bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of phenobarbitone, leptazol, dexamphetamine, iproniazid, imipramine, LSD, chlorpromazine, reserpine and hydroxyzine on the in vivo levels of adenine nucleotides and phosphocreatine in the rat brain
Authors: WILSON W. S. 
Published: July 2012

Enzymic and ion‐exchange chromatographic analyses were used to measure adenosine triphosphate (ATP), diphosphate (ADP) and monophosphate (AMP) in brain extracts from rats treated with a wide range of centrally acting drugs. Phosphocreatine (PC) was assayed by the acid molybdate method.
An anaesthetic dose of phenobarbitone caused an increase in brain levels of ATP and PC, and a reduction in ADP and AMP. A convulsant dose of leptazol gave rise to precisely opposite effects. Subanaesthetic (hypnotic) and subconvulsive doses of the two drugs, respectively, produced no alterations in brain nucleotide levels.
Among the psychotropic drugs, dexamphetamine, LSD and hydroxyzine, at the doses used, caused no changes in brain levels of the adenine nucleotides. Iproniazid and imipramine caused slight increases in the ATP level and ATP/ADP ratio, respectively. Chlorpromazine failed to give rise to any effect in the nucleotides 3 hr after administration, but produced a rise in brain ATP after 6 hr. Reserpine, on the other hand, caused a fall in the ATP/ADP ratio 6 hr after injection.
These results indicate that some psychotropic drugs can cause small changes in the rat brain ATP/ADP ratio but do not support claims by certain workers that such changes correlate closely with the behavioural effects of these drugs.
The interaction between monoamine oxidase inhibitors and narcotic analgesics in mice
Authors: ROGERS K. J. , THORNTON J. A. 
Published: July 2012

The administration of either iproniazid or tranylcypromine to mice potentiates the acute toxicity of pethidine, morphine, pentazocine and phenazocine.
Blood levels of pentazocine in mice pretreated with tranylcypromine do not differ from the levels in animals not receiving the monoamine oxidase (MAO) inhibitor.
There is no correlation between changes in brain and liver MAO activity and the increased pethidine toxicity.
A comparison is made between the change in pethidine toxicity and the changes in the concentration of cerebral noradrenaline, dopamine and 5‐hydroxytryptamine following the injection of tranylcypromine.
It is concluded that the increased toxicity of potent analgesics in combination with MAO inhibitors is not due to a decelerated metabolism of the analgesic drug, but is related to an increased concentration of cerebral 5‐hydroxytryptamine. A critical level of this monoamine, in the brain, may be necessary before the drug interaction will take place.
Ionic interactions in acetylcholine contraction of the denervated rat diaphragm
Authors: FREEMAN SHIRLEY E. , TURNER R. J. 
Published: July 2012

The nature of the drug‐receptor interaction in the acetylcholine‐induced contraction of the denervated rat diaphragm was studied both by altering the external ionic environment and by determining its drug sensitivity.
The response to acetylcholine was insensitive to tetrodotoxin or saxitoxin, but was abolished by procaine.
It was unaffected by levels of MnCl2 sufficient to block the response of the innervated diaphragm to electrical stimulation, although higher levels reduced the response. The effect of Mn++ on the innervated diaphragm was overcome by raising the external Ca++ level; this was ineffective in the denervated preparation.
In spite of its insensitivity to tetrodotoxin the acetylcholine contraction was reduced and prolonged by low external Na+ levels. This prolongation was not found when Li+ substituted for Na+.
Increasing the external level of Ca++ or Mg++ 3 to 5‐fold reduced the acetylcholine contraction; high Ca++ also prolonged it. Reduction in the divalent cation level was without effect.
Procaine inhibition of the acetylcholine response was largely competitive, as was inhibition due to (+)‐tubocurarine. This was shown by probit analysis and the dose‐ratio test.
Thiocyanate (12 mm) augmented and prolonged the contraction; this action was modified by altering the Ca++ or Mg++ level of the solution.
The acetylcholine receptor resembles that of the innervated postsynaptic membrane.
Reversal by pronethalol of dibenamine blockade: a study on the seminal vesicle of the guinea‐pig
Authors: GUIMARÃES S. 
Published: July 2012

