevented by previous injection of 2‐bromolysergic acid diethylamide into the lumen. It is suggested that, when introduced into the lumen, 5‐HT may sensitize the sensory receptors in the mucosa of the cooled intestine. When applied outside, 5‐HT may facilitate transmission at synapses involved in the peristaltic reflex arc, the excitability of which has been depressed by cooling.
THE ACTIVITY OF A VARIETY OF CHEMICAL COMPOUNDS AGAINST EXPERIMENTAL TETANUS
Authors: LAURENCE D. R. , WEBSTER R. A.
Published: July 2012

A range of chemical compounds, mostly with central nervous system depressant activity, have been tested against experimental tetanus in the rabbit. A number of the more potent tested, including mephenesin, betanaphthoxyethanol, barbiturates and phenothiazine derivatives, have been accurately assayed by a method of quantitative electromyography. Phenothiazine derivatives were found to be the most potent anticonvulsants and of these acetylpromazine had the greatest activity. The difficulties of direct comparison of the potency of substances from different chemical groups is discussed.
PHARMACOLOGICAL PROPERTIES OF PEMPIDINE (1:2:2: 6: 6‐PENTAMETHYLPIPERIDINE), A NEW GANGLION‐BLOCKING COMPOUND
Authors: CORNE S. J. , EDGE N. D.
Published: July 2012

Pempidine (1: 2: 2: 6: 6‐pentamethylpiperidine) is a long‐acting ganglion‐blocking compound which is effective by mouth. By intravenous injection it has a similar potency to hexamethonium on the preganglionically stimulated nictitating membrane of the cat. The compound blocks the effects of intravenous nicotine and of peripheral vagal stimulation on the blood pressure; it also causes dilatation of the pupil after removal of the sympathetic innervation. On the guinea‐pig ileum, the predominant effect of the compound is to inhibit nicotine contractions. Pempidine is well absorbed from the gastro‐intestinal tract as judged by (a) the low ratio (6.9) of oral to intravenous toxicities, (b) the rapid development of mydriasis in mice after oral administration of small doses, and (c) the rapid onset of hypotension when the compound is injected directly into the duodenum of anaesthetized cats. Other actions include neuromuscular paralysis of curare‐like type when large doses of the compound are injected intravenously and central effects such as tremors which occur with near toxic doses. In cats with a low blood pressure, large intravenous doses have a slight pressor action.
THE FATE OF OXYTOCIN IN MALE AND FEMALE RATS
Authors: GINSBURG M. , SMITH M. W.
Published: July 2012

A method for quantitative extraction of oxytocin from blood is described. The disappearance of injected oxytocin from the circulation in rats was shown to depend upon its uptake in the kidneys and in organs of the splanchnic vascular area. In lactating rats there was uptake by an additional organ or tissue, probably the mammary gland. In animals without kidneys or lactating mammary glands and with no circulation in the splanchnic area oxytocin was distributed into a volume greater than the extracellular fluid volume, and after equilibration the concentration in plasma did not change significantly. During severe haemorrhage increased amounts of antidiuretic activity were detected in blood when there was no significant increase in oxytocic activity.
THE PHARMACOLOGY OF THE ETHANESULPHONATE ANION
Authors: GOODFORD P. J. , ING H. R.
Published: July 2012

A method of preparing analytically pure sodium ethanesulphonate, C2H5SO3Na.H2O, in quantity is described. Physiological saline solutions were prepared in which a proportion of the sodium chloride normally present was replaced by an equimolar concentration of sodium ethanesulphonate. The effects of partial or total replacement of sodium chloride were examined upon a series of isolated organs, and the guinea‐pig ileum preparation was found to be particularly sensitive to the change. Evidence is presented that these low‐chloride solutions depolarized the cell membrane of smooth muscle, and that this effect might have been due to an alteration of the chloride ion potential.
MECHANISM OF ACTION OF ORAL ANTI‐DIABETIC DRUGS
Authors: AIMAN RANITA , CHAUDHARY NIRMALA
Published: July 2012

