[The biochemical effects of a new antidepressive, metapramine (RP 19560) on activity of the dopaminergic and cholinergic systems of the rat striatum].

Abstract

The effects of metapramine (R.P. 19,560) on dopaminergic and cholinergic activities were mainly studied in the rat striatum. Metapramine, contrarily to apomorphine, is devoid of in vitro affinity for dopamine receptors and does not modify in vivo, the utilisation of dopamine in the striatum. Moreover, metapramine does not modify the increase of dopamine utilisation induced by thioproperazine, a neuroleptic of the phenothiazine family. Consequently metapramine is devoid of direct or indirect effect on nigrostriatal dopaminergic system. Metapramine, like dopaminergic agonists, increases acetylcholine levels in the striatum. Moreover metapramine is inactive in cerebral cortex and hippocampus. Metapramine partly or completely antagonises the decrease of acetylcholine levels induced by two neuroleptics of the phenothiazine family (thioproperazine and prochlorperazine), by reserpine or an association of reserpine and alpha-methyl-p-tyrosine. Metapramine which possesses a clinical antidepressant efficacy could be indicated for correction of extra-pyramidal side effects induced by neuroleptics or observed in parkinsonism.