Effect of zotepine and various drugs on apomorphine- and methamphetamine-induced rotational behaviour in rats with unilateral lesions of the substantia nigra.

The effect of zotepine (2-chloro-11-(2-dimethyl-aminoethoxy) dibenzo [b, f] thiepin), a new neuroleptic, and other neuroleptics, minor tranquilizers, antidepressants, anticholinergic drugs, antihistamine drugs, antiparkinsonian drugs, alpha-, beta-adrenergic blocking agents, hypnotics and central muscle relaxants on apomorphine (APM)- and methamphetamine (MAP)-induced rotational behaviour was investigated in rats with unilateral lesions of the substantia nigra. Only the neuroleptics dose-dependently depressed both rotational behaviours. The minor tranquilizers also depressed both behaviours, but their effect was non-specific. The neuroleptics could be divided into two groups according to their relative effect on the APM- and MAP-induced rotational behaviour. The high-ratio group (fluphenazine, haloperidol, perphenazine, pimozide and zotepine) depressed the MAP-induced rotational behaviour more strongly than the APM-induced one, whereas the depressive effect of the low-ratio group (chlorpromazine, levomepromazine, thioridazine and clozapine) was the reverse. Zotepine, while belonging to the high-ratio group, was markedly lower in ratio than the other neuroleptics in this group. The correlation between the different effect of the two groups of neuroleptics and their clinical effect is discussed.