The effect of maprotiline (N-methyl-9, 10-ethanoanthracene-9(10H)-propylamine) on animal behavior was investigated in mice and rats and compared with those of amitriptyline and imipramine. Maprotiline inhibited reserpine hypothermia in mice and tetrabenazine ptosis in rats, while it potentiated the effects of methamphetamine, L-DOPA and apomorphine in mice, in a similar manner to that of amitriptyline and imipramine. Maprotiline was more potent than amitriptyline and imipramine in antagonizing haloperidol-induced catalepsy as well as in suppressing muricide induced by either olfactory bulbectomy or delta-9-tetrahydrocannabinol in rats. Maprotiline potentiated anesthesia induced by thiopental or ether in mice to a lesser degree than did amitriptyline, and failed to counteract the lethal effect of physostigmine or oxotremorine tremor in mice, indicating that this drug has no central anti-cholinergic effect. Maprotiline markedly inhibited hyperemo tionality of the rat with either septal lesions or olfactory bulb ablations, suggesting that it does have a tranquilizing effect. Inhibition of conditioned avoidance response of the rat in shuttle box and reduction of methamphetamine group toxicity with maprotiline were similar to those with amitriptyline. Maprotiline exaggerated pentetrazol convulsion, decreased muscle tone and impaired coordinated motor activity in mice to a much lesser degree than amitriptyline and imipramine. LD50 of maprotiline was approximately twice that of imipramine and three times that of amitriptyline. These results indicate that maprotiline is a new type of antidepressant, has a low toxicity and shares both potent antidepressant and some tranquilizing effect, without possessing central anticholinergic action.
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