bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of thyroid hormones on the action of some centrally acting drugs
Authors: COVILLE P. F. , TELFORD J. M. 
Published: July 2012

Summary
. The effect of administration of thyroxine or thyroidectomy on the pharmacological action of (+)‐amphetamine, caffeine, hexobarbitone and morphine was determined in rats or mice.
. Locomotor activity induced by (+)‐amphetamine or caffeine was increased by hyperthyroidism and decreased by hypothyroidism.
. The LD50s of (+)‐amphetamine and caffeine in hyperthyroid rats were 1/30 and 2/5 that of control rats. With each drug, the LD50 regression lines in hyperthyroid and control rats were not parallel, suggesting that hyperthyroidism modifies the mechanism of the toxic effects. Hypothyroidism reduced toxicity to (+)‐amphetamine.
. Hexobarbitone sleeping time was prolonged in hyperthyroid male rats, but was shortened in hyperthyroid female rats. In control rats, sleeping time was approximately four times as long in females as it was in males. Ethinyloestradiol treatment and castration also prolonged sleeping time in male rats. No further prolongation was produced by combined administration of thyroxine and ethinyloestradiol, but thyroxine further prolonged the sleeping time of castrated rats indicating that its mode of action in producing these changes is not mediated via sex hormones.
. In contrast to rats, a sex difference in the duration of action of hexobarbitone was not found in mice. Thyroxine prolonged sleeping time equally in each sex.
. Analgesia induced by morphine in mice was unaffected by hyperthyroidism. No increase in sedative or ‘Straub tail’ activity could be detected, but toxicity was increased when higher doses of morphine were used.
. The mechanism by which thyroid hormones produce these changes in sensitivity to centrally acting drugs is discussed. It is suggested that the effects of thyroxine vary according to whether the mode of action of the drug or its metabolism is modified.
Investigations into the mechanism of the antifertility action of minimal doses of megestrol acetate in the rabbit
Authors: KENDLE K. E. , TELFORD J. M. 
Published: July 2012

Summary
. Experiments have been performed to investigate the mechanism by which low doses of megestrol acetate have an antifertility action.
. It was found that the dose of megestrol acetate required to prevent pregnancy in nine of ten New Zealand White rabbits when given on 3 consecutive days, the last of which was the day of insemination, was 50 μg/kg daily.
. This treatment reduced the numbers of sperm recoverable from the uterus at various times after insemination, but egg transfer experiments showed that neither egg viability nor fertilization was affected on day 1 of pregnancy.
. Treatment with megestrol acetate for 3 days caused the fertilized eggs to enter the uterus approximately 48 h prematurely. Treatment with megestrol acetate for longer periods caused a similar but more marked increase in the rate of transport of eggs in the oviduct.
. Megestrol acetate did not modify oviduct opening pressure, but the volume of oviduct fluid secretion was reduced earlier and transport of fluid through the oviduct was accelerated compared with controls.
. Transfer of eggs on various days from the uteri of untreated rabbits to the uteri of treated rabbits indicated that the development of the endometrium which occurs in pregnancy may be advanced by megestrol administration. Histological examination of the endometrial proliferation induced by megestrol acetate confirmed that this was so.
. It is concluded that the antifertility action of megestrol acetate in doses that do not necessarily inhibit ovulation is due to a combination of accelerated egg transport and advanced endometrial development.
Time course of the effects of 6‐hydroxydopamine on catecholamine‐containing neurones in rat hypothalamus and striatum
Authors: BELL LINDA J. , IVERSEN L. L. , URETSKY N. J. 
Published: July 2012

Summary
. The effects of intraventricular injection of 6‐hydroxydopamine (6‐OHDA) on tyrosine hydroxylase activity, uptake of 3H‐noradrenaline and endogenous catecholamine concentration in rat hypothalamus and striatum were investigated at various times after the injection of 6‐OHDA.
. In the hypothalamus after the injection of 250 μg of 6‐OHDA there was a rapid decrease in tyrosine hydroxylase activity, 3H‐noradrenaline uptake and noradrenaline content, which was essentially complete within 2 hours.
. In the striatum after this dose of 6‐OHDA there was a much slower reduction in tyrosine hydroxylase activity and 3H‐noradrenaline uptake during the first 48 h after drug injection. For the first 24 h the dopamine concentration in this brain area was increased significantly above control values, but had fallen below control values by 48 hours.
. After the injection of a smaller dose of 6‐OHDA (25 μg) the only detectable change in the striatum was a rapid increase in the dopamine concentration. In the hypothalamus this dose induced a rapid depletion of noradrenaline, not accompanied initially by any significant reduction in tyrosine hydroxylase activity.
. These results are consistent with the hypothesis that 6‐OHDA causes a rapid degeneration of catecholamine‐containing nerve terminals in the central nervous system (CNS). These degenerative changes, indicated by the loss of tyrosine hydroxylase and noradrenaline uptake sites, did not appear to be preceded by an initial displacement of endogenous catecholamines by 6‐OHDA, except possibly at early times after the administration of small doses of the drug.
Uptake of monoamines into central neurones and the blood‐brain barrier in the infant rat
Authors: LOIZOU L. A. 
Published: July 2012

