Posted by Rick on June 3, 2001, at 1:59:04
In reply to Re: Studies: New Celexa promising, posted by SLS on June 2, 2001, at 22:53:59
>Anyway, Sepracor and other drug manufacturers are pursuing refined versions (called ICEs - Improved Chemical Entities) of currently marketed antidepressants. Escitalopram (s-citalopram) is an example of one.
Interesting! I hope these trials are harbingers of major improvement in the med arsenal. Good observation re the Prozac trial. It's a shame that this may have been aborted needlessly.
> >Also, about a year ago, I read about testing on a new version of Valium without the side effects and dependence or addiction risks.
> Did this involve the identification of a benzodiazepine receptor domain subtype?I'm not sure what a "receptor domain subtype" is, but the prospects of no-sedation benzos *is* tied to Roche's apparent pinpointing of the key receptor for anxiolytic benefit. I originally read about this in small article in the medical briefs section of a daily newspaper. Immediately below is a more-detailed press release I found on Roche's website. (I simply went to www.roche.com and did a free-text search on Valium.)
Rick
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Roche - Media Release
Basel, 5. October 2000
Towards a Better Treatment of Anxiety
Molecular Target for Benzodiazepine Tranquilizers Identified
At a press conference held in Zurich today, a major scientific breakthrough was announced which sets the foundation for the development of improved drugs to treat anxiety disorders. Swiss scientists have identified the molecular target for the anxiolytic effect of benzodiazepine tranquilizers, including diazepam (VALIUM). This finding to which Roche researchers contributed is published in the October 6th issue of Science.The benzodiazepine drug class was discovered by Roche scientists in the late 1950s and benzodiazepines are now widely used to treat anxiety disorders. An estimated 10-15% of the adult population in the Western countries suffers from anxiety disorders. Thus, the discovery and development of novel, improved tranquilizers is addressing an important medical need.
In human and animal brain, inhibitory control of nerve cell activity is primarily mediated by the activation of widespread GABAA (gamma-aminobutyric acidA) receptors. Benzodiazepines act to facilitate the function of these GABAA receptors and thereby ease anxiety. Classical benzodiazepine drugs such as VALIUM interact indiscriminately with all benzodiazepine-sensitive GABAA receptor subtypes (alpha1, alpha2, alpha3 and alpha5). The focus of current investigations is the determination of the relative role of the subtype receptors in the therapeutic actions and side effects of the benzodiazepines.
Swiss scientists have now succeeded in identifying the receptor subtype which is the molecular target that mediates the anxiolytic effect of benzodiazepine tranquilizers. This scientific breakthrough was accomplished within a research programme which has been undertaken to silence each of these a subtype receptors in gene targeted mice generated in a collaborative effort between scientists at Roche, researchers at the Federal Institute of Technology in Zurich (ETHZ) and the University of Zurich. In the present study, two mouse lines were compared in which one GABAA receptor subtype, either the alpha2 or alpha3 GABAA receptor, was rendered insensitive to diazepam. This was done by creating genetically altered mice which carry a variation, or so-called point mutation, in one of the subunits of the GABAA receptor. The results indicate that the anxiolytic action of diazepam in mice is selectively mediated by neurons carrying the alpha2 GABAA receptor localised in the limbic system, a brain area which is implicated in emotional stimulus processing of the anxiety response.
This study, together with previous investigations conducted by the research group of Prof. Hanns Möhler at the Federal Institute of Technology in Zurich (ETHZ) and the University of Zurich together with Roche scientists, points the way to designing selective anxiolytic drugs targeted to alpha2 containing GABAA receptors thereby creating more selective tranquilizers lacking undesired effects such as sedation.
All trademarks used or mentioned in this release are legally protected.
(c) 2000 F. Hoffmann-La Roche Ltd
poster:Rick
thread:64685
URL: http://www.dr-bob.org/babble/20010530/msgs/65224.html