Effects of perospirone (SM-9018), a potential atypical neuroleptic, on dopamine D-1 receptor-mediated vacuous chewing movement in rats: A role of 5-HT2 receptor blocking activity

We compared the acute and subacute effects of perospirone (SM-9018), a novel neuroleptic with potent 5-HT2 and D-2 blocking actions, and of haloperidol (HAL) on dopamine D-1 receptor-mediated vacuous chewing movement (VCM) in rats. A selective D-1 agonist, SKF 38393 (SKF), markedly increased the incidence of VCM, which was blocked by SCH 23390 (a D-1 antagonist) but not by sulpiride (a D-2 antagonist). Perospirone and HAL inhibited the SKF-induced VCM in a dose-dependent manner. The potency of the inhibitory actions of perospirone was considerably weaker (about 30 times) than that of HAL despite their similar affinities for D-1 receptors. Subacute treatment with perospirone for 2 weeks failed to affect the behavioral sensitivity of rats to SKF. However, the HAL treatment markedly enhanced the incidence of the SKF-induced VCM. On the other hand, the selective 5-HT2 antagonists ritanserin and ketanserin significantly reduced the inhibitory actions of HAL and SCH 23390 on the SKF-induced VCM. In addition, combined treatment of ritanserin with HAL for 2 weeks abolished the enhancement of SKF-induced VCM by HAL treatment. These findings suggest that perospirone is weaker than HAL in altering the behavioral sensitivity of D-1 receptor-mediated VCM under repeated administration, which may be related to the 5-HT2 blocking activity of perospirone. (C) 1997 Elsevier Science Inc.