bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of central stimulant drugs on acetylcholine release from rat cerebral cortex
Authors: HEMSWORTH B. A. , NEAL M. J. 
Published: July 2012

. The effects of central stimulant drugs injected intraperitoneally were examined on the release of acetylcholine (ACh) from the cerebral cortex of the anaesthetized rat. The effects of the drugs in increasing ACh release were approximately parallel to the increases produced in the electrical activity of the brain.
. Leptazol in a dose of 150 mg/kg increased the release of ACh by 2.9 times the resting release and in a dose of 300 mg/kg by 7.5 times; on the e.e.g. the injection produced a large increase in the electrical activity.
. Picrotoxin in a dose of 12 mg/kg increased the release of ACh by 7.5 times and on the e.e.g. caused a large increase in activity.
. Strychnine in doses of 8 mg/kg and 12 mg/kg increased the release of ACh by 2.0 and 2.4 times and produced a small increase in the activity of the e.e.g.
. Dexamphetamine in a dose of 100 mg/kg increased the release of ACh by 1.9 times and had no appreciable effect on the e.e.g.
. Nikethamide in a dose of 2 g/kg increased the release of ACh by 2.3 times and produced no appreciable change in the e.e.g.
. Caffeine in a dose of 100 mg/kg produced no significant effect on the release of ACh.
Further studies on the histidine‐histamine relationship in vivo: effects of endotoxin and of histidine decarboxylase inhibitors
Authors: REILLY MARGARET A. , SCHAYER R. W. 
Published: July 2012

. Mice were injected with (14C)‐l‐histidine, killed at various intervals, and tissues assayed for (14C)‐histamine. In some cases free (14C)‐l‐histidine and total (14C) were also determined.
. Removal of stomach, the most active histamine‐forming tissue, failed to reduce the (14C)‐histamine content of any tested tissue; (14C)‐histamine concentrations in lung and muscle of gastrectomized mice were higher than in sham‐operated controls.
. In mice pretreated with endotoxin and subsequently injected with (14C)‐l‐histidine, the (14C)‐histamine content of liver, lung and muscle was markedly higher than in controls. The increased concentrations of (14C)‐histamine in endotoxin‐pretreated mice seemed to reflect a greater rate of formation; they could be attributed neither to changes in tissue concentration of (14C)‐l‐histidine, to increased uptake from other tissues, nor to impaired ability to inactivate histamine.
. Results of studies on in vivo effectiveness of several histidine decarboxylase inhibitors are reported.
. The following conclusions are supported by the evidence presented: (a) in stressed mice, those tissues which show activation of histidine decarboxylase also show increased ability to form histamine in vivo; (b) tissue histamine is largely formed locally; (c) histidine decarboxylase inhibitors are highly effective in blocking histamine formation in mast cells and in stomach, but do not normally reach the locus of an inducible form of histidine decarboxylase; (d) the inducible form of histidine decarboxylase in liver may be located in phagocytic microvascular endothelial cells; (e) in conditions favouring near‐maximal activation of histidine decarboxylase, the histamine‐methylating enzyme of liver and diamine oxidase of intestine showed no inducible characteristics; (f) blood histamine concentrations do not accurately reflect changes in tissue histamine formation.
The binding of 3H‐digitoxigenin by guinea‐pig atrial tissue
Authors: KUSCHINSKY K. , LÜLLMANN H. , van ZWIETEN P. A. 
Published: July 2012

. The uptake and release of 3H‐digitoxigenin by electrically driven, guinea‐pig isolated atria (frequency 180/min) has been determined for two different medium concentrations of the genin. Both concentrations—1 × 10−7 and 5 × 10−7 g/ml.—caused a pronounced increase in contractile force.
. The uptake of 3H‐digitoxigenin reached equilibrium after approximately 2 hr of incubation. At equilibrium, the tissue/medium radioactivity ratio reached a value of about 8 for both concentrations studied. After initial saturation of the atria with 3H‐digitoxigenin, approximately 60% of the accumulated genin was released on wash‐out in genin‐free Tyrode solution for 2 hr.
. After presaturation of the atria with equimolar concentrations of either digitoxigenin or digitoxin (both non‐radioactive) the uptake of 3H‐digitoxigenin occurred more slowly. After 2 hr of incubation approximately 60–70% of the tissue bound digitoxigenin or digitoxin had exchanged against 3H‐digitoxigenin from the medium. Presaturation of the atria with ouabain in equimolar concentration did not significantly affect the uptake of 3H‐digitoxigenin.
. The release process of 3H‐digitoxigenin was not affected by the same concentration of non‐radioactive digitoxigenin as used for the accumulation of the genin.
. The kinetic properties of 3H‐digitoxigenin, determined by means of isotope techniques, are very similar to those of 3H‐digitoxin. The discrepancy between kinetic and pharmacological behaviour is, however, much larger for digitoxigenin than for digitoxin. Obviously, the presence or absence of the sugar moieties considerably influences the behaviour of the molecule towards the specific receptors, without particularly affecting the binding to unspecific, cellular structures.
Interaction between desipramine, tyramine, and amphetamine at adrenergic neurones
Authors: BRODIE B. B. , COSTA E. , GROPPETTI A. , MATSUMOTO C. 
Published: July 2012

