Perospirone, a Novel Antipsychotic Agent, Hyperpolarizes Rat Dorsal Raphe Neurons via 5-HT1A Receptor
ABSTRACT: 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...
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doaj-7be5b5f737984d3690e15fc8fa5280182020-11-25T01:27:37ZengElsevierJournal of Pharmacological Sciences1347-86132003-01-01931114117Perospirone, a Novel Antipsychotic Agent, Hyperpolarizes Rat Dorsal Raphe Neurons via 5-HT1A ReceptorTsuguka Shiwa0Taku Amano1Hiroaki Matsubayashi2Takahiro Seki3Masashi Sasa4Norio Sakai5Department of Molecular and Pharmacological Neuroscience, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, JapanDepartment of Molecular and Pharmacological Neuroscience, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, JapanDepartment of Molecular and Pharmacological Neuroscience, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, JapanDepartment of Molecular and Pharmacological Neuroscience, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, JapanDepartment of Molecular and Pharmacological Neuroscience, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, JapanDepartment of Molecular and Pharmacological Neuroscience, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, JapanABSTRACT: 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.http://www.sciencedirect.com/science/article/pii/S1347861319326222 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Tsuguka Shiwa Taku Amano Hiroaki Matsubayashi Takahiro Seki Masashi Sasa Norio Sakai |
spellingShingle |
Tsuguka Shiwa Taku Amano Hiroaki Matsubayashi Takahiro Seki Masashi Sasa Norio Sakai Perospirone, a Novel Antipsychotic Agent, Hyperpolarizes Rat Dorsal Raphe Neurons via 5-HT1A Receptor Journal of Pharmacological Sciences |
author_facet |
Tsuguka Shiwa Taku Amano Hiroaki Matsubayashi Takahiro Seki Masashi Sasa Norio Sakai |
author_sort |
Tsuguka Shiwa |
title |
Perospirone, a Novel Antipsychotic Agent, Hyperpolarizes Rat Dorsal Raphe Neurons via 5-HT1A Receptor |
title_short |
Perospirone, a Novel Antipsychotic Agent, Hyperpolarizes Rat Dorsal Raphe Neurons via 5-HT1A Receptor |
title_full |
Perospirone, a Novel Antipsychotic Agent, Hyperpolarizes Rat Dorsal Raphe Neurons via 5-HT1A Receptor |
title_fullStr |
Perospirone, a Novel Antipsychotic Agent, Hyperpolarizes Rat Dorsal Raphe Neurons via 5-HT1A Receptor |
title_full_unstemmed |
Perospirone, a Novel Antipsychotic Agent, Hyperpolarizes Rat Dorsal Raphe Neurons via 5-HT1A Receptor |
title_sort |
perospirone, a novel antipsychotic agent, hyperpolarizes rat dorsal raphe neurons via 5-ht1a receptor |
publisher |
Elsevier |
series |
Journal of Pharmacological Sciences |
issn |
1347-8613 |
publishDate |
2003-01-01 |
description |
ABSTRACT: 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. |
url |
http://www.sciencedirect.com/science/article/pii/S1347861319326222 |
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