Posted by JohnX2 on March 3, 2002, at 23:09:10
In reply to Re: New Glaxo / Merck antidepressant, posted by SLS on March 3, 2002, at 19:33:15
Everything I read about pharmacology of
serotonergic systems seems to indicate that
you want to have an agonist at the 5ht-1a site
while antagonizing or down regulating the 5ht-2a site.Its believed from what I understand that a lot of SSRIs dont
respond because either they don't make it through
the first pass of downregulating the somotodendric
5ht-1a autorecptors (which would then increase
serotonin release, which pindolol is believed
to work at), or the medicine has difficulty
downregulating the postsynaptic receptors.Most SSRIS overtime downregulate 5ht-2 receptors
From "Essential Psychopharmacology" by Stephen
M. Stahl, 2nd edition. (a good book)
Figure 7-19
"Molecular stimulation of the 5ht-2a receptor
will alter the consequence of activating the
serotonin 5ht-1a receptor in a negative way and
reduce the gene expression of the 5ht-1a receptor
acting alone.....blah blah"Figure 7-21
Synergy between 5ht-1a stimulation and 5ht-2a
antagonism:
"The molecular consequence of 5ht-1a receptor
by disinhibition by 5ht-2a blockade is shown here,
namely enhanced gene expression...."So to beat around the bush, Stahl is suggesting
make a direct acting 5ht-1a agonist and combine
it with a 5ht-2a antagonist. i.e. something
like flibanserin. Maybe you can combine it
with a el-cheapo off patent SSRI to get an
enhanced effect.-John
> Here's a new one (sort of):
>
> http://pharmalicensing.com/news/adisp/982274821_3a8c5305199e4
>
> Excerpts:
>
> "GlaxoSmithKline plc and Merck KGaA have signed a worldwide
> development and commercialisation agreement for an antidepressant
> with a novel mechanism of action."
>
> "The compound, currently known as EMD 68843 or SB 659746-A, is in
> Phase II clinical development."
>
> "It combines the properties of a selective serotonin- reuptake
> inhibitor with those of a 5-HT1A partial agonist."
>
>
> Does anyone know how long it takes for a drug in phase-II trials to be approved?
>
> - Scott
poster:JohnX2
thread:95939
URL: http://www.dr-bob.org/babble/20020301/msgs/96256.html