Posted by Snowie on October 15, 2000, at 6:57:06
In reply to Re: Benzo Research Phil, Noa, posted by medlib on October 15, 2000, at 0:20:55
Medlib--
Registration is a requirement for Medscape. I couldn't access Noa's article (I was too lazy to register), but here's your article for those who don't have access to Medscape. I had read it before, and it sounds very promising.
Snowie
GABA-A Alpha-2 Receptor Subunit Proposed as Target for Antianxiety Drugs
--------------------------------------------------WESTPORT, CT (Reuters Health) Oct 9 - The alpha-2 subtype of gamma-aminobutyric acid type A (GABA-A) receptors mediates the anxiety-relieving effects of benzodiazepines in mice, according to a report in the October 6th issue of Science.
The researchers explain that although they previously linked the sedative and amnesic properties of diazepam to alpha-1 GABA-A receptors, until now it was not possible to identify the GABA-A receptor subtypes that mediate the drug's anxiolytic effects.
Dr. Karin Low, currently at the University of California at San Diego, and colleagues studied the behavioral and physiological effects of diazepam-insensitive mutations in GABA-A receptor subtypes alpha-2 and alpha-3 in mice.
Diazepam-insensitive binding sites increased from 5% in wild-type mice to 17% in alpha-2 mutant mice and 11% in alpha-3 mutant mice, the authors report. The potentiation by diazepam of the normal electrophysiological response to GABA-A was diminished in cultured mouse hippocampal pyramidal cells bearing the alpha-2 mutation.
Diazepam's sedative, motor-impairing, and anticonvulsant effects were retained in both alpha-2 and alpha-3 mutant mice, the researchers note.
In two behavioral tests, alpha-2 mutant mice failed to show the anxiolytic-like effect of diazepam treatment, the investigators observed. Alpha-3 mutant mice and wild-type mice, in contrast, displayed the usual dose-dependent anxiolytic-like response to diazepam.
"The anxiolytic-like action of diazepam is selectively mediated by the enhancement of GABAergic transmission in a population of neurons expressing the alpha-2 GABA-A receptors, which represent only 15% of all diazepam-sensitive GABA-A receptors," the authors conclude. "Our findings indicate that the alpha-2 GABA-A receptors are highly specific targets for the development of future selective anxiolytic drugs."
Science 2000;290:131-134.
> Phil, Noa--
>
> I just came across another summary of the same article in a Medscape newsletter.
>
> http://psychiatry.medscape.com/reuters/prof/2000/10/10.09/20001006scie001.html
>
> Registration shouldn't be required to access this one, but it may not be quite as readable as the Science mag one. I don't know why the URL wouldn't hyperlink, but it can be copy/pasted.
>
> Info looks promising.--medlib
>
>
> >Phil, I just found the article about this research. It is in the current (October 6, 2000, vol 290) issue of Science. On page 23 there is a news article about it (for us lay folks) and on page 131 is the research report. I don't know about others, but I think this is big news. Here is the summary from the online site for Science magazine:
> >
> > NEUROSCIENCE:
> > A Possible Target for Better Benzodiazepines
> >
> > Laura Helmuth
> >
> > Pharmacologists have tried for years to distill the desirable effects of
> > benzodiazepines from the undesirable ones; now a team of neuroscientists has
> > shown that such a strategy could well succeed. Benzodiazepines work by
> > amplifying the action of the neurotransmitter GABA, the brain's main "off" switch,
> > and in work described on page 131, a group has pinpointed one particular
> > subtype of the GABA receptor as the source of benzodiazepines'
> > anxiety-reducing powers.
> >
> > The url for this summary is:
> >
> > http://www.sciencemag.org/cgi/content/summary/290/5489/23b?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=benzodiazepines++valium&searchid=QID_NOT_SET&stored_search=&FIRSTINDEX=&fdate=10/1/2000&tdate=10/31/2000
> >
> > Unfortunately, registration is required to get into their site, and a subscription is required to read the full text. I read the old fashioned way--at the good ole bricks and mortar public library.
poster:Snowie
thread:45948
URL: http://www.dr-bob.org/babble/20001012/msgs/46399.html