. Small doses of tyramine (10 μg/kg intravenously) are taken up by rat heart, which can concentrate the amine 7.3‐fold over the plasma level.
. Desipramine (DMI) blocks the uptake of small doses of tyramine by rat heart, but in doses of 20 mg/kg intraperitoneally, it does not affect the cardiac concentrations of tyramine following 20 mg/kg intramuscularly of the drug. The same dose of DMI prevents the depletion of noradrenaline (NA) elicited by intramuscular injection of tyramine 20 mg/kg.
. DMI prevents the depletion of heart NA elicited by (+)‐amphetamine 5 mg/kg given intraperitoneally to demedullated rats and enhances the heart concentration of amphetamine.
. Liposoluble amphetamine enters sympathetic nerves by simple diffusion. It is suggested that DMI prevents the release of heart NA caused by this indirect sympathomimetic through an action within the adrenergic neurone.
The pharmacological properties of fibrinogen degradation products
Authors: BULUK KAROL , MAŁOFIEJEW MICHAŁ 
Published: July 2012

A method of obtaining partially purified products of plasmin degradation of fibrinogen (F.D.P.) is described. The F.D.P. passes through dialysing tubes and does not lose its activity during heating for 15 min at a temperature of 56° C.
In experiments on isolated organs, F.D.P. in small doses potentiates the contractile action of bradykinin, kallidin, angiotensin, histamine, 5‐hydroxytryptamine, acetylcholine, adrenaline and noradrenaline. In high concentrations, F.D.P. induces an increase in initial tonus of the smooth muscles and simultaneously lowers the sensitivity of the smooth muscles to the action of the pharmacologically active substances mentioned.
A similarity in the effect of different concentrations of KC1 and different concentrations of F.D.P. on the contractile reaction of the guinea‐pig intestine to constant doses of histamine and bradykinin and on the initial tonus of the smooth muscles is observed.
A hypothesis is presented that F.D.P. in small doses potentiates the contractile action of amines and polypeptides on the smooth muscles and in larger doses increases the initial tonus of these muscles by changing the concentration of the cell electrolytes.
Influence of rat plasma and of various cations on the anti‐eledoisin activity of morin
Authors: GASCON A. L. 
Published: July 2012

The musculotropic activity of eledoisin on the isolated guinea‐pig ileum is antagonized by morin, a flavonoid derivative.
The anti‐eledoisin activity of morin is abolished by fresh rat plasma and by deproteinized rat plasma, but not by deionized plasma.
Cupric acetate can restore the inhibitory property of the deionized plasma and can also inactivate morin.
This effect of rat plasma and of cupric acetate is inhibited by (–)‐penicillamine and by N‐acetyl‐(±)‐penicillamine.
It is concluded that, when in contact with rat plasma, morin is probably inactivated as a consequence of the formation of a complex with the plasma copper.
The time course of action of (—)‐hyoscine after intramuscular injection
Authors: BRAND J. J. 
Published: July 2012

Although (–)‐hyoscine has been in clinical use for many years, there is little detailed information concerning the speed of absorption or duration of action of the drug after single intramuscular doses.
The time course of action of the drug was therefore examined using biological methods, and measurements were made of saliva flow, pulse rate, pupil diameter and mental alertness for up to 8 hr after doses of 0.4, 0.2, 0.1 and 0.05 mg of the hydrobromide.
These techniques gave comparable results and peak activity was achieved at 1–2 hr after dose and followed by a gradual decline over the 8 hr period.
The results are compared with those of earlier experiments of a similar kind, and discussed in relation to their bearing on both therapeutics and experimental design.
Displacement from protein binding of sulphormethoxine by phenylbutazone using in vivo dialysis in rats
Authors: McQUEEN E. G. 
Published: July 2012

