Effects of Perospirone (SM-9018), a Potential Atypical Neuroleptic, on Dopamine D 1 Receptor-Mediated Vacuous Chewing Movement in Rats: A Role of 5-HT 2 Receptor Blocking Activity

• Published in: Pharmacology, biochemistry and behavior Vol. 57; no. 4; pp. 889 - 895
• Main Authors: Ohno, Yukihiro, Ishida-Tokuda, Kumiko, Ishibashi, Tadashi, Nakamura, Mitsutaka
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 1997
• Subjects: 5-HT 2 receptors; D 1 receptors; Haloperidol; Neuroleptics; Perospirone (SM-9018); Tardive dyskinesia; Vacuous chewing movement; Perospirone (SM-9018); Neuroleptics; Vacuous chewing movement; D 1 receptors; 5-HT 2 receptors; Haloperidol; Tardive dyskinesia
• ISSN: 0091-3057; 1873-5177
• DOI: 10.1016/S0091-3057(96)00468-6

We compared the acute and subacute effects of perospirone (SM-9018), a novel neuroleptic with potent 5-HT 2 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-HT 2 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-HT 2 blocking activity of perospirone.