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Pharmacological Properties of DOV 315,090, an Ocinaplon Metabolite

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dc.contributor.author Berezhnoy, Dmytro en_US
dc.contributor.author Gravielle, Maria C en_US
dc.contributor.author Downing, Scott en_US
dc.contributor.author Kostakis, Emmanuel en_US
dc.contributor.author Basile, Anthony S en_US
dc.contributor.author Skolnick, Phil en_US
dc.contributor.author Gibbs, Terrell T en_US
dc.contributor.author Farb, David H en_US
dc.date.accessioned 2012-01-12T16:45:26Z
dc.date.available 2012-01-12T16:45:26Z
dc.date.copyright 2008 en_US
dc.date.issued 2008-6-13 en_US
dc.identifier.citation Berezhnoy, Dmytro, Maria C Gravielle, Scott Downing, Emmanuel Kostakis, Anthony S Basile, Phil Skolnick, Terrell T Gibbs, David H Farb. "Pharmacological Properties of DOV 315,090, an ocinaplon metabolite" BMC Pharmacology 8:11. (2008) en_US
dc.identifier.issn 1471-2210 en_US
dc.identifier.uri http://hdl.handle.net/2144/3368
dc.description.abstract BACKGROUND. Compounds targeting the benzodiazepine binding site of the GABAA-R are widely prescribed for the treatment of anxiety disorders, epilepsy, and insomnia as well as for pre-anesthetic sedation and muscle relaxation. It has been hypothesized that these various pharmacological effects are mediated by different GABAA-R subtypes. If this hypothesis is correct, then it may be possible to develop compounds targeting particular GABAA-R subtypes as, for example, selective anxiolytics with a diminished side effect profile. The pyrazolo[1,5-a]-pyrimidine ocinaplon is anxioselective in both preclinical studies and in patients with generalized anxiety disorder, but does not exhibit the selectivity between α1/α2-containing receptors for an anxioselective that is predicted by studies using transgenic mice. RESULTS. We hypothesized that the pharmacological properties of ocinaplon in vivo might be influenced by an active biotransformation product with greater selectivity for the α2 subunit relative to α1. One hour after administration of ocinaplon, the plasma concentration of its primary biotransformation product, DOV 315,090, is 38% of the parent compound. The pharmacological properties of DOV 315,090 were assessed using radioligand binding studies and two-electrode voltage clamp electrophysiology. We report that DOV 315,090 possesses modulatory activity at GABAA-Rs, but that its selectivity profile is similar to that of ocinaplon. CONCLUSION. These findings imply that DOV 315,090 could contribute to the action of ocinaplon in vivo, but that the anxioselective properties of ocinaplon cannot be readily explained by a subtype selective effect/action of DOV 315,090. Further inquiry is required to identify the extent to which different subtypes are involved in the anxiolytic and other pharmacological effects of GABAA-R modulators. en_US
dc.description.sponsorship National Institute of Mental Health (R01MH049469) en_US
dc.language.iso en en_US
dc.publisher BioMed Central en_US
dc.rights Copyright 2008 Berezhnoy et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. en_US
dc.rights.uri http://creativecommons.org/licenses/by/2.0 en_US
dc.title Pharmacological Properties of DOV 315,090, an Ocinaplon Metabolite en_US
dc.type article en_US
dc.identifier.doi 10.1186/1471-2210-8-11 en_US
dc.identifier.pubmedid 18554397 en_US
dc.identifier.pmcid 2529273 en_US


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Copyright 2008 Berezhnoy et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Except where otherwise noted, this item's license is described as Copyright 2008 Berezhnoy et al; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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