Effects of perospirone (SM-9018), a potential atypical neuroleptic, on dopamine D1 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 D2 blocking actions, and of haloperidol (HAL) on dopamine D1 receptor-mediated vacuous chewing movement (VCM) in rats. A selective D1 agonist, SKF 38393 (SKF), markedly increased the incidence of VCM, which was blocked by SCH 23390 (a D1 antagonist) but not by sulpiride (a D2 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 D1 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 D1 receptor-mediated VCM under repeated administration, which may be related to the 5-HT2 blocking activity of perospirone.
Ohno
Y
Y
Research Center, Sumitomo Pharmaceuticals Co. Ltd., Osaka, Japan. ohno@sumitomopharm.co.jp
Ishida-Tokuda
K
K
Ishibashi
T
T
Nakamura
M
M
D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine / Q000633:toxicity; D000818:Animals; D014150:Antipsychotic Agents / Q000633:toxicity*; D001362:Avoidance Learning / Q000187:drug effects; D018491:Dopamine Agonists / Q000633:toxicity; D018492:Dopamine Antagonists / Q000633:toxicity*; D004409:Dyskinesia, Drug-Induced / Q000503:physiopathology*; D006220:Haloperidol / Q000633:toxicity; D007211:Indoles / Q000633:toxicity*; D054833:Isoindoles; D008297:Male; D008409:Mastication / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017447:Receptors, Dopamine D1 / Q000187:drug effects; D017448:Receptors, Dopamine D2 / Q000187:drug effects; D011985:Receptors, Serotonin / Q000187:drug effects; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists / Q000633:toxicity*; D013844:Thiazoles / Q000633:toxicity*
D014150:Antipsychotic Agents; D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D007211:Indoles; D054833:Isoindoles; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin; D044263:Receptors, Serotonin, 5-HT1; D012702:Serotonin Antagonists; D013844:Thiazoles; D015647:2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine; D006220:Haloperidol; C065533:perospirone