This Article Full Text (OnlineFirst PDF) All Versions of this Article: 0269881107082944v1 23/1/65    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Shahid, M. Articles by Wong, E. H. F. Search for Related Content PubMed PubMed Citation Articles by Shahid, M. Articles by Wong, E. H. F. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB CLOZAPINE Social Bookmarking                         What's this?

Asenapine: a novel psychopharmacologicagent with a unique human receptor signature

¹ Organon Laboratories Ltd, Newhouse, Lanarkshire ML1 5SH, UK.
² Pfizer Global R&D, 2800 Plymouth Road, Ann Arbor, MI 48105, USA..
³ Pfizer Global R&D, 2800 Plymouth Road, Ann Arbor, MI 48105, USA.

^* To whom correspondence should be addressed.

	Abstract

Asenapine is a novel psychopharmacologic agent under development forthe treatment of schizophrenia and bipolar disorder. We determinedand compared the human receptor binding affinities and functionalcharacteristics of asenapine and several antipsychotic drugs. Compoundswere tested under comparable assay conditions using cloned humanreceptors. In comparison with the antipsychotics, asenapine showed highaffinity and a different rank order of binding affinities (pKi) for serotoninreceptors (5–HT1A [8.6], 5–HT1B [8.4], 5–HT2A [10.2], 5–HT2B [9.8],5–HT2C [10.5], 5–HT5 [8.8], 5–HT6 [9.6] and 5–HT7 [9.9]), adrenoceptors(1 [8.9],2A [8.9], 2B [9.5] and 2C [8.9]), dopamine receptors(D1 [8.9], D2 [8.9], D3 [9.4] and D4 [9.0]) and histamine receptors(H1 [9.0] and H2 [8.2]). It had much lower affinity (pKi<5) formuscarinic receptors and was the only agent with affinity for H2 receptors.Relative to its D2 receptor affinity, asenapine had a higher affinity for5–HT2C, 5–HT2A, 5–HT2B, 5–HT7, 5–HT6,2B and D3 receptors, suggestingstronger engagement of these targets at therapeutic doses. Asenapinebehaved as a potent antagonist (pKB) at 5–HT1A (7.4), 5–HT1B (8.1),5–HT2A (9.0), 5–HT2B (9.3), 5–HT2C (9.0), 5–HT6 (8.0), 5–HT7 (8.5), D2(9.1), D3 (9.1), 2A (7.3),2B (8.3), 2C (6.8) and H1 (8.4) receptors.These functional effects differed from those of risperidone (pKB5 for5–HT6) and olanzapine (pKB <5 for 5–HT1A and 2). Our results indicatethat asenapine has a unique human receptor signature, with bindingaffinity and antagonistic properties that differ appreciably from thoseof antipsychotic drugs.

Key Words: asenapine, bipolar disorder, human receptor, affinity, schizophreniaCorresponding author:

First published on February 28, 2008, doi:10.1177/0269881107082944

Journal of Psychopharmacology 2009;23:65.

A more recent version of this article appeared on January 1, 2009


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				S. Chapel, M. M. Hutmacher, G. Haig, H. Bockbrader, R. de Greef, S. H. Preskorn, and R. L. Lalonde Exposure-Response Analysis in Patients With Schizophrenia to Assess the Effect of Asenapine on QTc Prolongation J. Clin. Pharmacol., November 1, 2009; 49(11): 1297 - 1308. [Abstract] [Full Text] [PDF]