bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of oestrogens and progestins on the response of mice to barbiturates
Authors: BLACKHAM A. , SPENCER P. S. J. 
Published: July 2012

. Mestranol (oestrogen) prolonged, whilst lynestrenol (progestin) reduced, the duration of pentobarbitone and hexobarbitone sleep in mice, whilst the effects of barbitone were not altered.
. The effects of these steroids on pentobarbitone sleep were dose‐related, did not show tachyphylaxis, and produced optimal effects after only 4 days pretreatment.
. The effects of lynestrenol were abolished by SKF 525A, whilst those of mestranol were markedly potentiated, suggesting a different mechanism and/or locus of action for mestranol and SKF 525A.
. Examination of plasma levels of pentobarbitone in mice pretreated with mestranol, lynestrenol or SKF 525A showed that lynestrenol increased whilst mestranol and SKF 525A reduced the rate of clearance of barbiturate from the plasma.
. The effects of lynestrenol disappeared when pentobarbitone was prevented from inducing hypothermia, whilst some significant prolongation of pentobarbitone sleep persisted in mestranol treated mice. This suggested that the ability to potentiate hypothermia was not the sole mechanism by which the effects of pentobarbitone were enhanced by mestranol.
. It is concluded these steroids alter the duration of action of pentobarbitone (and hexobarbitone) by changing the rate of barbiturate metabolism. In the case of mestranol, this might be a combination of an effect upon basal metabolic rate (enhancing hypothermia) and a direct effect on the liver. An effect upon renal clearance cannot be excluded by these results.
Further evidence for the involvement of kinin in anaphylactic shock in the rat
Authors: STARR M. S. , WEST G. B. 
Published: July 2012

. Sodium phenylbutazone, soya bean trypsin inhibitor, or the concomitant administration of ascorbic acid and mepyramine protected rats against anaphylactic shock at 10 days after sensitization but gave no protection against anaphylaxis at 20 days.
. During anaphylactic shock in rats at 10 days after sensitization, the plasma bradykinin and bradykininogen levels, as well as those in the intestinal lumen and peritoneal cavity, were markedly raised.
. The results support the hypothesis that there are two phases in anaphylaxis in the rat—an early phase in which bradykinin is a mediator and against which phenylbutazone or soya bean trypsin inhibitor or the mixture of ascorbic acid and mepyramine, give protection, and a late phase which does not involve bradykinin.
Hydrolysis of suxamethonium by different types of plasma
Authors: HOBBIGER F. , PECK A. W. 
Published: July 2012

. A method, based on the use of the isolated frog rectus abdominis preparation, is described for studying quantitatively the hydrolysis of suxamethonium at low concentrations.
. Rates of hydrolysis of butyrylcholine, 10 mM, benzoylcholine, 0.05 mM, and suxamethonium, 0.025 mM, by plasma from different species and human plasma with genetic variants of cholinesterase were measured.
. The rates of hydrolysis of suxamethonium by different types of plasma vary widely. Human plasma with usual cholinesterase and monkey plasma hydrolyse suxamethonium more speedily than do the plasma of cats, dogs and rats, and human plasma with either atypical or fluoride resistant cholinesterase. This is only to a small extent attributable to differences in enzyme concentration and not explained by the presence of an inhibitor.
. The Km values for butyrylcholine are very similar for different types of plasma but the KI values for suxamethonium in the system plasma‐butyryl‐choline‐suxamethonium vary greatly.
. These results and observations on the inhibition by decamethonium of the hydrolysis of butyrylcholine are consistent with the interpretation that the rates of hydrolysis of suxamethonium, 0.025 mM, obtained with different types of plasma vary because they are a function of two variables, the affinity of the ester for cholinesterase and the stability of the monosuccinyl derivative of the cholinesterase. It seems that human plasma with atypical cholinesterase hydrolyses suxamethonium much slower than does human plasma with usual cholinesterase mainly or solely because of differences in affinity of the ester for the two enzymes. On the other hand, cat plasma appears to hydrolyse suxamethonium much slower than does human plasma with usual cholinesterase mainly because the monosuccinyl derivative of cholinesterase in cat plasma is much more stable than that in human plasma. The reverse might apply for monkey plasma.
. Inhibition by dibucaine or sodium fluoride of the hydrolysis of benzoylcholine is not a general guide to rates of hydrolysis of suxamethonium by different types of plasma.
The effect of bretylium on intracellular cardiac action potentials in relation to its anti‐arrhythmic and local anaesthetic activity
Authors: PAPP J. GY. , WILLIAMS E. M. VAUGHAN 
Published: July 2012

