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dc.contributor.authorBerezhnoy, Dmytroen_US
dc.contributor.authorGravielle, Maria C.en_US
dc.contributor.authorDowning, Scotten_US
dc.contributor.authorKostakis, Emmanuelen_US
dc.contributor.authorBasile, Anthony S.en_US
dc.contributor.authorSkolnick, Philen_US
dc.contributor.authorGibbs, Terrell T.en_US
dc.contributor.authorFarb, David H.en_US
dc.date.accessioned2012-01-12T16:45:26Z
dc.date.available2012-01-12T16:45:26Z
dc.date.copyright2008
dc.date.issued2008-6-13
dc.identifier.citationBerezhnoy, 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)
dc.identifier.issn1471-2210
dc.identifier.urihttp://hdl.handle.net/2144/3368
dc.description.abstractBACKGROUND. 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.sponsorshipNational Institute of Mental Health (R01MH049469)en_US
dc.language.isoenen_US
dc.publisherBioMed Centralen_US
dc.rightsCopyright 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.urihttp://creativecommons.org/licenses/by/2.0
dc.titlePharmacological Properties of DOV 315,090, an Ocinaplon Metaboliteen_US
dc.typearticleen_US
dc.identifier.doi10.1186/1471-2210-8-11
dc.identifier.pubmedid18554397
dc.identifier.pmcid2529273


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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.