Displacement of the ultra‐long‐acting sulphonamide sulphormethoxine from binding to serum proteins by phenylbutazone has been demonstrated by in vivo dialysis in rats. The technique used involved the introduction of dialysis sacs into the peritoneal cavity. The regression line relating free to total sulphormethoxine was significantly displaced after addition of phenylbutazone to the regime although the mean level of free drug was not significantly raised. No significant effect was observed on the proportion of phenylbutazone in the free form. The range of concentrations employed corresponded to that encountered clinically.
In vitro experiments with comparable concentrations of both drugs confirmed displacement of sulphormethoxine by phenylbutazone. Insignificant displacement of phenylbutazone from binding occurred. These experiments indicated the relationships between the relative affinities of sulphormethoxine and phenylbutazone for serum proteins and the extent to which mutual displacement from binding occurred.
Hypothermia following intraventricular injection of hemicholinium‐3 in rats
Authors: SLATER P. 
Published: July 2012

In unanaesthetized rats, a dose of 50 μg of hemicholinium‐3 injected into the cerebral ventricles produced a prolonged hypothermia which was unaffected by the simultaneous administration of choline. This suggests that it was not due to inhibition of acetylcholine synthesis.
An intraperitoneal injection of 50 μg of hemicholinium‐3 also produced hypothermia which, however, was blocked by choline which suggests that it is due to inhibition of acetylcholine synthesis.
Hyoscine and hexamethonium did not block the hypothermia produced by intraventricular hemicholinium‐3, but some antagonism was obtained with phentolamine, imipramine and amphetamine.
When hemicholinium‐3 was administered intraventricularly to rats pretreated with desmethylimipramine, a lethal hyperthermia developed.
It is concluded that no central cholinergic mechanism is involved in the hypothermia of the rat resulting from an intraventricular injection of hemicholinium‐3.
The actions of some cholinomimetic drugs on the isolated taenia of the guinea‐pig caecum
Authors: HOBBIGER F. , MITCHELSON F. , RAND M. J. 
Published: July 2012

The actions on the taenia of 4‐(m‐chlorophenylcarbamoyloxy)‐2‐butynyltrimethylammonium chloride (McN‐A‐343), N‐benzyl‐3‐pyrrolidyl acetate methobromide (AHR‐602), tetramethylammonium (TMA) and choline phenyl ether have been examined and compared with the actions of acetylcholine, nicotine and 1,1‐dimethyl‐4‐phenylpiperazinium (DMPP).
Responses of the taenia to these agonists are quantitatively and often qualitatively dependent on the tone of the preparation. A method is described which makes allowance for the effect of tone on heights of contractions.
Acetylcholine, McN‐A‐343 and AHR‐602 produced only contractions; TMA produced contractions or biphasic responses; and choline phenyl ether, nicotine and DMPP produced contractions, relaxations or biphasic responses.
The mode of action of these compounds has been analysed by means of hyoscine, ganglion‐blocking drugs, tetrodotoxin and local anaesthetics.
It is concluded that acetylcholine, McN‐A‐343, AHR‐602, TMA and choline phenyl ether act on muscarinic receptors in the smooth muscle. Choline phenyl ether has an additional action on nicotinic receptors of cholinergic neurones. Nicotine and DMPP act on nicotinic receptors of cholinergic neurones and of inhibitory neurones. An action on the latter is sometimes also seen with TMA and choline phenyl ether.
With nicotine or DMPP, and TMA or choline phenyl ether in the presence of hyoscine, part of the contraction phase of biphasic responses (in which a contraction follows relaxation) is best explained as being triggered by the initial relaxation—that is, as a “rebound contraction”.
None of the compounds tested appeared to exert an atropine‐sensitive action on neurones.
In the presence of hyoscine high concentrations of agonists can act on sites not involved with lower concentrations.
The degree of antagonism obtained with procaine against compounds acting on muscarinic receptors on the smooth muscle varies with the compound tested.
Renal actions of dihydroergocristine and of phentolamine in anaesthetized cats
Authors: LOCKETT MARY F. , WADLEY ROSALIE 
Published: July 2012