. The initial effect of bretylium tosylate on isolated rabbit atria was to increase conduction velocity, contraction heights, spontaneous frequency and maximum driven frequency, and to reduce electrical threshold. At concentrations of 200 mg/l. or less, these were the only effects, and were consistent with the known sympathomimetic actions of bretylium.
. At extremely high concentrations, 1,200 and 2,400 mg/l., the initial actions were succeeded by weak quinidine‐like effects; reduced conduction velocity, spontaneous and maximum driven frequencies, and rate of rise of action potential. The electrical threshold was raised, but contraction heights were not reduced.
. The local anaesthetic activity of bretylium, measured by reductions in the frog nerve action potential, was 1/90 that of procaine and 1/300 that of propranolol, on a molar basis.
. Acute pretreatment with bretylium, 20 mg/kg intravenously, significantly increased the amount of infused ouabain required before the appearance of the first signs of atrial arrhythmia in anaesthetized guinea‐pigs, but did not prevent ventricular arrhythmias.
. Pretreatment with bretylium 30 mg/kg subcutaneously 24 hr, and again 4 hr before ouabain infusion, increased the dose of ouabain inducing atrial irregularity and slightly but significantly reduced the incidence of ventricular fibrillation.
The influence of psychotropic drugs on aldolase, mitochondrial malic dehydrogenase and Mg++Na+K+ adenosine triphosphatase
Authors: CHOWDHURY A. K. , ROGERS H. , SKINNER A. , SPECTOR R. G. , WATTS D. C. 
Published: July 2012

. The experiment investigated the effects of psychotropic drugs on enzymes in vitro.
. Chlorpromazine inhibits mitochondrial malate dehydrogenase in concentrations of 1·4 × 10−4m and above. No effect was observed below this concentration.
. A sharp inflection in the 1/V/drug plot was also seen with chlorpromazine (1·4 × 10−4m), trifluoperazine (1 × 10−5m), prochlorperazine (1 × 10−4m), and amylobarbitone (8 × 10−3m) acting on rat brain (Na+‐K+‐) Mg++‐ATPase and with chlorpromazine (10−4m) and imipramine (3 × 10−4m) acting on aldolase.
Quantitative studies on the antagonism by naloxone of some narcotic and narcotic‐antagonist analgesics
Authors: SMITS S. E. , TAKEMORI A. E. 
Published: July 2012

Naloxone was used to study the antagonism of the analgesic effects of some narcotics (morphine sulphate, levorphanol tartrate, and methadone hydrochloride) and narcotic antagonists (pentazocine, cyclazocine, and nalorphine hydrochloride). The analgesic assay used was the mouse phenylbenzoquinone stretching test.
The in vivo equivalent of a pA2 value (apparent pA2) for naloxone was determined with each agonist. These values were found to be significantly larger with the narcotics than with the narcotic antagonists.
The slopes in the apparent pA2 plots were also found to be significantly different. It was concluded that this difference in slopes was probably not due to a lack of equilibrium in one of the two groups of analgesics.
The results suggest that the narcotic and the narcotic‐antagonist analgesics may inhibit stretching in this assay by interacting either with two different receptors or with the same receptor in a different manner.
The effect of reserpine on the pressor responses to angiotensin in the conscious cat
Authors: DAY M. D. , OWEN D. A. A. 
Published: July 2012

Summary
Blood pressure recordings have been made in conscious cats in an attempt to reveal a possible indirect component to the angiotensin pressor response.
Reserpine (50 to 250 μg/kg per day) caused a maximal reduction of about 50% in the pressor response to angiotensin whilst virtually abolishing the responses to tyramine and McN‐A‐343. Responses to noradrenaline were only slightly and transiently reduced.
Syrosingopine (0.5 mg/kg) and reserpine (250 μg/kg) reduced the responses to angiotensin, McN‐A‐343 and tyramine to much the same extent, but tetrabenazine only reduced the responses to all these agents in a dose (25 mg/kg) which probably had effects on the catecholamine stores of smooth muscle.
The reduction in the responses to angiotensin, tyramine and McN‐A‐343 by reserpine was partly reversed by tranylcypromine. Noradrenaline and (±)‐dopa infusions were ineffective by themselves, but increased the effects of tranylcypromine in restoring the responses to angiotensin, tyramine and McN‐A‐343 after reserpine.
Infusion of α‐methyldopa markedly increased the responses to angiotensin, tyramine and McN‐A‐343 after these had been reduced by reserpine.
The results suggest that the pressor response to angiotensin in the conscious cat is partly mediated by release of noradrenaline from peripheral neuronal stores.
Antibacterial activity of dihydro‐1,3‐oxazine derivatives condensed with aromatic rings in positions 5, 6
Authors: CHYLIŃSKA J. B. , JANOWIEC M. , URBAŃSKI T. 
Published: July 2012

