Neuroendocrine evidence for antagonism of serotonin and dopamine receptors by olanzapine (LY170053), an antipsychotic drug candidate.

Olanzapine, 2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno[2,3-B] [1,5]benzodiazepine (LY170053), antagonized the quipazine-induced elevation of serum corticosterone concentration in rats with an ED50 value of 0.57 mg/kg i.p. LY170053 was less potent in antagonizing the pergolide-induced elevation of serum corticosterone concentration in rats, and increases in corticosterone elicited by olanzapine alone at higher doses complicated the precise estimate of an ED50 value, which was approximately 3 mg/kg. These relative potencies in blocking quipazine and pergolide effects are taken as indices of antagonism of serotonin 5HT2 and of dopamine D2 receptors, respectively. Olanzapine is more potent than clozapine in blocking 5HT2 and D2 receptors, and its ability to block these receptors supports its possible usefulness as an antipsychotic drug.