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Re: Provigil-Modafinil-Adrafinil? Rick

Posted by on January 6, 2002, at 9:52:10

In reply to Re: Provigil-Modafinil-Adrafinil? christophrejmc, posted by Rick on January 5, 2002, at 15:03:13

Rick -

I had a hard time not acknowledging the "SP and dopamine" issue:
I definitely do *not* think dopamine agonists are required for all people with SP.
I'm also not too clear if dopaminergics work equally well for women as men.
I *do* think a majority of males with moderate to severe SP AND timidity AND high rejection sensitivity will attain their best results with dopamine augmentation.

Although I could cite solid suggesting evidence (best) or my own regimen and experience, instead I suggest your regimen acts as a dopamine and GABA agonist with less effect on SE and NE.

100 Provigil (5ht, DA): (effect perhaps partially indirect via GABA) Site specific but clearly has characteristics of DA agonist and ex vivo shows DA re-uptake. Higher doses lead to increased wakefullness, stimulant and (at first) euphoric properties. Is self-reinforcing. Increased libido, hair loss, effective antagonist of the atypical antipsychotic clozaril.

300 Serzone: Often "prosexual" (suggestive dopamine agonist or at worst lacks net DA decline, probably indirectly by primary action as 5ht-2 antagonist.) Common side effects: increased sex drive, agitation, irritablity, hypotension. Up to date info (Medline) indicates that Serzone has *weak* 5ht re-uptake and it's *primary* effect is as 5ht-2 antagonist.

1.25 Klonopin: May cause Increase libido (in PDR also), paradoxic reaction at high dose such as aggressive behavior, hyperactivity, increased locomotion, agitation, impulsiveness, increased self-confidence, reduced rejection sensitivity. Klonopin is a 2nd line MOOD STABILIZER for bipolar swings. This suggests Klonopin compensate for low dopamine levels. Also, Davidson (1992) suggest Klonopin may have dopaminergic agonism, possibly by the overall anti-serotonin properties of Klonopin (unlike Xanax for example, which is sometimes used as anti-depressant).

Sum: Provigil: DA++ (dose dependent)
Serzone: DA or DA+
Klonopin: DA, DA+, unlikely DA-

Provigil's ability to effectively antagonize clozaril,
and ability to offset amisulpride induced energy/motor deficits
both additional evidence for DA agonism.

"Dopaminergics and anxiety": Many DA agonists also boost NE, and NE is typically more responsibe for anxiety reactions.

Examples: Eldepryl: DA++, NE++ (predict anxiety)
Wellbutrin: DA++, NE++ (predict anxiety)
Ritalin: DA++, NE++ (predict anxiety)
aminetpine: DA++, NE++ (predict anxiety)
Provigil: SE+,DA+ (predict stimulating mood lift)
Dexedrine: SE++,DA++,NE++ (predict activating feel good, confidence, energy)

amantadine: DA++, NE+ (high energy, boost sex, mild anxiety)


> No, never been on amphetamines. The selegiline metabolites are the closest I've come.
> But the key here is that the amphetamine metabolites are likely *not* the cause of the anxiety selegiline produced. Instead -- despite the talk of dopamine deficiency in social phobia -- I find that dopaminergic agents in general make me a lot more anxious. And I'm not the only one...most attempts to harness dopamine for social phobia have been major failures, such as the selegiline study I mentioned as well as a pergolide study where the results were so negative that the study was quickly aborted.
> That doesn't mean dopamine enhancement can't play a role in social phobia treatment in some as-yet undetermined fashion. But dopamine's a complex and rather mysterious substance that can have diametrically opposing mental and physical (e.g., blood pressure modulating) impact at different binding sites, etc.
> Rick
> > > Even a tiny dose that I later used to (successfully) offset slight Klonopin-induced dulling added back some anxiety.
> > Have you ever been on an amphetamine (Adderall, Dexedrine, Desoxyn)? If so, did it cause the same anxiety you experienced with selegiline? (As I'm sure you know, two of selegiline's metabolites are l-amphetamine and l-methamphetamine.)
> > I'm considering trying selegiline for my depression & social phobia. (Amphetamines don't really increase my anxiety (in fact, sometimes they relieve it).)
> > Thanks,
> > Christophre




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