. Comparison has been made of the effects of dihydroergocristine (DCS) and phentolamine mesylate (phentolamine) on cardiac and respiratory rates, systemic arterial pressure, renal clearances of creatinine (CCr) and of p‐aminohippuric acid (CPAH) and on the secretion of Na and K, in cats under chloralose anaesthesia.
. Phentolamine antagonized vasomotor tone and the pressor effect of circulating noradrenaline to comparable extent. The extent of reduction in urine flow, CCr, CPAH and Na excretion correlated with the fall in mean arterial pressure. Innervated and denervated kidneys responded similarly. Cardiac and respiratory rates rose slightly as arterial pressure fell.
. DCS, 10 to 20 μg/kg per min, did not reduce vasomotor tone, markedly reduced the pressor effect of exogenous noradrenaline, caused bradycardia and respiratory slowing but had little or no effect on renal function.
. DCS, 30 to 40 μg/kg per min, lowered mean arterial pressure by 15–25 mm Hg, decreased CPAH but not CCr, so raising the filtration fraction and caused a small reduction in urine flow and in Na excretion. Innervated and acutely denervated kidneys responded similarly.
. DCS, 30 to 40 μg/kg per min, raised mean arterial pressure, decreased CPAH, urine flow and Na excretion but did not alter CCr in animals pretreated with full α‐adrenergic blocking doses of phentolamine.
. DCS, 30 to 40 μg/kg per min, increased the rate of secretion of sympathetic amines from the adrenal medulla and increased the concentration of renin in renal venous blood.
. Isolated kidneys perfused at constant pressure from pump‐oxygenator circuits and in saline diuresis responded to DCS (15–17 μg/120 ml. blood) by diuresis and natriuresis and by a rise in the rate of secretion of renin. Higher concentrations of DCS (125–250 μg/120 ml.) were without effect on renal function and did not influence renin secretion.
. The renal effects of full α‐adrenergic blocking doses of DCS and of phentolamine were comparable, in the whole animal.
. The evidence indicates that the release of noradrenaline by DCS 30–40 μg/kg per min from nerve terminals supplying the juxtaglomerular apparatus may have caused the enhancement of renin secretion.
Effects of immobilization on rat liver tryptophan pyrrolase and brain 5‐hydroxytryptamine metabolism
Authors: CURZON G. , GREEN A. R. 
Published: July 2012

. Rat liver tryptophan pyrrolase increased on immobilization. The concentration of 5‐hydroxyindoleacetic acid in the brain also rose and that of 5‐hydroxytryptamine fell.
. When adrenalectomized rats were immobilized pyrrolase activity did not rise and brain 5‐hydroxytryptamine concentration fell to a lesser extent but the 5‐hydroxyindoleacetic acid concentration rose as in intact animals.
. When intact rats were injected with the pyrrolase inhibitor Allopurinol both the increase of pyrrolase and the fall of 5‐hydroxytryptamine on immobilization were less prominent but the concentration of 5‐hydroxyindoleacetic acid rose as before. Allopurinol did not affect the changes in immobilized adrenalectomized rats.
. Immobilization thus appears to cause (a) decreased brain 5‐hydroxytryptamine synthesis resulting from pyrrolase induction and (b) increased 5‐hydroxytryptamine breakdown by a more direct effect on the brain. Results of experiments on rats injected with lysergic acid diethylamide, and with α‐methyltryptophan or probenecid are consistent with the above interpretation.
. The 5‐hydroxytryptamine and 5‐hydroxyindoleacetic acid changes were maximal after 5–6 hours' immobilization and became less on more prolonged immobilization, which suggests regulatory changes.
The release of prostaglandin E1 from the rat phrenic nerve‐diaphragm preparation
Authors: LAITY J. L. H. 
Published: July 2012

. The release of prostaglandin E1 from the rat phrenic nerve‐diaphragm preparation during tetanic contraction of the muscle in response to nerve stimulation is reported. Tentative identification of the prostaglandin depended on solvent extraction column and thin‐layer chromatography and parallel biological assay.
. Polar lipid substances were released from the preparation in the absence of nerve stimulation by (+)‐tubocurarine and noradrenaline.
. The output on nerve stimulation was not abolished by (+)‐tubocurarine, hemicholinium, bretylium or phenoxybenzamine added to the bath.
. The possible origin of these prostaglandins is discussed.
Behavioural and somatic effects of bradykinin injected into the cerebral ventricles of unanaesthetized rabbits
Authors: GRAEFF F. G. , PELÁ IRENE R. , E SILVA M. ROCHA 
Published: July 2012

