Perospirone, a novel antipsychotic agent, hyperpolarizes rat dorsal raphe neurons via 5-HT1A receptor
Perospirone, a novel antipsychotic agent, hyperpolarizes rat dorsal raphe neurons via 5-HT1A receptor
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DOI：
10.1254/jphs.93.114
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发表时间：
2003-09-01
影响因子：
3.5
通讯作者：
Sakai, N
中科院分区：
文献类型：
--
作者：
Shiwa, T;Amano, T;Sakai, N
采用全细胞膜片钳技术研究了新型抗精神病药物cis-N-[4-[4-（1，2-苯并异唑-3-基）-1-哌嗪基]丁基]环己烷-1，2-二甲酰亚胺盐酸盐（perospirone）对大鼠中缝背核（dorsal raphe，DR）神经元的作用。应用浓度在10（-9）和10（-5）M之间的哌罗匹隆使膜电位超极化，并以浓度依赖性方式抑制DR神经元的自发动作电位。Perospirone对DR神经元的这种作用类似于典型的5 HT（1A）受体激动剂，包括8-OH-DPAT或坦度螺酮。此外，WAY 100635，一种5-HT 1A受体拮抗剂，抑制这种perospirone诱导的DR神经元的超极化，表明perospirone作为一种5-HT（1A）受体激动剂在生理上作用于DR神经元。这些结果提供了新的配置文件作为一种抗精神病药物哌罗匹隆。
To investigate the effect of cis-N-[4-[4-(1,2-benz-isozole-3-yl)-1-piperazinyl]butyl] cyclohexane-1,2-dicarboximide hydrochloride (perospirone), a novel antipsychotic agent with high affinities for D-2/5-HT2 receptors, on the rat dorsal raphe (DR) neurons, an electrophysiological study was performed using the tight-seal whole-cell patch-clamp technique. Applications of perospirone at the concentration between 10(-9) and 10(-5) M hyperpolarized the membrane potential and inhibited spontaneous action potentials of the DR neurons in a concentration-dependent manner. This effect of perospirone on DR neurons is similar to that of typical 5HT(1A)-receptor agonists, including 8-OH-DPAT or tandospirone. In addition, WAY100635, a 5-HT1A-receptor antagonist, inhibited this perospirone-induced hyperpolarization of DR neurons, suggesting that perospirone physiologically acts on DR neurons as a 5HT(1A)-receptor agonist. These results provide new profiles of perospirone as an antipsychotic drug.