ROXINDOLE, A POTENTIAL ANTIDEPRESSANT .1. EFFECT ON THE DOPAMINE SYSTEM

Roxindole (EMD 49980, nyl-1,2,3,6-tetrahydropyridyl(1))-butyl(1)]-indo le mesylate), a selective dopamine autoreceptor agonist and a potentia l antipsychotic drug, shows a clinical antidepressant efficacy. The pr esent paper examined the neuropharmacological profile of roxindole in rats (male Wistar) and mice (male Albino Swiss) in respect of its infl uence on dopamine system. Used in low doses, roxindole decreased the l ocomotor activity, but in higher ones it did not induce a locomotor hy peractivity or stereotypy, It antagonized the amphetamine-induced hype rlocomotion, the amphetamine- or apomorphine-induced stereotypy, apomo rphine climbing behaviour and reserpine-induced akinesia. The quinpiro le-induced hyperlocomotion was inhibited by roxindole. When given alon e, the drug in question, did not induce the catalepsy, but antagonized the catalepsy induced by haloperidol, spiperone and fluphenazine. The immobility time in the forced swimming test was reduced. Like typical antidepressants, roxindole given repeatedly (twice daily, 14 days) in creased the hyperlocomotion induced by D-amphetamine. The results desc ribed above indicate that roxindole may have an antidepressant and ant iparkinsonian activity and should be devoid of extrapyramidal side-eff ects.