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Biomedical subjects

R Chermat

Publications and source records attributed to R Chermat.

At least 37 records · Page 2Linked to original sources

Effects of drugs affecting the noradrenergic system on convulsions in the quaking mouse.

Handling-induced convulsions in the quaking mouse can be blocked by: phenobarbital, pentobarbital or phenytoin; postsynaptic alpha-adrenoceptor agonists (noradrenaline, phenylephrine, CRL 40028); presynaptic alpha-adrenoceptor blockers (yohimbine, mianserine); catecholamine liberating agent (amphetamine); noradrenaline reuptake inhibitors (cocaine, imipramine, desipramine). Moreover, the protective effect of yohimbine was antagonized by clonidine, prazosin or alpha-methylparatyrosine, and the protective effect of CRL 40028 was antagonized by prazosin but not by alpha-methyltyrosine. Drugs acting by other mechanisms (pilocarpine, atropine, trihexyphenidyl, (--)-5-HTP, methysergide, pimozide, clonidine, alpha-methyl DOPA, prazosin, isoprenaline, salbutamol) did not protect against convulsions. A slight protection was obtained with high doses of apomorphine and also with (+/-)-propranolol. This effect is probably not related to blockade of beta-adrenoceptors because the same effect was obtained with (+)propranolol. In young quaking mice, where susceptibility to convulsions is low, both postsynaptic alpha-adrenoceptor blockers and presynaptic alpha-adrenoceptor antagonist lowered the convulsive threshold. Thus, this seems to constitute an interesting model for the in vivo study of substances which affect the central alpha-adrenoceptors either pre- or postsynaptically.

Animals↗

[The new versus the old antidepressant drugs: a comparative study of their psychopharmacological profiles (author's transl)].

We studied 13 known or potential antidepressants, choosen in different pharmacological classes: desipramine, imipramine, nialamide, dexamphetamine, AHR 1118, amineptine, iprindole, mianserine, nomifensine, salbutamol, TRH viloxazine, zimelidine. Each of these compounds was studied on 8 psychopharmacological tests: motor activity, reserpine induced hypothermia, reserpine induced ptosis, oxotremorine induced hypothermia, oxotremorine induced tremors, high doses apomorphine induced hypothermia, potentiation of toxic effects of yohimbine, behavioural despair. Clinical active compounds are efficient on yohimbine test and at least on one model of hypothermia; with a few exceptions, easy to explain, substances with a clearly demonstrated antidepressant activity in human have some common effects; these common effects can be used to predict, from animal experiments, an antidepressant effect in man.

Animals↗

Oxolinic acid and diazepam: their reciprocal antagonism in rodents.

The stimulant effects of oxolinic acid were investigated in rats and mice. This drug, given orally, consistantly induced, in doses ranging from 16 to 256 mg.kg-1, locomotor stimulation and stereotyped behavior. These effects were antagonized by pimozide (1 mg.kg-1), alpha-methyltyrosine (64 mg.kg-1) or reserpine (4 mg.kg-1, 24 h before testing) pretreatment, suggesting a facilitatory role of oxolinic acid on catecholaminergic processes. Diazepam (4-16 mg.kg-1) reduced the stimulant effects induced by oxolinic acid but not those induced by amphetamine; oxolinic acid (8 mg.kg-1) markedly reduced the antipunishment effect elicited in rats by diazepam (2 mg.kg-1). Since benzodiazepines have been reported to enhance GABA functioning, these data suggest that oxolinic acid may impair GABA transmission. However, neither muscimol (0.5-1 mg.kg-1) or gamma-acetylenic-GABA (16-64 mg.kg-1) selectively reduced the stimulant effects elicited by oxolinic acid. Therefore, the possible facilitation exerted by this drug on catecholaminergic systems may not derive from the release of an inhibitory GABAergic control.

Animals↗

[Effects of four beta-blocking agents on some psychopharmacological tests in mice (author's transl)].

Common effects of four beta-adrenergic blocking drugs have been investigated in mice using classical and new psychopharmacological tests. Propranolol, alprenolol, practolol and penbutolol reduced the increase in locomotor activity produced by reserpine after MAO inhibition; they produce hypothermia when associated with amphetamine and they increase oxotremorine-induced hypothermia. Regarding these three tests the studied substances ranged themseleves in the same order of potency: penbutolol greater than propranolol greater than alprenolol greater than practolol. Propranolol and penbutolol decreased the toxicity provoked in crowded mice by amphetamine or by the association pargyline-reserpine; alprenolol and practolol did not. Propranolol, penbutolol and alprenolol antagonized the amphetamine-induced increase in motor activity; practolol did not. When used at doses for which d-l propranolol was active, the dextrogyre isomer of propranolol was without effect whatever the test studied. It is suggested that for the selection of a beta-blocking drug, regarding central effects in man, the tests described would deserve consideration.

Adrenergic beta-Antagonists↗

Amoxapine in experimental psychopharmacology: a neuroleptic or an antidepressant?

2-Chloro-11-(piperazinyl)dibenz[b,f][1,4]-oxazepine (amoxapine) gives an unusual spectrum in psychopharmacological tests. Many of its effects are similar to those of neuroleptics: sedation, decrease in motor activity, catalepsy (which is, however, qualitatively different from that induced by classical neuroleptics), transitory suppression of avoidance reaction, antagonism of amphetamine induced toxicity in crowded mice and inhibition of stereotyped behavior induced by amphetamine in rats, and antagonism to various effects of apomorphine (stereotyped behaviour in rats, climbing behaviour, stereotyped behaviour and hypothermia in mice). At similar doses which produce the above mentioned effects, amoxapine also shows effects atypical for a neuroleptic, but which are relatively characteristic of antidepressants: antagonism of prochlorperazine-induced catalepsy in rats, inhibition of reserpine induced hypothermia in mice and enhancement of yohimbine toxicity in mice. The profile of this substance does not facilitate the anticipation of therapeutic effects in humans.

Amoxapine↗

[Models of inhibition in animal behavior].

The concept of inhibition in psychopharmacology is discussed by presenting different models of behavioral inhibition in animals. The inhibitions induced by fear or anxiety appear as a result of punishment introduction into an unknown situation, frustration... These inhibitions are particularly sensitive to minor tranquilizers. The inhibitions induced by "fatigue" appear when avoidance situations continue for 24 hours or when a situation demands a marked increase of animal activity to obtain the same reward (food). These inhibitions are particularly sensitive to psychoanaleptics. The inhibition induced by placing a animal in an inescapable situation is particularly sensitive to antidepressants.

Animals↗

Interaction of atropine or methylatropinium with four effects of two cholinergic drugs.

In mice, pilocarpine - or oxotremorine - induced decrease in locomotor activity and increase of the reaction time to pain were antagonized by atropine and not by methylatropinium. Identical doses of atropine and methylatropinium suppressed the antagonism of the cholinergics towards reserpine-induced palpebral ptosis. Cholinergics-induced hypothermia was not clearly antagonized by atropine or methylatropinium.

Animals↗