Summary
The antibacterial activity in vitro of dihydro‐1,3‐oxazine derivatives with aromatic rings condensed in positions 5, 6 was examined.
Of more than thirty compounds examined, two (T 615 and T 638) showed marked activity against various strains of Mycobacterium tuberculosis at concentrations below 2 μg/ml.
These two compounds also showed marked activity against Escherichia coli, Clostridium pneumoniae and Salmonella typhi.
Both showed marked activity in vivo against tuberculosis produced in mice and guinea‐pigs by various strains of Mycobacterium such as human strain ‘Sz’, bovine ‘An 5’ and H37Rv non‐resistant and resistant to isonicotinic acid hydrazide (INH), streptomycin (SM) and p‐aminosalicylic acid (PAS).
Inhibitory and excitatory effects of sympathomimetic amines on muscle strips from the stomach of the guinea‐pig
Authors: BAILEY DIANA M. 
Published: July 2012

Summary
Responses of muscle strips from the stomach of the guinea‐pig have been recorded. Sympathomimetic amines cause inhibitory, motor or biphasic responses.
The motor components of the responses of the preparations were greatly enhanced by the removal of the mucosal layers.
The inhibitory responses to isoprenaline, noradrenaline and phenylephrine were antagonized by propranolol or by sotalol. The inhibitory responses to noradrenaline and phenylephrine but not isoprenaline were antagonized by phentolamine. Therefore, both α‐ and β‐adrenoceptors may subserve inhibition.
The motor responses to noradrenaline and phenylephrine were often potentiated by propranolol or sotalol and were antagonized by phentolamine. Therefore, motor responses to sympathomimetic amines appear to involve α‐adrenoceptors.
The responses to sympathomimetic amines and their antagonists were not modified by hyoscine or by tetrodotoxin. It is concluded that the adrenoceptors mediating the responses recorded from these preparations are located on the smooth muscle cells rather than on a nervous pathway.
Response to acetylcholine and nicotine of the perfused vessels of the rabbit ear
Authors: GRAHAM J. D. P. , SUHAILA A. , TAI A. 
Published: July 2012

Summary
The vessels of the isolated rabbit ear were perfused at 23 mbar with Krebs solution with (tonic) and without (atonic) noradrenaline (5.9 × 10−7M) at selected temperatures of 20°–38° C. Peripheral resistance units (PRU) were calculated from the observed peak flow rates and alterations caused by drugs expressed as Δ% PRU.
ACh is constrictor in the atonic vessel.
ACh is a vasodilator of the tonic vessel perfused with NA. This effect is potentiated by anticholinesterase and by denervation, unaffected by botulinum toxin and antagonized by atropine. ACh also dilates the vessel perfused with vasopressin.
Increasing the temperature reduces the responses to ACh but increases the effect of anticholinesterase.
Nicotine causes a dose dependent dilatation of the tonic vessels, reduced but not abolished by C6, by atropine, by botulinum toxin and by denervation.
Nicotine causes a dose dependent constriction of the atonic vessels, abolished by C6 and by phentolamine, reduced by denervation, but unaffected by botulinum toxin.
Metabolism of small multiple doses of (14C) nicotine in the cat
Authors: TURNER D. M. 
Published: July 2012

Summary
The distribution and metabolism of (2′‐14C) nicotine given as a series of small intravenous injections (4 μg/kg every 60 s for 20 min) have been studied in the cat.
Blood concentrations of (14C) nicotine reached a maximum of 100 ng/ml at 20 min whereas blood concentrations of cotinine were maximal shortly afterwards.
The maximum concentration of nicotine in the blood was greater than that obtained by giving the same total dose as a continuous infusion ((4 μg/kg)/min for 20 min).
Urinary excretion accounted for 90% of the total multiple dose in 72 hours. After 24 h, however, only 2.5% of the radioactivity as (14C) nicotine and 0.05% as (14C) cotinine was excreted.
Gastric juice after 2 h contained significant amounts of activity which was almost entirely composed of (14C) nicotine and (14C) cotinine.
There were significant regional differences in the concentration of (14C) nicotine in the brain; amounts were greatest in cerebral hemispheres and smallest in the spinal cord. The hypothalamus and thalamus contained significantly higher concentrations of (14C) nicotine than the whole mid brain. (14C) Cotinine concentrations were highest in the cerebellum.
An implanted reservoir of morphine solution for rapid induction of physical dependence in rats
Authors: GOODE P. G. 
Published: July 2012