The guinea‐pig seminal vesicle has been shown to be a very suitable test object for the study of mechanisms involving α‐adrenoceptive receptors, because no β‐receptors were found in this preparation.
Adrenaline, noradrenaline and phenylephrine were directly acting agonists, their ED50 values being 7·1 × 10−6M, 1·5 × 10−5M and 2·7 × 10−5M, respectively.
Pretreatment with reserpine had no influence on the contractions caused by adrenaline, noradrenaline and phenylephrine but abolished or greatly reduced the contractions caused by dopamine. Cocaine enhanced the effects of adrenaline, noradrenaline and phenylephrine and reduced those of dopamine.
Pronethalol (6·8 × 10−5M) reversed the α‐receptor blockade by dibenamine, ergotamine and phentolamine of responses to adrenaline, noradrenaline and phenylephrine; it did not affect the blockade by dibenamine of responses to histamine.
Reversal of the blockade by dibenamine was observed only when its concentration was such that it caused a parallel shift of the dose‐effect curves of the agonists to the right; higher concentrations, which caused an unsurmountable depression of the maximal contraction, were not antagonized by pronethalol.
It is assumed that the reversal is dependent on a direct action on α‐receptors, “spare receptors” being probably involved.
PMN‐kinin and kinin metabolizing enzymes in normal and malignant leucocytes
Authors: GREENBAUM L. M. , FREER R. , CHANG J. , SEMENTE G. , YAMAFUJI K. 
Published: July 2012

Studies have been carried out on the kinin‐forming and kinin destroying activity of rabbit macrophages obtained from the lung before and after BCG injection and from the peritoneal cavity following mineral oil injection. A similar study was carried out with L‐1210 leukaemic cells obtained from the peritoneal cavity of mice.
The macrophages and leukaemic cells contain enzymes that form kinins from purified kininogen substrates at acid pH. The kinin‐forming activity is not limited to the lysosomal fraction of the cell since it is found in extra‐lysosomal compartments. Delta‐guanidovaleryl benzyl ester partially inhibits the kinin‐forming activity. Trasylol does not inhibit the kinin‐forming activity of these cells, but does inhibit the kininases of these cells. The lack of effectiveness of this agent as a general anti‐inflammatory agent is thus explained.
The kininases of the normal and malignant cells are also inhibited by chloromethyl ketones such as tosyl‐lysine chloromethyl ketone (TLCK) and tosyl‐phenylalanine‐chloromethyl ketone (TPCK) as well as by copper salts. Hydroxyquinoline has no inhibitory action on these cells, indicating that they differ from the plasma kininases.
Investigation of the kinins produced by enzymes in rabbit and human polymorphonuclear (PMN) cells has demonstrated the formation of a kinin that differs from bradykinin and other known mammalian kinins in its pharmacological properties, molecular weight, and amino‐terminal end group. This peptide has been named PMN‐kinin.
Overall, the investigation has demonstrated the importance of white cells in contributing to the formation and destruction of “extra‐plasma” sources of kinins by enzymes which differ from plasma enzymes. Anti‐inflammatory agents may have different actions on these cell enzymes from those on plasma enzymes.
Excitatory action of sympathomimetic amines on 5‐hydroxytryptamine receptors of gut
Authors: INNES I. R. , KOHLI J. D. 
Published: July 2012

Twenty‐two sympathomimetic amines were tested for excitatory activity on isolated guinea‐pig ileum, rabbit jejunum, and rat stomach.
Eight amines contracted all or almost all guinea‐pig ileum preparations; five amines contracted half the preparations and relaxed the others. Nine amines were consistently relaxant. Structural requirements for excitatory activity were not clear.
Six amines contracted rat stomach and only four contracted rabbit jejunum. Only β‐phenylethylamine and (—)‐amphetamine contracted all three preparations.
The excitatory effects of the sympathomimetic amines on guinea‐pig ileum seem to be due to an action on 5‐hydroxytryptamine receptors. This conclusion is based on evidence that their excitatory action is antagonized by 2‐bromo‐Iysergic acid diethylamide, by morphine and by desensitization with 5‐hydroxytryptamine, and that there is cross‐protection between 5‐hydroxytryptamine and the excitatory sympathomimetic amines against block by phenoxybenzamine.
The pharmacology of fenclozic acid (2‐(4‐chlorophenyl)‐thiazol‐4‐ylacetic acid; I.C.I. 54, 450; ‘Myalex’); a new compound with anti‐inflammatory, analgesic and antipyretic activity
Authors: NEWBOULD B. B. 
Published: July 2012

