Posted by Michael Bell on May 14, 2005, at 11:33:05
I was wondering what's been happening with Ocinaplon since the phase III trials started in November '04. Here's an article I found dated March 30, 2005. I believe the studies are supposed to finish by late 2006, but who knows?
A. Lippa *, P. Czobor *, J. Stark *, B. Beer *, E. Kostakis , M. Gravielle , S. Bandyopadhyay , S. J. Russek , T. T. Gibbs , D. H. Farb , and P. Skolnick *
*DOV Pharmaceutical, Inc., 433 Hackensack Avenue, Hackensack, NJ 07601; and Department of Pharmacology, Boston University School of Medicine, 80 East Concord Street, Boston, MA 02118Communicated by John W. Daly, National Institutes of Health, Bethesda, MD, March 30, 2005 (received for review November 8, 2004)
Benzodiazepines remain widely used for the treatment of anxiety disorders despite prominent, often limiting side effects including sedation, muscle relaxation, and ataxia. A compound producing a robust anxiolytic action comparable to benzodiazepines, but lacking these limiting side effects at therapeutic doses (an anxioselective agent), would represent an important advance in the treatment of generalized anxiety disorder, and perhaps other anxiety disorders. Here we report that the pyrazolo[1,5-a]-pyrimidine, ocinaplon, exhibits an anxioselective profile in both preclinical procedures and in patients with generalized anxiety disorder, the most common of the anxiety disorders. In rats, ocinaplon produces significant muscle relaxation, ataxia, and sedation only at doses >25-fold higher than the minimum effective dose (3.1 mg/kg) in the Vogel "conflict" test. This anticonflict effect is blocked by flumazenil (Ro 15-1788), indicating that like benzodiazepines, ocinaplon produces an anxiolytic action through allosteric modulation of GABAA receptors. Nonetheless, in eight recombinant GABAA receptor isoforms expressed in Xenopus oocytes, the potency and efficacy of ocinaplon to potentiate GABA responses varied with subunit composition not only in an absolute sense, but also relative to the prototypical benzodiazepine, diazepam. In a double blind, placebo controlled clinical trial, a 2-week regimen of ocinaplon (total daily dose of 180-240 mg) produced statistically significant reductions in the Hamilton rating scale for anxiety scores. In this study, the incidence of benzodiazepine-like side effects (e.g., sedation, dizziness) in ocinaplon-treated patients did not differ from placebo. These findings indicate that ocinaplon represents a unique approach both for the treatment and understanding of anxiety disorders.
poster:Michael Bell
thread:497685
URL: http://www.dr-bob.org/babble/20050510/msgs/497685.html