Perospirone, a Novel Antipsychotic Agent, Hyperpolarizes Rat Dorsal Raphe Neurons via 5-HT1A Receptor

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 D2/5-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 5HT1A-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 5HT1A-receptor agonist. These results provide new profiles of perospirone as an antipsychotic drug.