The fall in blood sugar with carbutamide (BZ55) 24 hr. after the maintenance dose of insulin (28.1% ± 2.9 s.e.) in rabbits made severely diabetic with alloxan was significantly different from the change in the blood sugar with the same drug given 72 hr. (6.8% ± 2.0) or distilled water given 24 hr. (7.7% ± 1.3) respectively after the last dose of insulin. It is postulated that the drug acts by liberating bound insulin in the plasma.
THE ACTION OF NITROPHENOLS ON THE PULMONARY VENTILATION OF RATS
Authors: GRANT C. M.
Published: July 2012

The ventilatory effects of the three mononitrophenols and six dinitrophenols have been examined in anaesthetized rats. The minute volume of ventilation increased in all the test groups, the increase reaching the 99% significance level with seven compounds (P<0.01), the 95% level with 3‐nitrophenol (P<0.05), and the 90% level with 3,5‐dinitrophenol (P<0.10). The effects of 4‐nitrophenol, 3,4‐dinitrophenol, 3‐nitrophenol, and 2,5‐dinitrophenol, in increasing carbon dioxide output relative to oxygen consumption, are not explicable on the basis of simple hyperventilation, and are attributed to a metabolic effect at the cellular level. The potency of the nitrophenols in stimulating respiration is related to their structure, nitro groups being most effective in the ortho position and least effective in the meta position, and 2,4‐dinitrophenol being the most powerful respiratory stimulant of the group. 2,6‐Dinitrophenol does not conform to this generalization; one unique feature of its structure is indicated, as a possible explanation for the discrepancy. The gradation of potency of the nitrophenols (except 2,6‐dinitrophenol) parallels the gradation of acidic properties in the group; the more strongly acid compounds stimulate respiration more powerfully. This is not a direct effect on blood pH, since the compounds were administered in neutral or slightly alkaline solution. Methaemoglobin formation was found to occur with 2,5‐dinitrophenol, and to a smaller inconstant extent with three other compounds. Further work is suggested, to explore whether peripheral‐acting ventilatory stimulation by 2,4‐dinitrophenol is necessarily associated with peripheral metabolic enhancement, or whether the two effects can be dissociated.
A METHOD FOR MEASURING THE ACTIVITY OF COMPOUNDS WITH AN ACTIVITY LIKE VITAMIN K AGAINST INDIRECT ANTICOAGULANTS IN RATS
Authors: LOWENTHAL J. , TAYLOR J. D.
Published: July 2012

A method for the estimation of the activity of compounds like vitamin K using rats treated with an indirect anticoagulant is described. The assay measured the speed of onset and magnitude of the antidotal effect. Under the conditions employed, only vitamin K1 produced a significant response. Vitamin K3 and its water‐soluble derivatives were inactive. Both the magnitude and the speed of onset of the antidotal effect of vitamin K1 were found to depend on the extent to which it was in solution. The assay gave results of fair accuracy and reproducibility, which permitted a full statistical analysis and provided an estimate of error.
THE EFFECTS OF RESERPINE AND OTHER AGENTS UPON LEPTAZOL CONVULSIONS IN MICE
Authors: LESSIN A. W. , PARKES M. W.
Published: July 2012

Reserpine and tetrabenazine reduced the survival time of mice infused with leptazol. This effect was antagonized by pretreatment with iproniazid. The survival time of iproniazid‐treated mice was prolonged by 5‐hydroxytryptophan but not by 3:4‐dihydroxyphenylalanine. These findings suggest a relation between leptazol sensitivity and brain levels of 5‐hydroxytryptamine.
DRUG RESISTANCE IN TRYPANOSOMES; CROSS‐RESISTANCE ANALYSES
Authors: WILLIAMSON J. , ROLLO I. M.
Published: July 2012

Eight strains of Trypanosoma rhodesiense, made resistant respectively to atoxyl, butarsen, acriflavine, stilbamidine, Surfen C, suramin, and pontamine sky blue 5BX, have been examined for cross‐resistance to representatives of nine structurally dissimilar groups of trypanocide. On the basis of their predominant ionic form at blood pH, these groups are considered in three main classes: (a) feebly ionized (neutral aromatic arsenicals), (b) ionized as cations (melaminyl arsenicals and antimonials, acridine derivatives, diguanidines and diamidines, 6‐aminoquinoline and 6‐aminocinnoline derivatives, phenanthridinium derivatives, triphenylmethane dyes), and (c) ionized as anions (carboxylated aromatic arsenicals and sulphonated naphthylamine derivatives). The results are discussed in relation to those of other workers and to possible modes of trypanocidal drug action. Cross‐resistance behaviour is not wholly explicable on an ionic basis; the results suggest that stereospecific structural changes associated with initial drug uptake occur in resistant trypanosomes.
THE SCHISTOSOMICIDAL AND TOXIC EFFECTS OF SOME N‐p‐AMINOPHENOXYALKYLAMIDES
Authors: COLLINS R. F. , DAVIS M. , EDGE N. D. , HILL J. , READING H. W. , TURNBULL ELEANOR R.
Published: July 2012