Summary
Rats were dosed continuously with morphine hydrochloride by giving a daily dose through tubes connected to small, subcutaneously implanted reservoirs. Morphine was withdrawn by washing out the reservoir with drug vehicle. The daily dose of morphine, or substitute drug received by each rat was determined by difference by estimating the drug remaining in reservoir washings.
Withdrawal symptoms were more pronounced after 9 days than after 4 days of dosing with morphine.
Body weight loss, maximal at 24 h, and increased defaecation during the first 7 h were the chief physiological signs of morphine withdrawal. The body weight loss was the result of hypodipsia and anorexia exacerbated by increased defaecation.
When substituted for morphine in the reservoir, methadone and codeine completely prevented body weight loss and increased defaecation. while pethidine was effective against increased defaecation, but not against 24 h body weight loss. The opiate‐antagonist analgesics pentazocine, nalorphine and cyclazocine either had no effect on withdrawal symptoms or increased their severity.
In morphine dependent rats under continued morphine administration subcutaneous doses of the opiate‐antagonists nalorphine, cyclazocine and naloxone all precipitated the withdrawal symptoms of body weight loss and increased defaecation. The weak antagonist pentazocine caused a significantly increased defaecation, but no significant change in body weight, while the opiates pethidine. codeine and methadone had no significant effect on body weight or defaecation.
The advantages of inducing dependence by this method of dosing are discussed.
Resistance of noradrenaline in blood vessels to depletion by 6‐hydroxydopamine or immunosympathectomy
Authors: BERKOWITZ B. A. , SPECTOR S. , TARVER J. H. 
Published: July 2012

Summary
The degree of the decrease in the noradrenaline concentrations caused by 6‐hydroxydopamine or immunosympathectomy was different in different areas of the cardiovascular system.
In rats or guinea‐pigs 6‐hydroxydopamine depleted the noradrenaline content of the heart by 90%, of the mesenteric vein by 80% and of the mesenteric artery and aorta by 30–60%. Immunosympathectomy elicited a 70% reduction in the cardiac noradrenaline but only a 50% reduction in the noradrenaline of the blood vessels of the rat.
The tyrosine hydroxylase activity of the heart, blood vessels, or adrenal glands was not significantly altered 2 weeks after 6‐hydroxydopamine. Nor was the monoamine oxidase activity in heart or blood vessels changed.
The inconsistent ability of both 6‐hydroxydopamine and immunosympathectomy to abolish experimental hypertension may be due to the partial persistence of noradrenaline and functional sympathetic nervous system activity in the blood vessels.
Effects of formyl tetrahydrofolic acid and noradrenaline on the oxygen consumption of rat brain synaptosome‐mitochondrial preparations
Authors: SPECTOR R. G. 
Published: July 2012

Summary
The respiration of a mitochondrial and synaptasome fraction of rat cerebral cortex was measured using an oxygen electrode.
Little or no enhancement of oxygen uptake occurred on separately adding formyl tetrahydrofolate or noradrenaline.
When these substances were added together a marked increase in respiration was observed.
Both phenobarbitone and phenytoin inhibited the respiration of this preparation, but this was reversed on the addition of formyl tetrahydrofolate.
The possibility that some antiepileptic drugs may compete with formyl tetrahydrofolate in the brain is considered and structural similarities between folic acid and these drugs are indicated.
Studies on the effect of physostigmine on experimental cardiac arrhythmias in dogs
Authors: DAS P. K. , BHATTACHARYA S. K. 
Published: July 2012