. The effects of bradykinin (1–5 μg) injected into the cannulated lateral cerebral ventricles were studied in unanaesthetized rabbits before and after intravenous atropine, diphemanil and morphine.
. The intraventricular injections of bradykinin produced a short‐lasting phase of behavioural excitation with vocalization followed by sedation. The behavioural excitation was associated with desynchronization in the electrocorticogram (e.co.g.), bradycardia and hypotension followed by tachycardia and hypertension. Tachypnoea was also observed. The subsequent phase of sedation was more prolonged and associated with synchronization of the e.co.g. and signs of catalepsy. Intense miosis was present during both phases.
. With repeated intraventricular injections of bradykinin, excitation, miosis, cardiovascular responses and tachypnoea diminished and eventually disappeared but the sedation did not exhibit tachyphylaxis.
. Atropine abolished the e.co.g. desynchronization, vocalization and bradycardia, reduced the duration of the excitatory and sedatory phase, diminished the tachycardia and hypotension, enhanced the hypertension, but did not affect the miosis and tachypnoea.
. Diphemanil affected only the cardiovascular effects produced by intraventricular bradykinin. They were affected in the same way as by atropine.
. Morphine did not affect the excitatory phase, but enhanced the cardiovascular effects produced by intraventricular bradykinin.
. The intraventricular injection of bradykinin (50 μg) caused a reduction in the amount of noradrenaline but not of 5‐hydroxytryptamine (5‐HT) in the brain stem; the amount of dopamine in the caudate nuclei was not affected.
. It is suggested that central cholinergic and adrenergic systems are activated by intraventricular bradykinin.
Effects of opiates and opiate antagonists on the Straub tail reaction in mice
Authors: ACETO M. D. , McKEAN DONNA B. , PEARL J. 
Published: July 2012

. Subcutaneous injections of opiates produced the Straub tail reaction in mice. The potencies of the opiates in mice were consistent with previous estimates of the analgesic potencies in animals and in man.
. The potencies of sixteen antagonists in counteracting the reaction were consistent with those previously obtained with the rat tail‐flick test.
. The (–) isomers of four benzomorphan derivatives were much more potent in counteracting the reaction than their (+) isomers and about twice as potent as their racemates. The activity of the isomers seemed to follow Pfeiffer's rule: the lower the effective dose of a drug, the greater the difference in the pharmacological effects of the optical isomers. One of the trans isomers acted like an opiate, while its cis isomer acted like an antagonist.
. Naloxone and nalorphine fulfilled conventional criteria for competitive antagonism, whereas atropine and the (–) and the (+) isomers of pentazocine and of cyclazocine did not do so.
. The Straub tail test seems to be useful for studying structure‐activity relations among opiates and opiate antagonists.
The mode of action of carbon tetrachloride on Fasciola hepatica
Authors: KHALIDI A. , ZAKI SANIHA AMIN 
Published: July 2012

. A biliary fistula was prepared in twelve sheep.
. Each animal was given 2 ml. of 14C‐carbon tetrachloride (specific activity 15 mc/m‐mole) and bile collected at 2, 4, 24 and 48 hr.
. Specific activity was measured by liquid scintillation counting before and after each specimen had been heated to 75°C for 10 min to drive off volatile content (carbon tetrachloride).
. Only traces of activity were present in the bile and heating did not alter this.
. There was no difference in the survival times of adult Fasciola hepatica incubated in Hedon Flieg medium with and without 25% bile from non‐medicated sheep, or with carbon tetrachloride in a concentration of 0.03%, but 25% of bile from sheep given 2 ml. of carbon tetrachloride 24 hr before greatly increased lethality in vitro.
. The anthelmintic action of carbon tetrachloride on F. hepatica does not result from a direct action due to excretion in bile of unchanged carbon tetrachloride but of an unidentified toxic element not necessarily derived from the drug but which arises as a result of its administration.
The action of general anaesthetic agents on root responses of the frog isolated spinal cord
Authors: RICHENS A. 
Published: July 2012

. The action of volatile and barbiturate general anaesthetic agents on synaptic transmission in the frog isolated spinal cord has been studied by recording ventral root synaptic potentials and spike discharges evoked by volleys in a dorsal root and in the lateral column fibres.
. Some observations on the distribution of the lateral column fibres and the characteristics of the dorsal root potentials have been presented.
. Volatile agents depressed and eventually abolished all components of the ventral root responses. Failure of motoneurone discharge was the result of two factors, a decrease in the slope of the synaptic potential and an elevation of the critical depolarization required to trigger propagated impulses.
. Barbiturate compounds, in contrast, readily abolished polysynaptic components of the ventral root responses, but the short latency discharge produced by lateral column stimulation was potentiated, and was accompanied by a lowering of the firing threshold of motoneurones. The mechanism of this potentiation by barbiturate compounds is discussed.
. It is concluded that volatile agents act predominantly on the initial segment and subsynaptic elements of the motoneurone, whereas barbiturate compounds depress the presynaptic or postsynaptic components of interneuronal synapses.