The central anti-serotonin activity of zotepine, a new neuroleptic, in rats.

Abstract

Abstract-2-Chloro-1

Effect of zotepine on fenfluramine-induced hyperthermia in rats.

“…In any case, zotepine had a more potent anti -serotonergic activity than clozapine, spiroperidol or oxypertine which are reported to have more potent anti-serotonergic activity than known neuroleptics or to be more anti serotonergic than anti-dopaminergic (9)(10)(11). In addition to the present results and those of our previous report (5), it is clear that zotepine has the most potent anti-sero tonergic activity of the known neuroleptics. Clozapine is reported to cause fewer extra pyramidal symptoms (9), and spiroperidol and oxypertine are reported to be effective on syndromes on which haloperidol is ineffective (12).…”

“…Fenfluramine is known to induce hyper thermia in rats by mediation of central serotonin in a warm environment (25-28'C) (5)(6)(7)(8)(9). In the present study, rats with fen fluramine-induced hyperthermia were used to investigate the anti-serotonergic activity of zotepine, and it was compared with clozapine, spiroperidol and oxypertine which are reported to have potent anti-serotonergic activity rather than anti -dopami nergic activity (9)(10)(11).…”

“…In animal models, zotepine is also reported to have a potent anti-serotonergic as well as anti-dopaminergic activity (4,5). Fenfluramine is known to induce hyper thermia in rats by mediation of central serotonin in a warm environment (25-28'C) (5)(6)(7)(8)(9).…”

Effect of zotepine on head-twitch induced by L-5-Hydroxytryptophan,mescaline and 2,5-Dimethoxy-4-methylamphetamine in mice and rats.

“…Uchida et al (1) have reported that zotepine exerts its neuroleptic effects mainly through anti-dopaminergic activity. Shimomura et al (2) have shown that zotepine is a unique neuroleptic with potent central anti serotonergic activity. L-5-hydroxytryptophan (L-5HTP), some hallucinogens and benzodi azepines can induce head-twitch in animals (3)(4)(5)(6)(7)(8).…”

Two case studies of hypothermia induced by an increased dosage of zotepine in a combination therapy

“…Long‐term administration of zotepine may accelerate the metabolism of dopamine and norepinephrine 6 by the feedback mechanism from the post‐receptor site to the synthesis site of dopamine and norepinephrine in the presynaptic area, due to suppressed neurotransmission by the drug. Zotepine also suppresses the central serotonin transmission system in chronic use 7 . Therefore both chronic suppression of the 5‐HT transmission system and an increased metabolism of dopamine and norepinephrine may decrease body temperature.…”