title: Effect of novel atypical antipsychotic, blonanserin, on extracellular neurotransmitter level in rat prefrontal cortex.
abstract: To clarify the mechanisms of action of blonanserin, an atypical antipsychotic drug, we studied the effects of systemic administration of blonanserin and risperidone on extracellular levels of norepinephrine, dopamine, serotonin, GABA and glutamate in the medial prefrontal cortex using microdialysis, and neuronal firing in the ventral tegmental area, locus coeruleus, dorsal raphe nucleus and mediodorsal thalamic nucleus using radiotelemetry. The binding affinities of blonanserin to D(2) and 5-HT(2A) receptors in the rat brain were confirmed and found to be similar. Blonanserin transiently increased neuronal firing in locus coeruleus and ventral tegmental area but not in dorsal raphe nucleus or mediodorsal thalamic nucleus, whereas risperidone increased the firing in locus coeruleus, ventral tegmental area and dorsal raphe nucleus but not in mediodorsal thalamic nucleus. Blonanserin persistently increased frontal extracellular levels of norepinephrine and dopamine but not serotonin, GABA or glutamate, whereas risperidone persistently increased those of norepinephrine, dopamine and serotonin but not GABA or glutamate. These results suggest a pharmacological correlation between the stimulatory effects of these antipsychotics on frontal monoamine release and neuronal activity in monoaminergic nuclei. Inhibition of the α(2) adrenoceptor increased extracellular monoamine levels and enhanced blonanserin-induced increase in extracellular serotonin level. These results indicated that the combination of antagonism of D(2) and 5-HT(2A) receptors contribute to the rise in extracellular levels of norepinephrine and dopamine, and that α(2) adrenoceptors play important roles in frontal serotonin release. They also suggest that blonanserin-induced activation of monoaminergic transmission could be, at least partially, involved in atypical antipsychotic properties of blonanserin.
authors.affiliation: Department of Psychiatry, Division of Neuroscience, Graduate School of Medicine, Neuropharmacology Unit, Brain Science and Animal Model Research Center (BSAM), Mie University, 2-174 Edobashi, Tsu, Mie, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Ohoyama
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamamura
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Hamaguchi
authors.forename: Masanori
authors.initials: M
authors.lastname: Nakagawa
authors.forename: Eishi
authors.initials: E
authors.lastname: Motomura
authors.forename: Takashi
authors.initials: T
authors.lastname: Shiroyama
authors.forename: Hisashi
authors.initials: H
authors.lastname: Tanii
authors.forename: Motohiro
authors.initials: M
authors.lastname: Okada
mesh_terms: D000818:Animals; D014150:Antipsychotic Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D008297:Male; D017551:Microdialysis; D009638:Norepinephrine / Q000378:metabolism; D010879:Piperazines / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D017397:Prefrontal Cortex / Q000187:drug effects* / Q000378:metabolism; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D044402:Receptor, Serotonin, 5-HT2A / Q000187:drug effects / Q000378:metabolism; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism; D018967:Risperidone / Q000494:pharmacology; D013686:Telemetry
chemical_list: D014150:Antipsychotic Agents; D010879:Piperazines; D010880:Piperidines; D044402:Receptor, Serotonin, 5-HT2A; D018341:Receptors, Adrenergic, alpha-2; D017448:Receptors, Dopamine D2; C079310:blonanserin; D018967:Risperidone; D004298:Dopamine; D009638:Norepinephrine