Fenclozic acid (2‐(4‐chlorophenyl)thiazol‐4‐ylacetic acid; I.C.I. 54, 450; “Myalex”) is one representative of a new class of compounds with antiinflammatory, analgesic and antipyretic properties as evidenced by its activity in a variety of tests in rats, mice and guinea‐pigs.
In tests of short duration the potency of fenclozic acid is similar to that of phenylbutazone.
In tests of longer duration fenclozic acid is more potent than phenylbutazone.
The activity of fenclozic acid is not mediated by stimulation of the adrenals and the compound is devoid of corticosteroid‐like activity.
Mechanism of the antagonism between guanethidine and dexamphetamine
Authors: GERKENS J. F. , McCULLOCH M. W. , WILSON J. 
Published: July 2012

The effects of dexamphetamine were studied on the responses of rabbit ileum, rabbit ear artery and sheep spleen to sympathetic nerve stimulation after exposure to guanethidine and in the absence of guanethidine.
In the absence of guanethidine, dexamphetamine enhanced the responses to sympathetic stimulation and, in the spleen, this was shown to be due to an increase in noradrenaline output. However, the increase in these responses was much less than the increase obtained in preparations treated with guanethidine.
Cocaine, in a concentration which produced the same effect on noradrenaline uptake as the concentration of dexamphetamine used, was also effective in reversing the adrenergic neurone blocking actions of guanethidine.
It is suggested that the antagonism between dexamphetamine and guanethidine is due to a reduction in the uptake of guanethidine by the nerve endings rather than to interaction of the two drugs at the receptor site for the adrenergic neurone blocking action of guanethidine.
Role of adrenal hormones in the synthesis of noradrenaline in cardiac sympathetic neurones
Authors: BHAGAT B. 
Published: July 2012

. Adrenalectomy or adrenal demedullation affected neither the levels of endogenous catecholamines in the rat heart nor the accumulation of 3H‐noradrenaline 1 hr after its intravenous administration.
. Twenty‐four hours after intravenous administration of labelled amine, however, its retention was markedly reduced in the heart of adrenalectomized or demedullated rats. Ganglionic blockade prevented this reduction.
. Rate calculations from the decline of catecholamine levels after blockade of synthesis with α‐methyl‐tyrosine showed that cardiac synthesis of noradrenaline increased about four‐fold after demedullation and about three‐fold after adrenalectomy. This increase in synthesis may compensate for the loss of circulating catecholamines.
. There was no change in catechol‐o‐methyl‐transferase activity, but monoamine oxidase activity was increased in the homogenates of the heart of adrenalectomized and demedullated rats. The increase in the cardiac monoamine oxidase activity was markedly greater in the adrenalectomized rats than in the demedullated rats.
. It is suggested that adrenal cortex insufficiency may modulate the rate of synthesis of noradrenaline and monoamine oxidase activity in cardiac sympathetic neurones.
The metabolism of orally administered l‐DOPA in Parkinsonism
Authors: CALNE D. B. , KAROUM F. , RUTHVEN C. R. J. , SANDLER M. 
Published: July 2012

. Gas‐liquid chromatographic methods were used to measure urinary acidic and alcoholic metabolites of l‐DOPA, which had been administered in high oral dosage to patients with postencephalitic and idiopathic Parkinsonism.
. The output of these compounds was normal before treatment. During drug therapy, large quantities of the dopamine metabolites, homovanillic acid and dihydroxyphenylacetic acid, were excreted but traces only of 4‐hydroxy‐3‐methoxyphenylethanol. Noradrenaline metabolites showed little change in output other than a small increase in 4‐hydroxy‐3‐methoxymandelic acid.
. Information was obtained about a number of minor routes of degradation which might be implicated in the therapeutic action of l‐DOPA. A raised output of m‐hydroxyphenylacetic acid pointed to p‐dehydroxylation of dihydroxyphenylacetic acid by gut flora. Evidence of transamination as a minor metabolic pathway was obtained by finding appreciable urinary levels of 4‐hydroxy‐3‐methoxyphenyllactic acid. A keto‐acid precursor of this compound may act as competitive inhibitor of an enzyme active in the normal degradation route of tyrosine, p‐hydroxyphenylpyruvic acid oxidase, for increased amounts of p‐hydroxyphenyllactic acid, the major metabolic derivative of p‐hydroxyphenylpyruvic acid, accumulated in the urine during DOPA treatment.
Effect of monoamineoxidase inhibitors on 5‐hydroxytryptamine output from perfused cerebral ventricles of anaesthetized cats
Authors: GOODRICH CECILIE A. 
Published: July 2012

