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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 9 of 9. This is the beginning of the thread.
Posted by noa on October 8, 2000, at 9:26:08
The Post had a small article about research (in Switzerland, I
believe) that could lead to anti-anxiety meds that address the
anxiety without the usual benzo side effects. Apparently, benzos
act upon four receptor subunits. So, they bred mice selectively
so that they had mice with all possible combos of responsive and
non-responsive subunits.Lo and behold, they discovered that it is only ONE of the four
affected subunits that is the one that causes the desired anti-
anxiety effect, and the mice with just that receptor subunit
working had none of the undesired (side) effects.THis is so cool, because now it is possible to create meds that do
what is needed without all the drowsiness, addictive potential,
etc. This could be a major turning point for millions of people!!
Posted by Phil on October 8, 2000, at 11:19:33
In reply to New Research on Antianxiety Medications (Benzos), posted by noa on October 8, 2000, at 9:26:08
That's good news, Noa. I'm starting to WORRY about the benzo part of my current cocktail..thought benzo's were supposed to help that! Go figure.
Phil
Posted by Noa on October 13, 2000, at 14:16:15
In reply to Re: New Research on Antianxiety Medications (Benzos), posted by Phil on October 8, 2000, at 11:19:33
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 BenzodiazepinesLaura 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:
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.
Posted by medlib on October 15, 2000, at 0:20:55
In reply to New Benzo Research-help minus sedation,addiction? » Phil , posted by Noa on October 13, 2000, at 14:16:15
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.
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.
Posted by medlib on October 15, 2000, at 18:33:19
In reply to Re: Benzo Research Phil, Noa » medlib, posted by Snowie on October 15, 2000, at 6:57:06
> 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.
Posted by noa on October 16, 2000, at 8:05:30
In reply to Thanks for the article! (np) » Snowie, posted by medlib on October 15, 2000, at 18:33:19
I hope this can be translated into a new line of meds real soon!
Posted by MarkinBoston on October 26, 2000, at 15:52:11
In reply to Re: Thanks ---isn't this cool?, posted by noa on October 16, 2000, at 8:05:30
> I hope this can be translated into a new line of meds real soon!
Count on it. There probably is already a company well along testing new patentable drugs based on this work long before it got published. Having a friend doing basic research at a university its all too often that lab directors (or friends of)have fingers in startups that coincidently develop products similar to the research from that director's lab.
Yeah, we'll see them and they will cost much more than benzo's. The greater safety is excellent for FDA approval and getting HMOs to pay the much higher prices. Pmeds are good profit makers for drug companies. High prices can be gotten away with because its still less expensive than hours and hours of therapy for a HMO.
Posted by S. Howard on October 29, 2000, at 1:25:34
In reply to Re: Thanks ---isn't this cool?, posted by MarkinBoston on October 26, 2000, at 15:52:11
Soon there may be drugs that enable people from Boston to pronounce their 'R's.-My In-laws are from Medfod
This is the end of the thread.
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