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 D(2)/5-HT(2) 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-HT(1A)-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.[1]References
- Perospirone, a novel antipsychotic agent, hyperpolarizes rat dorsal raphe neurons via 5-HT1A receptor. Shiwa, T., Amano, T., Matsubayashi, H., Seki, T., Sasa, M., Sakai, N. J. Pharmacol. Sci. (2003) [Pubmed]
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