Several N‐(ω‐p‐aminophenoxyalkyl)amides were active against Schistosoma mansoni in mice. One of the most effective, N‐(5‐p‐aminophenoxypentyl)benzamide (M&B3002), acted more rapidly than lucanthone on adult worms but less rapidly than antimony potassium tartrate. It was inactive against immature worms. This compound and M&B2948A (N‐(5‐p‐aminophenoxypentyl)phthalimide) were both active against S. mansoni in hamsters. In monkeys M&B2948A was inactive, whilst M&B3002 was not tested for therapeutic activity. Several of the compounds were examined for the production of visual impairment in cats. Although this property was not entirely absent, its incidence was very much lower in this amide series than among other ω‐p‐aminophenoxyalkyl derivatives not containing an amide group. M&B3002 and M&B2948A produced impairment of vision in only a small proportion of the large number of cats tested. The general toxicology of the two drugs was studied in several species, and also their absorption and excretion in mice and rats; this was to provide information for a clinical trial.
THE EFFECT OF PIPERAZINE ON SUCCINATE PRODUCTION BY ASCARIS LUMBRICOIDES
Authors: BUEDING E. , SAZ H. J. , FARROW G. W.
Published: July 2012

Piperazine reduced the production of succinate by Ascaris lumbricoides. This effect was reversible. There was a close parallelism between the concentrations of piperazine which paralysed the worm and those which inhibited the formation of succinate. Piperazine did not affect the incorporation of [2‐14C]lactate into succinate by strips of Ascaris muscle. It was concluded that production of succinate supplies energy for the contraction of Ascaris muscle.
INCREASE OF 5‐HYDROXYTRYPTAMINE IN THE RAT BRAIN BY RAUNESCINE
Authors: PAASONEN M. K. , KÄRKI N. T.
Published: July 2012

The Rauwolfia alkaloid raunescine (5 mg./kg., intraperitoneally) increased the concentration of 5‐hydroxytryptamine in the brains of rats after iproniazid pre‐treatment. This was evident 3 to 4 hr. after raunescine administration. There was no general increase in the noradrenaline content of the brains. In the intestine, raunescine depleted the 5‐hydroxytryptamine content by about 50% within 3 to 4 hr. if the animals had been pre‐treated with iproniazid. Iproniazid did not increase the content of noradrenaline in the intestine.
OXIMES OF αω‐DIQUATERNARY ALKANE SALTS AS ANTIDOTES TO ORGANOPHOSPHATE ANTICHOLINESTERASES
Authors: BERRY W. K. , DAVIES D. R. , GREEN A. L.
Published: July 2012

Sixteen compounds of the general structure {HON: CH.C3H4N+.[CH2]n.R+}2Br− have been synthesized in which the position of the oxime group in the pyridine ring, the second charged group R+ and the number of methylene groups between the charged atoms have been varied. The rate at which these compounds reactivate Cholinesterase inhibited by ethyl pyrophosphate has been studied and a number have been found which are more active than 2‐hydroxyiminomethyl‐N‐methylpyridinium methanesulphonate. Since considerable variation in structure was found among those compounds which are better reactivators than the latter, the concept that 2‐hydroxyiminomethyl‐N‐methylpyridinium salts are unique in their ability to fit the surface of the inhibited enzyme is no longer tenable. The reactivating power of these oximes correlated well with their ability, when given in conjunction with atropine, to save the lives of mice poisoned by ethyl pyrophosphate. The most effective compounds, NN′‐trimethylenebis‐(4‐hydroxyiminomethylpyridinium bromide) and NN′‐hexamethylenebis(2‐hydroxyiminomethylpyridinium bromide), contained a further oxime group in R+, but the second oxime group was not essential for high activity. These new oximes were also superior in saving the lives of mice poisoned with sarin (isopropyl methylphosphonofluoridate), but the improvement was not as dramatic as when the mice were poisoned with ethyl pyrophosphate. The toxicity of the compounds varied with both n and R+ and was unrelated to the therapeutic potency.
SUPERSENSITIVITY DUE TO PROLONGED ADMINISTRATION OF GANGLION‐BLOCKING COMPOUNDS
Authors: EMMELIN N.
Published: July 2012