Summary
. A fluorescence histochemical study was undertaken to investigate the ability of systemically administered monoamines to penetrate into the central nervous system of infant rats.
. It was found that after subcutaneous injections of large doses, l‐noradrenaline, l‐α‐methyl‐noradrenaline, dl‐α‐methyl‐dopamine, l‐α‐methyl‐dopa and 5‐hydroxytryptamine could cross the blood‐brain barrier of newborn to 2 week old rats and be taken up by neurones normally containing monoamine as well as by several neurones which normally contained no monoamine.
. 5‐Hydroxytryptamine containing neurones took up 5‐hydroxytryptamine as well as catecholamines and α‐methyl‐dopa. The pinealocytes, which contain large amounts of 5‐hydroxytryptamine, were depleted of their endogenous fluorescence by α‐methyl‐dopa and showed no selective uptake of catecholamines.
. The uptake of monoamines was not antagonized by previous reserpine treatment or by inhibition of catecholamine synthesis, and occurred throughout the whole extent of the monoamine‐containing neurones (cell body, axon, terminals).
. The monoamines were also taken up by the endothelial cells and pericytes of capillaries in the central nervous system (CNS) which are thought to constitute the physical barrier to these substances in the adult.
. The peripheral sympathetic nerves to pial blood vessels, the pineal and pituitary glands also took up the monoamines and α‐methyl‐dopa; uptake was also noted in cells of the pituitary gland, in epithelial and connective tissue elements of the meninges and choroid plexuses and in the epithelial, connective and muscular tissue of pial blood vessels.
. It is concluded that the blood‐brain barrier to monoamines may not be fully developed in infant rats, at least for high levels of circulating monoamines; the central monoamine‐containing neurones possess the ‘membrane pump’ mechanism for uptake of monoamines from the time of birth, even though they are not fully developed morphologically.
Effects of sulphydryl inhibitors on frog sartorius muscle: p‐chloromercuribenzoic acid and p‐chloromercuribenzenesulphonic acid
Authors: KIRSTEN E. B. , KUPERMAN A. S. 
Published: July 2012

Summary
. Experiments were done on frog sartorius muscles to study the effects and mechanisms of action of the –SH inhibitors, p‐chloromercuribenzoic acid (PCMB) and p‐chloromercuribenzenesulphonic acid (PCMBS).
. Both organomercurials produce a depolarization of the surface membrane which is associated with a period of asynchronous twitching and followed by inexcitability.
. Only PCMB produces a unique fractionation of the electrically evoked twitch into an initial rapid and later slow phase.
. PCMB and PCMBS increase the rate of 45Ca efflux from whole muscle. Ethylenediamine tetraacetic acid (EDTA, 5 mm) causes only limited antagonism of the enhancement of 45Ca efflux produced by PCMB whereas it completely antagonizes this same effect of PCMBS. EDTA selectively removes superficial calcium without penetrating into the intracellular space.
. The results suggest that PCMB inhibits –SH groups in the terminal cisternae causing a fractionation of the twitch. PCMBS acts primarily at surface sites with limited access to the cisternae and sarcoplasmic reticulum.
Effects of sulphydryl inhibitors on frog sartorius muscle: N‐ethylmaleimide
Authors: KIRSTEN E. B. , KUPERMAN† A. S. 
Published: July 2012

Summary
. The characteristic action of the –SH inhibitor, N‐ethylmaleimide (NEM), is muscle rigour. The dose‐response curve indicates a biphasic effect with maximum rigour tension produced by 10 mm NEM; beyond 1.0 mm there was an inverse relationship between dose and response.
. NEM produces a membrane depolarization unrelated to rigour development.
. NEM causes a sustained increase in 45Ca efflux from whole muscle. Pretreatment of a muscle with ethylenediamine tetra‐acetic acid (EDTA, 5 mm) to remove membrane calcium does not alter the NEM induced 45Ca efflux.
. It is suggested that the primary site of NEM action is inhibition of calcium uptake by the sarcoplasmic reticulum thereby producing rigour. At concentrations above 1.0 mm, NEM may affect the myofilaments.
Two toxins from a poisonous sample of mussels Mytilus edulis
Authors: EVANS M. H. 
Published: July 2012

