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Adam: dangling threads from Parnate

Posted by Zeke on December 15, 1999, at 20:53:30

In reply to Re: Parnate: weight gain, & the literature - Adam, posted by Adam on December 15, 1999, at 11:45:04

> > (And you're taking deprenyl right?!!!)
> Yes. Um, I'm not sure what this statement means. Perhaps you are referring to this: taking deprenyl means exposure to l-methamphetamine (some similarities to MDMA) and l-amphetamine. To be honest, I find it rather difficult to understand why people, especially on high oral doses of selegiline, don't have more problems than they do. Serotonin syndrome and spontaneous hypertension seem like obvious potential problems, and yet nobody gets these things with high-dose selegiline monotherapy. I read about selegiline, and it seems like the magic molecule. It protects against oxidative stress by upregulating expression of things like superoxide dismutase. It has antipressor properties that not only protect against its own sympathomimetic metabolites, but even other pressor stimuli like tyramine (IF you take it in small doses). People say it enhances memory and sex drive. What doesn't deprenyl do?

You were referring to MDMA increasing dopamine & dopamine metabolism and in turn which free radicals toxic to the dopamine neurons. And it came to mind that you are taking deprenyl, which of course is an antioxiant specific to dopamine! (Coincidence perhaps but also suggests in part your knowledge in this area.)

I'm glad you responded and said what you did. In sannning MedLine this morning about the 5HT axon damage issue, I learned that this occurs in part because 5HT uptake pumps occur not just at terminals, but all along the axon as well. I guess some reading this will say so what, but I think you will appreciate how this contrasts with what we were taught. It's like recent findings about neurogenesis, about electrical transmission without chemical transmitters, and about the greater importance of the cerebellum. (Actually Robert Heath alluded to this but he has been discounted because of his 'mad science' -- putting active electrodes in human subjects.)

> > Yet I think you'd agree that the significant toxicity is to 5HT processes, and this seems to occur when MDMA is carried inside the neuron, and thus the protective effect of an SSRI. I susbect that MDMA competes with 5HT for entry so initially there is very little MDMA uptake and damage.
> >
> > As for free radical damage, there are MAOis but also other central antioxidants.
> >
> I am frankly a bit confused by the things I read about MDMA and how it causes neuron damage. Excitotoxicity? Oxidative stress? Neither, both, other things?
> I've seen references to use of deprenyl and SSRIs in protecting against MDMA-induced neurotoxicity. In the clinical setting, use of deprenyl at any dose within the time frame needed to give this supposed protective effect would be a tough sell indeed. Not to say you're wrong. I honestly don't know.

The thing that jumped out at me, is that both +MDMA and -MDMA are entactogens, but -MDMA lacks the delayed damage of +MDMA, and the immediate damage is what can be blocked (to whatever degree) by SSRIs and deprenyl.

The one thing that I don't see mentioned re MDMA is an effect on endogenous opioids (ie, enkephalins) which are intermediate between 5HT and dopamine neurons. And the flood of dopamine you mention is supposedly caused by the massive release of 5HT.

> > I think selective MAO inhibitors will be their resurrection. Side effects and interactions are few(er) and rare, and efficacy in depression is being demonstrated. What do you think?
> I'm sure they are efficacious. I don't think they will replace the old, non-selective MAOIs, though. The doctors I am working with right now seem rather unimpressed with the RIMAs,

is RIMA: Reversible Inhibitors of MonoAmine oxidase? or what???

> and that appears to be the consensus, in this country at least.

I'm glad you said "in this country at least" as European researchers seem to be way out in front on the possibilities (eg, derivatives of deprenyl with even more specific properties and applications.)

> What excites me is the transdermal delivery system. It gives the benefits of an MAOI with fewer side effects and no dietary restrictions. I'm not certain why this approach isn't being explored with other MAOIs besides selegiline. I think the head of the study I am participating in mentioned something about Parnate, at least, being a little "too toxic" for this, but I'm not sure what that means (skin irritation?) Maybe its just money, since the patents ran out on the big three a long time ago. But other MAOIs could conceivably be developed, maybe some that are more tolerable in general than the older ones, for transdermal delivery too. This is way, way cool if you ask me.

You know, my mother died of Alzheimer's last year. I unsucessfully tried to get the doctors to try deprenyl -- the last one seemed fearful of psychotic reactions. (They seemed to like the idea of neurolepticss widespite the toxicity of those drugs. BTW she had much less than typical agitation and positive symptoms.) Anyway, you mention transdermals and I think that one other possibility we considered was the nicotine patches used for smoking cessation.




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