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Re: selegiline, dopamine, social anxiety

Posted by jojo on July 19, 2000, at 18:48:12

In reply to Re: selegiline, dopamine, social anxiety » AndrewB, posted by Adam on July 19, 2000, at 0:17:10

> AndrewB,
> Oral selegiline is metabolized into l-amphetamine and l-methamphetamine (as well as desmethylselegiline, which has weak MAO-B inhibatory properties) at all doses, and the levels of those metabolites are related, obviously, to the levels of the parent compound.
> The l- enantiomers of amphetamine are, simplistically, "weaker" than their d- counterparts. I think it may be more accurate to say they are not very potent inhibitors of dopamine reuptake, but do have comparable effects on norepinephrine release, and I believe can also inhibit MAO to some extent, just as the d- enantiomers do. It is somewhat of a wonder that people do not have more problems with selegiline, especially at high doses, that would be reminiscent of parnate, given the effects its metabolites have on the sympathetic nervous system.
> Selegiline is thought to have some dopamine reuptake properties of its own; there's a lot more going on than just MAO-inhibition, even at low doses, though I think the lower the dose, the more the MAO-B-inhibitory effects clearly dominate. Selegiline is an interesting drug with many potential uses that are either indirectly or not related to its role as an MAOI.
> I hadn't heard of it used as a treatment for social phobia, except anecdotally through my doctor, who prescribes it to me at a relatively high dose, where it is thought to behave in that manner like the other non-specific MAOIs. My guess is it probably isn't particularly good for that indication, since it seems to cause agitation and anxiety in some. People take antipsychotics like risperidol sometimes while taking selegiline to reduce some of the side-effects, related to its strong dopaminergic activity. Risperidol as an antidote to selegiline+levodopa-induced psychosis in Parkinson's patients is one thing that comes to mind. I imagine amisulpride would behave similarly.
> It's not suprising that it might have some benefit for people suffering from ADD. The parent compound, without mentioning the metabolites, behaves a bit like an amphetamine.
> I do believe I read somewhere that Kava was, to its indigenous users, a "social lubricant". Since it is a weak MAO-B inibitor, it would seem to follow that selegiline might also be of benefit for social anxiety. It may be, though, that the active compound(s) in Kava behave in other, very different ways than selegiline. I think if one could isolate the effects of enhanced beta-phenylethylamine from some of the more anxiogenic properties of selegiline, this might be a partial explanation. PEA, after all, is the "love chemical", and being in love certainly makes one more ebullient, even in a crowd.
> >
> >
> > Thank you Rick for your informative post. I always enjoy reading your posts and have printed out copies of them before.
> >
> > I didn't make this clear at all in my previous post, but even though I feel my social anxiety is as under control as it has ever been now, I can't say that selegiline (at 5mg/day) has given me any benefit at all. I'm just giving it a trial and watching and hoping for the best.
> >
> > The one study that looked at low dose selegiline and social phobia saw a 33% response rate. This is a modest response, but the result was described to have significance above placebo, if I remember right.
> >
> > It was interesting that selegiline increased your anxiety Rick. Taking amineptine, a dopamine reuptake inhibitor, increased my anxiety or tension. Amineptine is well known for this.
> >
> > My impression is that while evidence shows social anxiety to have a dopaminergic component, it may be more to the point to say that it has a D2 (and possibly D3) receptor component. A recent study indicated that social phobics had lower D2 receptor binding potentials.
> >
> > The antipsychotics amisulpride and sulpiride specifically target the dopamine D2 and D3 receptors. Amisulpride and sulpiride are prescribed overseas sometimes for social anxiety. Evidence shows both of these drugs to be anxiolytic though no studies specific to social anxiety have been done.
> >
> > All in all, social anxiety seems to be poorly understood; biochemical abnormalities in the GABA, serotonergic, andrenergic and dopaminergic neurotransmitter systems have been suggested.
> >
> > I don’t feel I have totally gotten at my social anxiety with my combo of amisulpride and reboxetine. Perhaps some of us need to target more than one neurotransmitter system. I intend to try other anxiolytics in the future such as low dose Klonopin.
> >
> > One more note on selegiline. One study indicated that low dose selegiline was effective for ADD. This study showed a response rate of 60%, comparable to that of stimulants. A poster on another board claimed it improved his ADD symptoms when used with Adderall.
> >
> > Scott, does selegiline metabolize into amphetamine at low doses?
> >
> > AndrewB

Just happened to have read an abstract of an article
that presents evidence that even d-amphetamine appears to
have its major activity on post-synaptic receptors




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