Summary
. A crude preparation of toxin was extracted from a sample of mussels Mytilus edulis, part of a batch responsible for many cases of paralytic shellfish poisoning.
. The crude extract was partially purified by absorption on sodium Amberlite ion‐exchange resin. Two toxins were recovered by elution from the Amberlite, and purified further by gel filtration.
. One toxin closely resembled saxitoxin in its behaviour on Amberlite and in its biological effects.
. The other toxin behaved quite differently on the Amberlite. Its molecule was small, comparable in size with saxitoxin. It was not tetrodotoxin. Its biological effects were similar, but not identical, to those of saxitoxin: it paralysed muscular contraction and inhibited conduction along nerves; it caused death of experimental animals by producing a peripheral paralysis of respiration; it did not depolarize the membrane of frog skeletal muscle fibres, but acted by preventing a stimulus from initiating a conducted action potential.
. The biological effects of the second toxin suggest that, like saxitoxin and tetrodotoxin, it is an inhibitor of inward sodium ion movement through electrically excitable membranes.
Effects of stress and betamethasone on the production of corticosterone by the rat adrenal gland in vitro
Authors: HODGES J. R. , MITCHLEY SUSAN 
Published: July 2012

Summary
Production of corticosterone in vitro was studied using adrenal glands from rats which had been subjected to stress or treated with betamethasone.
An increase in corticosterone production occurred in the first but not the second hour of incubation in adrenals removed immediately after stress. When the interval between stress and adrenalectomy was longer, the increased corticosterone production persisted.
Betamethasone had no effect on corticosteroidogenesis in vitro when added directly to the incubation medium or when administered to rats shortly before removal of their adrenal glands.
Corticosteroidogenesis in vitro was considerably reduced in the adrenals of rats given prolonged treatment with betamethasone.
The significance of the results and the reliability of in vitro corticosteroid production as an index of hypothalamo‐pituitary‐adrenal activity is discussed.
Effect of tetrabenazine and α‐methyl‐m‐tyrosine on exploratory activity and brain catecholamines in rats
Authors: ONN‐LENG CHAN , WEBSTER R. A. 
Published: July 2012

Summary
Spontaneous exploratory locomotor activity of Wistar rats was measured in photocell activity cages, and brain noradrenaline (NA) and dopamine (DA) were determined fluorometrically after ion exchange purification.
Tetrabenazine (TBZ) (10 mg/kg) produced a fall in NA and DA concentrations in rat brain stems which was correlated with the fall in activity in female Wistar rats.
α‐Methyl‐m‐tyrosine (αMMT) reduced the concentration of rat brain NA without affecting DA concentration or activity.
Pretreatment with αMMT did not stop TBZ from producing a marked reduction in activity and NA concentration, but partially protected DA from the depleting action of TBZ.
These results support a role for catecholamines in the control of motor activity, but they do not implicate NA more than DA and they emphasize that the mechanism by which drugs affect the concentrations of catecholamines may be more important than the gross concentrations attained.
Cardiovascular effects of morphine, pethidine, diamorphine and nalorphine on the cat and rabbit
Authors: GRUNDY H. F. 
Published: July 2012

Summary
The predominant effect of morphine, diamorphine, pethidine or nalorphine on the blood pressure of the anaesthetized cat or rabbit is hypotension although, occasionally, a pressor action may predominate or intervene.
Possible mechanisms of the depressor phases of action have been studied on cardiac and vascular preparations both in situ and in vitro.
While in the whole animal, catecholamine release from the adrenal medulla and histamine liberation may be implicated in the responses, the vasodilator and vascular relaxant actions of morphine and, probably, pethidine, nalorphine and diamorphine on the isolated preparations are not mediated by the liberation of known peripheral transmitters or autacoids or by interaction with their specific receptors.
Inhibition by atropine of the increased turnover of noradrenaline in the hypothalamus of rats exposed to cold
Authors: SIMMONDS M. A. 
Published: July 2012