Repeated subcutaneous injections of ganglionic blocking agents in cats were found to cause a supersensitivity towards adrenaline in the submaxillary gland and the nictitating membrane. The supersensitivity resembled that produced by preganglionic denervation, namely section of the chorda tympani in the case of the gland and of the cervical sympathetic trunk in the case of the membrane. The blocking compounds used were chlorisondamine chloride and hexamethonium. With the former, the sensitization could be obtained in the normally innervated structures. When hexamethonium was used, however, the effect on the gland could be produced only if the synapse had been made particularly susceptible to the blocking action of this agent; this was achieved by cross‐suture experiments.
CENTRAL EFFECTS PRODUCED BY INJECTION OF 48/80 INTO THE CEREBRAL VENTRICLES OF MICE
Authors: ROCHA E SILVA M.
Published: July 2012

Injections of 20 to 30 μg. of 48/80 into the cerebral ventricular spaces of mice produced a condition of motor excitement termed “delirium ambulatorium.” This condition was aggravated by previous intraperitoneal injection of tranquillizers, atropine, and promethazine, not affected by previous injection of mepyramine and abolished by a previous injection of pentobarbitone. When an intraperitoneal injection of strychnine was followed by an intraventricular injection of 48/80, the strychnine convulsions became more violent, but the pattern of delirium ambulatorium was not produced.
ACTIONS OF SOME ANALOGUES OF 5‐HYDROXYTRYPTAMINE ON THE ISOLATED RAT UTERUS AND THE RAT FUNDUS STRIP PREPARATIONS
Authors: BARLOW R. B. , KHAN I.
Published: July 2012

The search for substances which antagonize 5‐hydroxytryptamine, and for those which act like it, has been extended to cover 5‐substituted indoles which are analogues of 5‐hydroxytryptamine, rather than analogues of tryptamine like the compounds previously studied by us. The isolated rat uterus and rat fundus strip preparations have been used to determine activity. The relationships between structure and activity of the compounds studied were not the same on the two preparations nor were they the same from one homologous series to another. These differences may be partly explained by the presence of amine oxidase in the rat fundus, as Vane (1959) has suggested, and by supposing that it is absent from the rat uterus. None of the compounds had marked antagonist activity. The most active antagonist on the rat uterus was 3‐(2‐aminopropyl)‐5‐benzyloxyindole, but this was less potent than 5‐benzyloxygramine. On the rat fundus strip, however, the only antagonist, 5‐benzyloxy‐3‐(2‐dimethylaminoethyl)indole, was more active than 5‐benzyloxygramine. On both preparations the most active stimulant was 3‐(2‐aminopropyl)‐5‐hydroxyindole, which was about half as potent as 5‐hydroxytryptamine. The next most active were 3‐(2‐aminopropyl)‐5‐methoxyindole and bufotenine.
THE EFFECT OF DIET ON THE 5‐HYDROXYTRYPTAMINE CONTENT OF THE SMALL INTESTINE AND OTHER ORGANS IN RATS AND MICE
Authors: SULLIVAN T. J.
Published: July 2012

In rats, a diet of meat or liver caused a rise in the amount of 5‐hydroxytryptamine in the small intestine, an increase in the weight of the intestine and a 10‐fold increase in anaerobic bacteria in the rectum. A diet containing added tryptophan did not affect tissue levels of 5‐hydroxytryptamine in rats, but in mice there was a rise of 5‐hydroxytryptamine in various tissues. The significance of these findings is discussed together with the possible role of intestinal bacteria in mediating the effects caused by a meat diet. No change was observed in the 5‐hydroxytryptamine content of brain or in the distribution of argentaffin cells in the jejunum as a result of these diets.
THE DISTRIBUTION OF 5‐HYDROXYTRYPTAMINE AND ADENOSINETRIPHOSPHATE IN CYTOPLASMIC PARTICLES OF THE DOG'S SMALL INTESTINE
Authors: PRUSOFF W. H.
Published: July 2012

