Effects of subchronic treatments with SM-9018, a novel 5-HT2 and D2 antagonist, on dopamine and 5-HT receptors in rats.
1. Receptor binding and behavioral studies were performed to compare the effects of subchronic treatments with SM-9018, a novel 5-HT2 and D2 antagonist, and with haloperidol (HAL) on dopamine and 5-HT receptors in rats. 2. SM-9018 treatment (10 mg/kg/day p.o.) for 2 weeks did not significantly change the density (Bmax) of striatal D2 receptors or the incidence of stereotyped behavior induced by apomorphine (APO). By contrast, HAL treatment (3 mg/kg/day p.o., for 2 weeks) significantly increased the D2 receptor density by about 55% and markedly enhanced the behavioral response to APO. 3. The density of 5-HT2 receptors in the cerebral cortex was significantly reduced (about 20%) by SM-9018 treatment without being affected by HAL. However, the hyperthermic response of rats to p-chloroamphetamine (p-CAMP, a putative 5-HT releaser) was unaltered by either treatment. 4. Neither SM-9018 nor HAL treatment changed the density of 5-HT1A receptors in the hippocampus. 5. These findings suggest that SM-9018 is weaker than HAL in inducing up-regulation and supersensitivity of the striatal D2 receptors after the subchronic treatment.
Ohno
Y
Y
Discovery Research Laboratories II, Research Center, Sumitomo Pharmaceuticals Co., Ltd., Osaka, Japan.
Ishibashi
T
T
Okada
K
K
Ishida
K
K
Nakamura
M
M
D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001667:Binding, Competitive; D006220:Haloperidol / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology*; D054833:Isoindoles; D008297:Male; D020891:Raclopride; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000187:drug effects*; D011985:Receptors, Serotonin / Q000187:drug effects*; D012457:Salicylamides / Q000494:pharmacology; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013844:Thiazoles / Q000494:pharmacology*; D015854:Up-Regulation
D014150:Antipsychotic Agents; D007211:Indoles; D054833:Isoindoles; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin; D012457:Salicylamides; D012702:Serotonin Antagonists; D013844:Thiazoles; D020891:Raclopride; D006220:Haloperidol; C065533:perospirone