. In cats anaesthetized with pentobarbitone sodium, intraperitoneal injections of four inhibitors of monoamine oxidase (MAO) were shown to increase the 5‐hydroxytryptamine (5‐HT) in the effluent from the perfused cerebral ventricles.
. Weight for weight, tranylcypromine was found to be about twice as potent as pheniprazine, eight times as potent as nialamide and sixty times as potent as pargyline.
. The effect of tranylcypromine was also examined after reserpine had been injected into the cerebral ventricles or after p‐chlorophenylalanine, given intraperitoneally. In both conditions tranylcypromine retained its ability to increase the 5‐HT output from the perfused cerebral ventricle, but the effect was attenuated, more after p‐chlorophenylalanine than after reserpine.
. Evidence is put forward that in both conditions the brain is not completely depleted of its 5‐HT, but that the 5‐HT is only reduced, more after p‐chlorophenylalanine than after reserpine.
A sequential screening test based on the running component of audiogenic seizures in mice, including reference compound PD50 values
Authors: COLLINS A. J. , HORLINGTON M. 
Published: July 2012

. The running component of audiogenic seizures in mice has been used as the basis of a sequential screening test for the detection of a variety of centrally acting drugs.
. For acceptance by the test, an active compound must completely suppress the running component in a total of sixteen mice at a dose of 1/5 LD50 intraperitoneally.
. Considerable economies in the numbers of animals required for screening have been achieved, the mean number of mice required to reject an inactive compound being 2ṁ0.
. The running component is highly sensitive to anticonvulsants and general central depressants, and insensitive to phenothiazine tranquillizers and morphine. Reserpine caused an increase in the severity of the running component.
. The statistical model used in this test is of general application to screening test situations which use quantal data.
The pharmacology of the cholinoceptor in muscle preparations of Ascaris lumbricoides var. suum
Authors: NATOFF I. L. 
Published: July 2012

. The preparation of a muscle strip of Ascaris lumbricoides for the study of the effect of drugs in vitro is described.
. Stimulant drugs which are classified as nicotine‐like in mammalian pharmacology increased the isometric tension of this preparation. These drugs were, in descending order of potency: dimethylphenylpiperazinium, nicotine, acetylcholine, carbachol, decamethonium and pyridine‐2‐aldoxime methiodide.
. Muscarine‐like drugs (oxotremorine, methacholine, pilocarpine) had no activity.
. Potassium and barium ions stimulated the tissue, while the anti‐cholin‐esterases, dichlorvos and eserine, increased the resting tension of the preparation and potentiated the responses to acetylcholine.
. Adrenaline neither stimulated the tissue nor affected the responses to nicotine‐like drugs.
. The relative potency of several blocking agents which antagonize the responses to nicotine‐like drugs was assayed. These blocking agents were, in descending order of potency: mecamylamine, (+)‐tubocurarine, hexamethonium, atropine and piperazine. Acetylcholine, dimethylphenylpiperazinium and pyridine‐2‐aldoxime methiodide apparently act on a common receptor, for each blocking agent had a similar molar inhibitory concentration against these stimulants.
. It is concluded that the cholinoceptor in muscle preparations of Ascaris lumbricoides is pharmacologically similar to that of the mammalian autonomic ganglion.
The effect of a large dose of atropine upon the performance of routine tasks
Authors: MOYLAN‐JONES R. J. 
Published: July 2012

. A field trial was conducted in order to assess the effect upon tasks, including hard labour, skilled work, the use of instruments and tools and shooting, of giving 6 mg of atropine sulphate by injection to twenty‐three adult male volunteers.
. Impairment of performance was seen in these tasks under the influence of the drug, but this was statistically significant only in some of them.
. Drowsiness occurred in twenty‐one men and perceptual disorders were common, but two men were almost completely resistant to the effects of the drug.
. The implications of the therapeutic use of comparable doses of atropine are discussed.
Interaction between (±)‐amphetamine and atropine on the rat cardiovascular system
Authors: ALLAN DOROTHY , BAIRD J. R. C. , ELLIS KATHLEEN E. J. 
Published: July 2012