The distribution of 5‐hydroxytryptamine, adenosinetriphosphate, and succinic dehydrogenase in sucrose homogenates of the dog's small intestine has been studied. The adenosinetriphosphate was present in two different layers which could be separated by density gradient centrifugation. The upper layer contained also much succinic dehydrogenase, but no amine; it is probably composed of mitochondria. The lower layer contained not only adenosinetriphosphate but also the major portion of the particle‐held 5‐hydroxytryptamine. The mean molar ratio, amine: adenosinetriphosphate, in the lower layer was 2.6. The experiments suggest that adenosinetriphosphate in the intestine is of importance in the storage of 5‐hydroxytryptamine, resembling the function of adenosinetriphosphate in the storage of the catechol amines of the adrenal medulla.
THE EFFECTS OF CORTICOSTEROIDS AND RELATED COMPOUNDS ON THE HISTAMINE AND 5‐HYDROXYTRYPTAMINE CONTENT OF RAT TISSUES
Authors: TELFORD J. M. , WEST G. B.
Published: July 2012

Daily intramuscular injections of cortisone, prednisolone, triamcinolone, dexamethasone, fludrocortisone and 2‐methylfludrocortisone markedly reduced the histamine and 5‐hydroxytryptamine contents of the skin and small intestine of rats; there was an increase, however, in the amine contents of the stomach. The sex hormones were weaker in these effects while deoxycortone and corticotrophin were inactive. When the skin was depleted of half of its 5‐hydroxytryptamine by prolonged treatment with polymyxin B, the rate of recovery of this amine was retarded by the glucocorticoids. The glucocorticoid activity of a steroid and its ability to produce changes in the histamine and 5‐hydroxytryptamine contents of tissues are related.
EVALUATION OF ANTAGONISTS OF HISTAMINE, 5‐HYDROXYTRYPTAMINE AND ACETYLCHOLINE IN THE GUINEA‐PIG
Authors: HOLGATE J. A. , WARNER B. T.
Published: July 2012

Changes in the resistance to entry of air into the lungs of anaesthetized guinea‐pigs have been used to study the effects of histamine, 5‐hydroxytryptamine, and acetylcholine. Some known antagonists of these bronchoconstrictor agents have been investigated. The degree of antagonism has been expressed in terms of the dose ratio, previously used only with in vitro preparations.
TREMOR IN CATS: THE EFFECT OF ADMINISTRATION OF DRUGS INTO THE CEREBRAL VENTRICLES
Authors: DOMER F. R. , FELDBERG W.
Published: July 2012

In cats, tremor produced by intraperitoneal pentobarbitone sodium or by intramuscular chlorpromazine was abolished by injection into the cerebral ventricles of a few gamma of adrenaline or noradrenaline, but not of other sympathomimetic amines or of anti‐Parkinsonian drugs. Chloralose, urethane, calcium chloride, and magnesium chloride produced anti‐tremor activity when administered in this way. When adrenaline or noradrenaline was perfused from a lateral ventricle to the aqueduct during pentobarbitone sodium tremor, tremor was inhibited when less than 1 μg. had been perfused. Adrenaline was at least four times as active as noradrenaline. Isoprenaline inhibited tremor when perfused in higher concentrations, but perfusion of ephedrine, amphetamine or of the anti‐Parkinsonian drugs in high concentrations was ineffective. Perfusion of 2 μg. of chloralose or of 20 μg. of calcium chloride was sufficient to inhibit tremor. Intraventricular injections of 250 to 500 μg. of 5‐hydroxytryptamine initiated tremor. Possible physiological implications of these findings are discussed.
THE EFFECT OF IPRONIAZID AND IMIPRAMINE ON THE BLOOD PLATELET 5‐HYDROXYTRYPTAMINE LEVEL IN MAN
Authors: MARSHALL ELIZABETH F. , STIRLING G. S. , TAIT A. C. , TODRICK A.
Published: July 2012

