From: bwhite@oucsace.cs.ohiou.edu (William E. White )
Newsgroups: sci.med
Subject: Re: 5-HT1A Agonist Anxiolytics (was Re: Xanax...)
Date: 11 Jan 93 16:55:01 GMT
Organization: Ohio University, Computer Science Department

In article <szikopou.726714815@cunews> szikopou@alfred.carleton.ca (Steven Zikopoulos) writes:
>In <1993Jan10.225201.15384@oucsace.cs.ohiou.edu> bwhite@oucsace.cs.ohiou.edu (William E. White ) writes:
>
>I agree.  I'm sure you're aware that individuals who respond best to
>anxiolytic medication are also those individuals who are more likely
>to show placebo effect.

Yes, that's true; still, I would imagine anxiolytics have been shown
to be better than placebo?

>>Imipramine for anxiety?  Yowch!  Sorta the shotgun effect; maybe what we
>>need is a rifle instead?  I saw some interesting results on 5HT1a agonists
>>as antianxiety drugs -- very good results, not always quite so powerful
>>as benzodiazepines, but with a *lot* fewer side effects (and given the
>>specificity, probably much fewer side effects than fluoxetine, and heaven
>>knows fewer than a MAOI.  Besides, cheese is good food).  Look in MEDLINE
>>for references -- hopefully 5HT1a agonists will turn out to be as good as
>>they look on paper .

>Your comments with respect to the efficacy of 5HT1a agonists leaves me
>a bit confused.  One common 'side' effect (come on an effect's an
>effect) obsrved in people taking is an INCREASE in aniREASE or
>exacerbation of already existing anxiety.  As far as I know,
>fluoxetine pots serotonin activity by blocking reup and nptake--which
>is not the same as stimulating 5HT recetors with an agent

Yes, fluoxetine is a reuptake inhibitor; the end result is not the same,
of course, as a selective 5HT agonist.  I don't know whether 5HT1A receptor
downregulation is the mechanism of antidepressants or not.


>I'll ask
>ask anyway.how can something which potentiaiates 5HT activity be an
>anxiolytic when (in the case of fluoxetine at lea we have evidence of
>5HT potentiating agenincreasing anxiety?

It was my understanding that at partial agonist levels, 5HT1a agonists
were anxiolytic, whereas at full agonist levels they had the opposite
effect (I could easily be wrong on this).  Furthermore, fluoxetine
affects all 5HT receptors; this could easily have a different effect
than a specific agonist or antagonist.

>What agents were they? I'm interested.  I hope you're not talking
>about Bupirone because it also mediates DA activity.

Yes, but is this through activation of 5HT1A receptors or is it a direct
agonist effect?  One piece of research I saw indicated that 5HT1A agonists
tended to be beta-adrenergic antagonists [SO: Mol-Pharmacol 1992 Apr; 41(4)
695-698; AU: Guam-XM; Peroutka-SJ; Kobilka-BK].  This may also complicate
matters.

In addition to buspirone, NDO008 (3-dipropyl-amino-5-hydrochromar) and 
in general aryl-piperazines show anxiolytic activity in rats (of course,
in the real world, rodent anxiety isn't that big of a concern as the
anxiety of humans).
I'm curious how more potent 5HT1A agonists (e.g., indolodioxanes) will
act; I'm also curious to see what the behavioural effects of S14671 (a
very potent 5HT1A agonist, as well as a 5HT1C/5HT2 antagonist) will be
[SO: J-Pharmacol-Exp-Ther. 1992 Aug; 262(2):451-63  AU: Millan-MJ; 
Rivet-JM; Canton-H; Lejeune-F; Bervoets-K; Brocco-M; Gobert-A; ...]


>Your discussion also talks of anxiety as something that is independent
>of depre  Most cases of depresssion are mixed. (anxiety and depression)

That's true; I was simply considering anxiety without depression, not
necessarily the other way around; even then it was probably a mistake
to think of the two as linearly independent when they are, in all
likelihood, mediated by the same systems.
In reality, I'm way out of my field; I've tried to keep up on 
serotoninergic drugs (of the antidepressant variety, not the 
hallucinogenic) due to personal interest in the workings of endogenous
depression, but that's about it.


>Forason the net's not cooperating with me right now, so I'dow so I'd
>better sign off.
>Steven Zikopoulos
>Carleton University
>szikopou@ccs.carleton.ca

>P.S. It always looks better on paper!

Very true.

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