Summary
Small doses of (—)‐[3H] noradrenaline were injected into the lateral cerebral ventricles in rats to label radioactively the endogenous noradrenaline (NA) stores.
Intraventricular injection of 25 μg atropine methonitrate at the same time inhibited the increased rate of disappearance of [3H] NA from the hypothalamus at an environmental temperature of 9° C, when compared with the values at 24° C, without impairing temperature regulation.
At 32° C, 25 μg atropine methonitrate caused a lethal hyperthermia. A dose of 5 μg was not lethal and did not inhibit the increased rate of disappearance of [3H] NA from the hypothalamus.
It is concluded that the pathway which stimulates an increased turnover of NA in the cold contains an atropine sensitive synapse but is not the principal pathway of heat production. The increased turnover of NA in the heat probably does not involve an atropine sensitive synapse.
Effect of frequency of stimulation on the inhibition by noradrenaline of the acetylcholine output from parasympathetic nerve terminals
Authors: KNOLL J. , VIZI E. S. 
Published: July 2012

Summary
The relationship between the number of shocks delivered, the frequency of stimulation and the acetylcholine output per volley from nerve terminals of the longitudinal muscle strip of the guinea‐pig ileum was studied.
There was an inverse correlation between acetylcholine output per volley and the frequency of stimulation when the same number of shocks was applied in each train.
With sustained stimulation, the volley output declined more rapidly the higher the frequency of stimulation. There was no decrease in volley output (11·7 (ng/g)/volley) when the frequency applied was 0·1 Hz or less.
Noradrenaline (10−6 g/ml) reduced the acetylcholine output per volley to the level produced by sustained stimulation at 10 Hz (1·4–1·9 (ng/g)/volley). The acetylcholine output following application of the first shocks of a train at high frequency stimulation was much reduced by noradrenaline as the output was higher than 1·4–1·9 (ng/g)/volley. This action of noradrenaline was antagonized by phentolamine (2 μg/ml for 20 min).
Amphetamine and methylamphetamine, which release NA from sympathetic nerve terminals, were active in reducing the acetylcholine output to low frequency parasympathetic nerve stimulation. Reserpine and α‐methyl‐p‐tyrosine pretreatment prevented the effect of amphetamine and reduced that of methylamphetamine.
The fact that addition or release of noradrenaline, reduced acetylcholine output when the firing rate was high but short in duration, suggests that noradrenaline plays a general modulator role in controlling the output of acetylcholine from the parasympathetic nerve terminals.
Excitation of certain posterolateral hypothalamic units by cyclopropane and ether
Authors: MILLAR R. A. , SILVER I. A. 
Published: July 2012

Summary
Extracellular activity was recorded from single units in the posterolateral hypothalamus in nineteen cats before, during, and after the administration of the inhalation anaesthetics cyclopropane, diethyl ether and halothane.
Unit discharge was significantly increased by 25–50% cyclopropane in eighteen of the forty‐four cells tested with this anaesthetic, and in seven of fourteen cells tested with diethyl ether. This excitatory effect was associated with cortical EEG suppression.
The remaining cells tested were depressed by cyclopropane or ether, and this also occurred during halothane administration.
Excitation of certain cells in the posterolateral hypothalamus is discussed in relation to the increased preganglionic sympathetic activity evoked by cyclopropane and ether.
Factors affecting the action of guanethidine on adrenergic neurones
Authors: GULATI O. D. , JAYKAR SAROJA 
Published: July 2012

Summary
The uptake of guanethidine by adrenergic neurones has been studied indirectly by testing the ability of various procedures to prevent or reverse adrenergic neurone blockade in the periarterially stimulated isolated ileum preparation.
Adrenergic neurone blockade was prevented but not reversed by equilibration with guanethidine (3·3 × 10−6m) at low temperatures (10° C), in the absence of sodium or in the presence of tetrodotoxin (0·3 × 10−6m) or noradrenaline (1·2 × 10−3m).
Calcium (5 × 10−2m) both prevented and, to some extent, reversed the adrenergic neurone blocking action of guanethidine.
Equilibration with guanethidine in the presence of mersalyl (0·6 × 10−7m) or in the absence of potassium or calcium could neither prevent nor reverse adrenergic neurone blockade.
Release of dopamine from bovine lung by specific antigen and by compound 48/80
Authors: EYRE P. , DELINE T. R. 
Published: July 2012

Summary
Dopamine was shown to be released from the isolated lung of calves sensitized with horse serum by compound 48/80 and by specific antigen.
Dopamine contracts the bovine pulmonary artery and pulmonary vein. Phentolamine, the α‐adrenoceptor blocking agent, inhibits this activity of dopamine and also strongly reduces the Schultz‐Dale response of the pulmonary vessels.
The results are consistent with the suggestion that dopamine (together with histamine and 5‐hydroxytryptamine) may participate in the pulmonary vasoconstriction associated with anaphylaxis in cattle.
Effects of α‐methyl‐p‐tyrosine, p‐chlorophenylalanine, l‐β‐(3,4‐dihydroxyphenyl)alanine, 5‐hydroxytryptophan and diethyldithiocarbamate on the analgesic activity of morphine and methylamphetamine in the mouse
Authors: MAJOR C. T. , PLEUVRY BARBARA J. 
Published: July 2012