Observations are reported on the blood platelet 5‐hydroxytryptamine content of six patients receiving imipramine, N‐(γ‐dimethylaminopropyl)‐iminodibenzyl hydrochloride. The response was a fall to a level of one‐sixth of the original in three weeks, with little change thereafter. This is in sharp contrast to the action of iproniazid which caused a rise of some 200% in the blood platelet 5‐hydroxytryptamine level over the same period. Imipramine in a concentration of 1 mg./ml. had no inhibitory action on 5‐hydroxytryptophan decarboxylase; 8·0 μg./ml. of imipramine suppressed two‐thirds of the in vitro uptake of 5‐hydroxytryptamine (2·5 μg./ml.) by normal human platelets.
THE NEUROMUSCULAR BLOCKING PROPERTIES OF A SERIES OF BIS‐QUATERNARY TROPEÏNES
Authors: HAINING C. G. , JOHNSTON R. G. , SMITH J. M.
Published: July 2012

Linkage of two tropine esters through their nitrogen atoms by the chain ‐[CH2]m‐O‐CO‐[CH2]n‐CO‐O‐[CH2]m‐, in which m was 2 or 3 and n varied from 0 to 6, gave compounds which produced neuromuscular block without depolarization. Reversibility by neostigmine was confirmed for a few compounds. Potency was found to depend upon the tropine ester employed and upon the values of n and m. Short duration and hypotensive properties were favoured by the higher values of n. The duration of action of the compound based on the phenylacetic acid ester of tropine, in which n = 4 and m = 2, varied considerably in different species. Epimerization, in which the relative positions of the methyl group and the linking chain on the quaternary tropane nitrogen atom were reversed, did not produce substances having more favourable properties than those possessed by the unepimerized compounds.
THE QUANTITATIVE ASSAY OF CORTICOTROPHIN USING RATS TREATED WITH HYDROCORTISONE ACETATE
Authors: DEKANSKI J. B. , HARVIE MARGARET I.
Published: July 2012

An attempt has been made to modify the Sayers method for the assay of corticotrophin by substituting for hypophysectomy an injection of sufficient hydrocortisone acetate to suppress the release of endogenous pituitary corticotrophin in intact rats over the period of the assay. The results of forty such assays of subcutaneous corticotrophin seem to indicate that this procedure is about 1 1/2 to 2 times as efficient as the original method using hypophysectomized rats. For a 2 + 2 point assay it was necessary to use a minimum of twenty‐four to thirty‐two rats.
THE GANGLION‐BLOCKING ACTIVITY OF AMINOBICYCLO‐[2,2, 1]HEPTANES (CONGENERS OF MECAMYLAMINE) AND BICYCLO[3,2, 1]AZAOCTANES (BRIDGED CONGENERS OF PEMPIDINE)
Authors: EDGE N. D. , CORNE S. J. , LEE G. E. , WRAGG W. R.
Published: July 2012

The structural requirements for strong ganglion‐blocking activity and long duration of action amongst some lower homologues of mecamylamine, together with the discovery of similar activities amongst isomers with enlarged ring structures, are described. In both series of compounds it was found that the successive introduction of C‐methyl groups surrounding the nitrogen atom resulted in a progressive increase in ganglion‐blocking activity and duration of action.
APOMORPHINE‐INDUCED PECKING IN PIGEONS
Authors: DHAWAN B. N. , SAXENA P. N.
Published: July 2012

Apomorphine produced persistent pecking in pigeons, the latent period, intensity and duration of which were related to the dose. The ED50 was estimated as 78.1±11.1 μg./kg. On chronic administration of apomorphine there was a significant decrease in latent period and weight which quickly returned to normal on stopping the drug. No conditioning and no tolerance were observed. The uncertain emetic effect of apomorphine in pigeons has been confirmed. Ten other centrally acting agents tested (caffeine, cocaine, 5‐hydroxytryptamine, lysergic acid diethylamide, methamphetamine, morphine, nalorphine, pentylenetetrazol, strychnine, and yohimbine) failed to produce similar effects in pigeons.
PHARMACOLOGICAL STUDY OF A NEW ANTIBIOTIC OF BACILLARY ORIGIN
Authors: BERGMANN FELIX , REITLER R. , CHAIMOVITZ M. , BERGMANN DAVID
Published: July 2012

