COMPARATIVE STUDIES ON THE EEG EFFECTS OF IMIPRAMINE AND CHLORPROMAZINE IN THE NORMAL AND RESERPINIZED RABBITS

摘要

References(36) Among a series of clinically available psychopharmacological agents chlorpromazine is known to be effective against the reactive or neurotic depressive disorders with little effect on the endogenous depression, while imipramine is described to be very effective against the endogenous disorders by activating the psychic processes rather than by sedating. Therefore, the comparison of the pharmacological effects of both agents has been a matter of much concern. Domenjoz and Theobald (1) have found little difference in the anti-acetylcholine, anti-barium chloride and anti-serotonin potencies between imipramine and chlorpromazine using the isolated small intestine. However, relative anti-histamine potency appeared to depend upon the experimental preparations used. Chlorpromazine proved more potent against histamine on the isolated ileum, while imipramine was more potent in antagonizing the effects of histamine on the ear vessels of rabbits. Sigg (2) has reported that both agents prolong the barbiturate sleep and alcohol sedation and depress the motor activity in mice and the conditioned avoidance response in rats, though chlorpromazine is more potent than imipramine in all respects. Further, he has shown the difference between both agents in the peripheral effects; imipramine potentiates the contractile responses of the nictitating membrane of cats to stimulation of the cervical sympathetic nerve and to exogenously administered noradrenaline or serotonin, but chlorpromazine suppresses either response. He has also described the divergency in the effects of both agents on the pressor responses of dogs to noradrenaline. Thoenen et al. (3, 4) have shown the potentiating effect of imipramine on the contractile response and noradrenaline output of the isolated perfused spleen of cats to sympathetic stimulation, in contrast to the suppressing effect of chlorpromazine. Axelrod et al. (5, 6) have demonstrated that imipramine inhibits the uptake of tritiated noradrenaline in the brain of intact rats, while chlorpromazine does not. It is well known that the effects of imipramine and chlorpromazine on the spontaneous EEG coincide well; both agents produce the resting pattern intermingled with the spindle bursts. The depletion of monoamines in the brain by reserpine has widely been demonstrated in association with the simultaneous development of sedation. The antagonistic effect of imipramine against the depressed behavior caused by reserpine in the experimental animals has also been discussed in relation with the role of endogenous monoamines in the central nervous system. In the present experiments, the effects of imipramine and chlorpromazine on the cortical and hippocampal EEG were comparatively studied in the intact and reserpinized rabbits.