. The effects of atropine on the pithed rat blood pressure after (±)‐amphetamine depend on the pattern of the cardiovascular responses to the latter.
. If the pressor response to amphetamine is followed by oscillations of blood pressure and a reduction in pulse pressure or by a fall in blood pressure terminating in circulatory failure, atropine increases blood pressure, but if it is not followed by these patterns, atropine decreases blood pressure.
. The fall in blood pressure produced by atropine after amphetamine might be due to weak alpha‐adrenoceptor blockade.
A comparison of the anti‐arrhythmic actions of I.C.I. 50172 and (—)‐propranolol and their effects on intracellular cardiac action potentials and other features of cardiac function
Authors: PAPP J. GY. , WILLIAMS E. M. VAUGHAN 
Published: July 2012

. I.C.I. 50172 had marked quinidine‐like effects on intracellular cardiac action potentials at concentrations above 20 mg/l. (6·61 × 10−5m). The rate of rise and overshoot of the action potential, conduction velocity and contractions were decreased. (–)‐Propranolol had similar effects at less than 1/30 this concentration.
. I.C.I. 50172 had 1/100 the activity of (–)‐propranolol as a local anaesthetic. Since this is also the ratio of their in vitro β‐receptor blocking activities, I.C.I. 50172 provides no net increase in specificity of β‐receptor blockade.
. In contrast, the in vivo activity of I.C.I. 50172 in protecting anaesthetized guinea‐pigs against ouabain‐induced ventricular fibrillation was 40% that of (–)‐propranolol.
. Structure‐activity relations of β‐receptor blocking drugs are discussed.
Effects of monoamine oxidase inhibitors on the hypothermia produced in cats by halothane
Authors: SUMMERS R. J. 
Published: July 2012

. In cats, the effects of intraperitoneal injections of four monoamine oxidase (MAO) inhibitors, tranylcypromine, pheniprazine, pargyline, and nialamide, were examined on rectal temperature and on the hypothermia during anaesthesia produced by a 2 hr period of halothane inhalation.
. A 2 hr period of halothane inhalation produced a steady fall in temperature amounting to between 2° and 3·5° C. After discontinuation of halothane inhalation, temperature quickly returned to the pre‐anaesthetic level but no pyrexia developed. A peculiar stiffness of the leg muscles occurred in several experiments either at the beginning of the inhalation or after its discontinuation.
. An injection of tranylcypromine (5 mg/kg) caused a rise in rectal temperature and prevented the hypothermia of halothane anaesthesia. This effect lasted for at least 4 hr; 20 hr after the injection, halothane again caused hypothermia.
. An injection of pheniprazine (10 mg/kg) usually caused a small rise in temperature which was not sustained. Pheniprazine not only prevented the hypothermia of halothane anaesthesia during the subsequent 20 hr, but during the first few hours after the injection halothane inhalation actually produced a steep rise in temperature.
. An injection of pargyline (50 mg/kg) had no effect on temperature but the hypothermia due to halothane inhalation was prevented 1 hr after the injection and attenuated after 20 hr. Injection of 200 mg/kg caused a steady rise in temperature which was accelerated when halothane was administered 1 hr later.
. An injection of nialamide (10, 25 or 50 mg/kg) had no immediate effect on temperature, but pyrexia developed overnight after the two larger doses. The effect on the hypothermia due to halothane inhalation was greater 20 hr after the injection than it was after 1 to 2 hr. Twenty hours after injection of the two larger doses, halothane no longer produced hypothermia but caused a lethal rise in temperature either during or after its inhalation.
. In rabbits, the effect on temperature of halothane inhalation varied. Either temperature rose slightly or it fell, but not as much as in cats. In one rabbit in which the inhalation had produced a transient rise, pyrexia developed 40 min after discontinuation of halothane.
Some properties of the denervated anterior gracilis muscle of the rat
Authors: TURKANIS S. A. 
Published: July 2012

. Microdrops of acetylcholine (ACh) were topically applied to denervated, mammalian skeletal muscle in vivo, and ACh‐evoked depolarization and contracture were recorded simultaneously.
. Contracture tension was directly proportional to the degree of ACh‐elicited depolarization.
. Atropine and (+)‐tubocurarine increased the amount of ACh required to produce a given amount of depolarization, but these anticholinergic agents did not alter the relationship between the degree of ACh‐evoked depolarization and contracture tension.
. Topically applied catecholamines did not produce either depolarization or contracture, despite the fact that parenterally administered catecholamines elicited both responses.