The purified extract of a new bacterial mutant, which exhibits antibiotic activity against paramecia and amoebae, was tested on various smooth muscle preparations. Spontaneous activity as well as the response to a variety of smooth muscle stimulants was diminished or completely suppressed. Intravenous injection of the extract lowered the blood pressure of the anaesthetized cat or dog. These properties may explain the beneficial effect of the extract on the intestinal symptoms of human amoebiasis, before eradication of the parasites.
THE INHIBITION OF MAST CELL DAMAGE AND HISTAMINE RELEASE IN ANAPHYLAXIS BY PYRIDINE AND DIPHOSPHOPYRIDINE NUCLEOTIDASE INHIBITORS. COMPARISON WITH COMPOUND 48/80
Authors: MOTA IVAN , DA SILVA W. DIAS , FERNANDES J. FERREIRA
Published: July 2012

In rats and guinea‐pigs both mast cell damage and histamine release in anaphylaxis were inhibited by pyridine, nicotinamide, diethylnicotinamide, nicotinic acid, isonicotinic acid and isonicotinic acid hydrazide, which are known to be inhibitors of diphosphopyridine nucleotidases. On the other hand these compounds potentiated histamine release and mast cell damage by compound 48/80 in guinea‐pigs although inhibiting the same phenomena in rats. The relationship of these findings with the mechanism of histamine liberation in anaphylaxis is discussed.
MAXIMAL INHIBITION OF CHOLINESTERASE IN THE CENTRAL NERVOUS SYSTEM
Authors: SCHAUMANN W.
Published: July 2012

In experiments on mice treated with pralidoxime iodide (pyridine‐2‐aldoxime methiodide; PAM) and atropine, the cholinesterase activity in the brain was assayed after poisoning with very high doses of organophosphorous anticholinesterases. Acetylcholine was added to the buffer solution in which the brains were homogenized. This precaution reduced the combination between free inhibitor present in the tissue and active enzyme, and the cholinesterase activity found was below 0.5% of controls. When the experimental data were corrected for spontaneous reactivation in vitro during incubation, the calculated activities in vivo were even less. It is concluded that mice can survive complete inactivation of the cholinesterase in the central nervous system, if enough atropine is given to protect the animals against the toxic effects of the accumulating acetylcholine.
THE ANTAGONISM OF MUSCLE RELAXANTS AMBENONIUM AND METHOXYAMBENONIUM IN THE CAT
Authors: BLABER L. C.
Published: July 2012

The ability of ambenonium and a methoxy analogue to antagonize paralysis produced either by tubocurarine or by decamethonium has been studied in the tibialis anterior muscle of the cat under chloralose anaesthesia. In small doses, both oxamides facilitated neuromuscular transmission, but in larger doses they depressed the sensitivity of the motor end plates to depolarizing substances and it is considered that this latter action is sufficient to account for their anti‐decamethonium action. Although both compounds possess anticholinesterase activity, there was found to be no correlation between their relative abilities to antagonize tubocurarine paralysis and their abilities to inhibit muscle cholinesterase in vitro.
SOME PHARMACOLOGICAL PROPERTIES OF o‐METHYL‐α‐PROPYLAMINOPROPIONANILIDE, A NEW LOCAL ANAESTHETIC
Authors: ÅSTRÖM A. , PERSSON N. H.
Published: July 2012

The anaesthetic action of o‐methyl‐α‐propylaminopropionanilide (L 67, Astra) has been studied and compared with lignocaine in different in vitro and in vivo tests. Procaine and amethocaine (tetracaine) were also included in several of the comparisons. In nerve block on the isolated frog sciatic nerve L 67 is somewhat less effective than lignocaine. In all in vivo conditions, however, L 67 is quite comparable to lignocaine as to duration, latency and frequency of anaesthesia. As a spinal anaesthetic in rabbits 2 to 4% solutions of L 67 give a longer duration of anaesthesia than lignocaine. Toxicity in mice and rabbits and respiratory and circulatory effects in cats have also been evaluated. L 67 is almost twice as well tolerated as lignocaine. It is concluded that L 67 may prove to be a useful anaesthetic in certain clinical applications.