Summary
Experimental cardiac arrhythmias were produced in dogs anaesthetized with pentobarbitone. Ventricular arrhythmias were induced by strophanthin‐K, light petroleum plus adrenaline or coronary ligation procedures. Atrial flutter was induced by an injury‐stimulation technique. The acetylcholine and glycogen concentrations of the atria and ventricles were estimated.
Physostigmine pretreatment (0·1 mg/kg) significantly reduced the incidence of ventricular arrhythmias after myocardial ischaemia but had no effect on any of the other arrhythmias.
Physostigmine markedly increased the acetylcholine concentrations of atria and ventricles in control dogs, to nearly the same extent. Physostigmine had no effect on ventricular acetylcholine concentrations in dogs treated with strophanthin‐K and light petroleum plus adrenaline but in the coronary ligation group it caused a significant increase in the acetylcholine concentrations of both atria and ventricles, and of atrial acetylcholine only in the injury‐stimulation group.
All the arrhythmias produced marked glycogenolysis of both the atria and the ventricles, to nearly the same extent. Although physostigmine produced marked glycogenolysis in the control dogs it significantly inhibited cardiac glycogenolysis after light petroleum plus adrenaline, atrial glycogenolysis after strophanthin‐K‐induced arrhythmias and ventricular glycogenolysis after myocardial ischaemia.
There appears to be a possible correlation between the increase in the acetylcholine concentration of the ventricles and anti‐arrhythmic actions of physostigmine, but there is a less clear correlation between changes in the glycogen concentration of ventricles and the anti‐arrhythmic action.
Pharmacological studies on the hypogastric ganglion of the rat and guinea‐pig
Authors: BENTLEY G. A. 
Published: July 2012

Summary
Preparations were developed whereby the hypogastric ganglion of the rat or guinea‐pig was perfused through its vasculature with saline solutions. Drugs were injected into the perfusion stream, and their effects were indicated by contractions of the vas deferens. The base of this organ could be ligated to prevent the drugs reaching the smooth muscle via the blood vessels. For comparison, experiments were also performed on fully isolated preparations of the rat and guinea‐pig hypogastric nerve‐vas deferens, where the vas deferens was held in an inner bath, so that drugs added to the outer bath could act only on the ganglion. Attempts were made to demonstrate non‐nicotinic receptors in these preparations.
It was shown that the perfused hypogastric ganglion of the guinea‐pig would respond repeatedly to several nicotinic stimulants, though autodesensitization eventually occurred. The fully isolated preparation behaved similarly, but desensitized much more rapidly. In contrast, the rat ganglion, either perfused or fully isolated, was remarkably insensitive to nicotinic stimulant drugs.
Neither species responded well to non‐nicotinic stimulants; that from the guinea‐pig gave small contractions to methacholine in about 33% of cases, but did not respond to (4‐m‐chlorophenyl‐carbamoyloxy)‐2‐butynyl trimethylammonium chloride (McN‐A‐343). With the rat, the situation was opposite.
The guinea‐pig ganglion did not become more sensitive to non‐nicotinic stimulants after some treatments known to sensitize the cat superior cervical ganglion. These include preganglionic tetanization, chronic decentralization, and removal of all potassium. Sensitization did occur, however, in the presence of physostigmine, after tachyphylaxis to dimethyl phenyl piperazinium iodide (DMPP) had developed, and when the preparation was perfused with a suspension of washed erythrocytes.
It is concluded that the responses of sympathetic ganglia vary from one species to another, and according to whether the organs are perfused or fully isolated.
Morphine hyperthermia in the rat: its attenuation by physostigmine
Authors: SHARKAWI M. 
Published: July 2012

Summary
In rats, a subcutaneous injection of morphine (2·5 mg/kg) produced hyperthermia which was greatly attenuated by an intraperitoneal injection of physostigmine (0·1 mg/kg), but not of neostigmine (0·08 mg/kg) and promptly reversed by a subcutaneous injection of nalorphine.
It is concluded that the hyperthermia is a specific response to morphine, central in origin, and the result of diminished acetylcholine (ACh) release from central cholinergic neurones.
Isolation and identification of pharmacologically active amino acids in skin and their structure‐activity relationship on the guinea‐pig ileum
Authors: LEWIS G. P. , McMARTIN C. , ROSENTHAL S. R. , YATES CATHERINE 
Published: July 2012

Summary
. Aqueous extracts of stratum corneum were found to cause histamine‐like contractions of the guinea‐pig ileum which were not antagonized by mepyramine, atropine or bromolysergic acid diethylamide.
. The compounds responsible for this contraction were isolated by chromatography and shown to be common amino acids, particularly l‐serine and l‐alanine which occur in abundance in the stratum corneum.
. Amino acid analogues were assayed on the guinea‐pig ileum against alanine as standard. With the exception of γ‐amino butyric acid and l‐alanine benzyl ester all analogues which had appreciable activity gave dose‐response curves parallel to l‐alanine.
. The response to l‐alanine benzyl ester was abolished by mepyramine and this analogue appears to be a partial agonist on the histamine receptor.
. The effects of substitution on the equipotent molar ratios of amino acid analogues indicate that all four chemical groups attached to the α‐carbon of l‐alanine interact with the receptor.
. Our results suggest that the guinea‐pig ileum contains an l‐α‐amino acid receptor.