Pharmacological action of zotepine and other antipsychotics on central 5-hydroxytryptamine receptor subtypes
Czyrak, A.; Skuza, G.; Rogóz, Z.; Frankiewicz, T.; Maj, J.
Arzneimittel-Forschung 44(2): 113-118
1994
ISSN/ISBN: 0004-4172 PMID: 7511901 Document Number: 432957
The effect of the atypical neuroleptic zotepine (CAS 26615-21-4), in comparison with clozapine, risperidone and haloperidol, on the responsiveness of different 5-hydroxytryptamine (5-HT-1) receptor subtypes to their agonists was examined in rats and mice. The above antipsychotics were investigated in the following behavioural tests: 8-OH-DPAT (8-hydroxy-dipropylaminotetralin)induced behavioural syndrome in rats, mCPP (mchlorophenylpiperazine)-induced hypothermia in mice anti mCPP-induced hypoactivity measured in the open field in rats. Zotepine, clozapine and haloperidol did not affect the behavioural syndrome induced by 8-OH- DPAT (the selective agonist of 5-HT-1A, receptor), only risperidone (used in higher doses) attenuated the effect of 8-OH-DPAT The mCPP-induced hypothermia in mice (a 5-HT-1B effect) was affected by neither zotepine nor clozapine, risperidone and haloperidol, all of them used in low doses which did not influence per se the body temperature of mice. All the tested antipsychotics given at high doses induced hypothermia in control mice; at the same time, zotepine, clozapine and risperidone attenuated the hypothermic effect of mCPP. mCPP decreases the exploratory activity of rats, this effect being considered to be mediated by 5-HT-1C receptors. The tested antipsychotics, used in low doses, influenced neither the exploratory activity nor the hypoactivity induced by mCPP When used at higher doses, they induced hypoactivity in control rats; the hypoactivity after joint administration of zotepine, risperidone or haloperidol and mCPP was significantly greater than after mCPP alone, whereas clozapine slightly attenuated the effect of mCPP. The obtained results indicate that zotepine did not affect the responsiveness of 5-HT-1A and 5-HT-1C receptors, but had a slight inhibitory effect on 5HT-1B receptor; the latter effect was shared by clozapine and risperidone, but not haloperidol. Risperidone showed a weak antagonistic effect on 5-HT-1A receptors, and clozapine-on 5-HT-1C ones.