Summary
The analgesic activity of sympathomimetic drugs does not appear to involve a peripheral component.
Drugs causing changes in morphine analgesia have similar effects on the analgesia produced by methylamphetamine.
The analgesia produced by morphine and methylamphetamine is increased by drugs which increase the ratio of brain 5‐hydroxytryptamine (5‐HT) to dopamine.
The analgesia is decreased by drugs causing a fall in brain 5‐HT or a rise in dopamine relative to 5‐HT.
Action of 6‐hydroxydopamine on lamb sympathetic ganglia, vas deferens and adrenal medulla: a combined histochemical, ultrastructural and biochemical comparison with the effects of reserpine
Authors: CHEAH T. B. , GEFFEN L. B. , JARROTT B. , OSTBERG A. 
Published: July 2012

Summary
The effects of a single dose of 6‐hydroxydopamine (6‐OHDA) compared with those of chronic reserpine treatment were studied in lamb sympathetic neurones and adrenal medulla by a combination of fluorescence histochemistry, electron microscopy and radiochemical assay.
In sympathetic ganglia, 6‐OHDA produced a rise in noradrenaline concentration within 24 h, and falls in tyrosine hydroxylase and monoamine oxidase activities, whereas reserpine caused a fall in noradrenaline, a rise in tyrosine hydroxylase activity and no change in monoamine oxidase activity. The fluorescence of intra‐ and postganglionic axons increased greatly within 24 h of 6‐OHDA, and there was a corresponding accumulation of large dense‐core vesicles within many axons whose neurotubules were disrupted. The changes were almost reversed after 3 weeks.
In the vas deferens, the concentration of noradrenaline and tyrosine hydroxylase and monoamine oxidase activities had all fallen 24 h after 6‐OHDA treatment and had started to recover 3 weeks later. In the adrenal medulla, 6‐OHDA did not alter NA concentrations but increased tyrosine hydroxylase activity whereas reserpine depleted noradrenaline and increased tyrosine hydroxylase activity.
The changes produced in sympathetic ganglia by 6‐OHDA may be due both to a direct action on the axoplasmic transport of noradrenaline containing vesicles and indirectly to the reaction of the neurones to loss of the integrity of their axons.
Inhibitory effects of aprotinin on kallikrein and kininases in dog's blood
Authors: POJDA S. M. , VANE J. R. 
Published: July 2012

Summary
The blood‐bathed organ technique was used in dogs to estimate kinin generation in the blood. Strips of cat jejunum were used as assay tissues.
Infusions of kallikrein at 0·5–8 mu/ml into the blood in the extracorporeal circuit led to a generation of kinin at 0·6–10 ng/ml. The kinin generated was at the same concentration after incubation of kallikrein with blood for 15 s or 120 seconds. Intravenous infusions of kallikrein at (8–125 mu/kg)/min led to similar blood concentrations of kinin. These infusions induced substantial falls in blood pressure.
Aprotinin inhibited the generation of kinin by kallikrein, but the concentration needed in vivo was 20,000 times higher than would be expected from the definition of the units.
After intravenous injection of large doses of aprotinin, the kallikrein‐inhibiting activity passed off within 40–60 minutes. At the same time, there was a gradual reduction in kininase activity, so that the half life of bradykinin in blood increased from a mean of 13 s to 40 seconds. This effect reached a maximum 1–3 h after injection of aprotinin.
It is suggested that a metabolite of aprotinin is responsible for the kininase inhibition and that this effect may limit the usefulness of aprotinin in man.
Identification of prostaglandins in prevertebral venous blood after preganglionic stimulation of the cat superior cervical ganglion
Authors: DAVIS HEATHER A. , HORTON E. W. , JONES K. B. , QUILLIAM J. P. 
Published: July 2012

Summary
In four out of seven experiments, prostaglandin‐like activity was detected in prevertebral venous blood from the superior cervical ganglion, collected during and after preganglionic nerve stimulation.
Prostaglandins E1, E2, F2α and a prostaglandin A were identified using solvent partition, column and thin‐layer chromatography and bioassay techniques.
The release of PGF2α was confirmed by combined gas chromatography‐mass spectrometry.