Blonanserin, a novel atypical antipsychotic agent not actively transported as substrate by P-glycoprotein

Progress in Neuro-psychopharmacology & Biological Psychiatry
Tomoko InoueNoboru Yamaguchi

Abstract

Although blonanserin, a novel atypical antipsychotic agent with dopamine D(2)/serotonin 5-HT(2A) antagonistic properties, displays good brain distribution, the mechanism of this distribution has not been clarified. P-glycoprotein [(P-gp) or multidrug resistance protein 1 (MDR1)] is an efflux transporter expressed in the brain and plays an important role in limiting drug entry into the central nervous system (CNS). In particular, P-gp can affect the pharmacokinetics and efficacy of antipsychotics, and exacerbate or soothe their adverse effects. In this study, we conducted in vitro and in vivo experiments to determine whether blonanserin is a P-gp substrate. Risperidone and its active metabolite 9-hydroxyrisperidone, both of which are P-gp substrates, were used as reference drugs. Affinity of blonanserin, risperidone, and 9-hydroxyrisperidone for P-gp was evaluated by in vitro transcellular transport across LLC-PK1, human MDR1 cDNA-transfected LLC-PK1 (LLC-MDR1), and mouse Mdr1a cDNA-transfected LLC-PK1 (LLC-Mdr1a). In addition, pharmacokinetic parameters in the brain and plasma (B/P ratio) of test compounds were measured in mdr1a/1b knockout (KO) and wild-type (WT) mice. The results of in vitro experiments revealed that P-gp doe...Continue Reading

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Citations

Jun 15, 2013·Neuropsychiatric Disease and Treatment·Tomomi TenjinNoboru Yamaguchi
Jun 26, 2017·Psychotherapy and Psychosomatics·Guy ChouinardMasaomi Iyo
Sep 20, 2017·Journal of Psychopharmacology·Yusuke NakataMasaomi Iyo
Mar 9, 2017·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Natalia I BrzozowskaJonathon C Arnold
Jul 30, 2019·Clinical Psychopharmacology and Neuroscience : the Official Scientific Journal of the Korean College of Neuropsychopharmacology·Young Sup WooWon-Myong Bahk
Oct 5, 2017·European Journal of Clinical Pharmacology·De-Wei ShangYu-Guan Wen

Related Concepts

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Cell Line, Transformed
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Mice, Inbred Strains
Piperazines
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Pyrimidines
Antipsychotic Effect

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