Three different aspects of the psychopharmacological activity of the antidepressant maprotiline were investigated: its influence on serotoninergic functions the effects produced by chronic treatment its central nervous depressant and anxiolytic properties. Study of the effects of maprotiline on 5-HTP-induced head-twitch in mice pre-treated with pargyline or on hyperpyrexia in rats provided no evidence that the drug interferes with serotonin-mediated functions in the central nervous system even after quite high doses. These findings corroborate the results of extensive neurobiochemical investigations, which failed to demonstrate any influence of maprotiline on the metabolism of serotonin. Chronic studies showed that classical effects of maprotiline such as antagonism against reserpine-induced ptosis or tetrabenazine-induced catalepsy do not change in their intensity after daily administration of the drugs in a dose of 30 mg/kg p.o.for 11 days. A new component of the action of the compound, not detectable after one single dose, seems to appear, however, after repeated treatment (8 days). This effect is manifested in the restoration of conditioned avoidance behaviour after its suppression by pre-treatment with reserpine. The same effect is produced by imipramine. It is suggested that this restorative effect may be due to an additional activation of the dopaminergic nervous system and may have a bearing on the appearance of clinical antidepressant effects. Maprotiline was found to potentiate central nervous depressant effects of drugs like chlorpromazine, phenobarbitone and propranolol. This affords further confirmation that, in addition to its antidepressant qualities, it possesses sedative actions. An anxiolytic component was also demonstrated in rats in which maprotiline suppressed the conditioned, fear-induced rise in body-temperature.
Reduction of conditioned avoidance via contingency reversal
