Pharmacological evaluation of minaprine dihydrochloride, a new psychotropic drug.

Minaprine (3-[2-morpholino-ethlamino]-4-methyl-6-phenyl-pyridazine dihydrochloride; 30038CM; trade name in France: Cantor) is a new psychotropic drug. The therapeutic profile of minaprine differs from that of other known psychotropic agents; in man the drug antagonizes the "inhibitory syndrome" characterized by decreased spontaneous activity, reduction in basic drives, slowed thoughts, feelings of tiredness and social withdrawal. Preliminary clinical trials have indicated that minaprine may also be effective in certain depressive states. This finding prompted us to study the effects of minaprine in animal models for depression. Like most antidepressants minaprine antagonizes behavioral despair, but the effect exhibits a slow onset and maximal activity is reached 24 h after administration. Minaprine also antagonizes reserpine-induced ptosis, this effect has a rapid onset, and is long-lasting. In contrast, minaprine poorly antagonizes reserpine-induced hypothermia. Unlike most antidepressants minaprine does not potentiate yohimbine-induced lethality. Minaprine potently antagonizes prochlorperazine-induced catalepsy in rats and potentiates amphetamine-induced stereotyped behavior, suggesting that the drug may enhance dopaminergic transmission. Finally, minaprine does not antagonize either oxotremorine-induced tremors or physiostigmine-induced lethality. Taken together the results of the present study indicate that minaprine is active on certain, but not all, animal models for depression and suggest the drug may have a potential clinical utility in the treatment of human depressions.

Cilioinhibitory effect of phenothiazines in vitro and its antagonism by Ca++.

The inhibition of ciliary beating in vitro by physiologic concentrations of chlorpromazine (CPZ) and prochlorperazine (PCP) was demonstrated in two experimental systems. CPZ had a greater cilioinhibitory effect than PCP on the rotational velocity of tissue explants from the frog palate in amphibian Ringers, and on the frequency of ciliary beating in rat tracheal rings in culture medium. Addition of calcium acetate in equal molarity to CPZ, within a time limit dependent on the drug concentration, reversed this inhibition, while dibutyryl cyclic AMP did not. Simultaneous addition of Ca++ and CPZ slowed down, but did not stop, this ciliostasis, while priming with Ca++ or cyclic AMP prior to drug addition had less of an effect. These data lend support to a prevalent theory that CPZ exerts its actions by displacing calcium ions from membrane sites.

Prochlorperazine in childhood: side-effects.

The side-effects of prochlorperazine (CompazineR StemetilR) were traced in thirty-six children up to the age of sixteen years and compared with those collected from literature. These side-effects appeared to be predominantly neurological and were independent of the dosage. Impaired consciousness, dyskinesia, pyramidal signs and hypertonus were the main neurological manifestations. Dyskinesia was the most frequent sign. These side-effects disappear spontaneously after discontinuation of the drug. Instant cure can be acquired by intra-muscular administration of orphenadrine (DisipalR).

Effects of clozapine on cerebral catecholaminergic neurone systems.

1. Clozapine, a dibenzodiazepine derivative claimed to possess antipsychotic properties in man without producing extrapyramidal disorders, greatly increased the turnover of cerebral dopamine in the rat.2. The drug itself was virtually devoid of cataleptigenic activity in rats; however, it antagonized prochlorperazine-induced catalepsy.3. It is proposed that clozapine causes a blockade of striatal dopamine receptors which is of the surmountable type in contrast to that produced by cataleptigenic neuroleptics. In addition, clozapine may also increase the turnover of cerebral noradrenaline.