Possible relationship between antimanic effect and activity of zotepine to 5HT1 receptor

Zotepine (ZTP), synthesized by Fujisawa Pharmaceutical Co., Ltd. for possible use as an antipsychotic drug, clinically features a very rapid and potent antimanic effect. To elucidate the psychopharmacological mechanisms of zotepine, we have attempted to measure the potency of ZTP compared with other neuroleptic drugs in competing for binding sites in the brain associated with dopamine, serotonin (5-HT1, 5-HT2), noradrenaline (NA) and acetylcholine. Zotepine was found to have the most potent activity to the 5HT1 receptor among the test drugs. Chlorpromazine and thioridazine, which belong to phenothiazines and clinically have less potent antimanic effect, shared ZTP's potent activity to the NA receptor, while they were less potent than ZTP in activity to the 5HT1 receptor. These results show that the activity of the drugs to the 5HT1 receptor may be associated with the antimanic effect.