The behavioral effects of lopramine [N-methyl-N-(4-chlorobenzoyl-methyl)-3-(10, ll-dihydro-5H-dibenz (b, f) azepin-5-yl) propylamine hydrochloride] were investigated in mice and rats and compared with those of amitriptyline and imipramine. Lopramine inhibited reserpine hypothermia and haloperidol catalepsy in mice and tetrabenazine ptosis in rats. In addition, the drug potentiated the effects of methamphetamine, and DOPA- or apomorphine-induced stereotypy in mice, whereas it suppressed muricide of the rat induced by either olfactory bulbcctomy or ∆9-tetrahydrocannabinol, similar to the responses seen with imipramine and amitriptyline. On the other hand, lopramine increased spontaneous motor activity and markedly potentiated methamphetamine hyperactivity. In contrast to imipramine and amitriptyline, lopramine failed to counteract both the lethal effect of physostigmine and oxotremorine tremor in mice, indicating that the drug had no central anticholinergic effect. Lopramine, even at such a large dose as 5,000 mg/kg p.o., caused neither impairment of coordinated motor activity nor muscle relaxation. It is concluded that lopramine is a new type of tricyclic antidepressant with extremely low toxicity and without central antichohnergic action.
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