Posted by Larry Hoover on December 20, 2008, at 17:14:41
In reply to Selegiline: Metabolites and MAO-B Inhibition, posted by karl on December 19, 2008, at 18:17:06
Hey, karl. I haven't noticed your posts before. If you're new, welcome to babble.
> those who take selegiline or are considering it might try to understand the different feelings they get from the two different actions of the drug, 1) metabolites and 2) mao-b inhibition. if it's the metabolites that are making them feel better, they should know that one can buy the major metabolite of the selegiline molecule, levo-methamphetamine, at the drug store and that they may not need to order selegiline from overseas or pay $600/month for emsam patches. it's called levmetamfetamine now [to try to discourage abuse] and they put it in Vicks Inhalers, although according to wikipedia Vicks soaks a piece of cotton with it and with menthol and camphor, so dosing is obviously tricky if not impossible. i don't know where one could obtain pure levmetamfetamine. if you know, kindly post a follow-up.
I fear you have constructed what is logically a false dilemma; we don't know that selegiline acts solely via these two mechanisms. We know that selegiline has substantial affinity for the alpha-2b adrenoceptor, but that interaction has not been characterized as agonistic or antagonistic. Moreover, similar structures modulate endogenous opioid metabolism, so the mechanisms of action are not clear cut.
In any case, I don't know how anyone could properly attribute the drug's effects to either of the choices you offer. Users would experience a variety of effects, acute and chronic. L-methamphetamine is not generally considered to be psychotropic, at least in doses likely to arise from selegiline at its commonly used doses. You can obtain L-methamphetamine, if you're an accredited researcher. Expect some scrutiny if you try to obtain it.
> if you feel like trying some mao-b inhibition on its own with as little methamphetamine floating around in your system as possible and screwing up your sleep, or already are using selegiline for this purpose and feel it may be helping you, you don't need much selegiline, you don't have to put it under your tongue, and you don't have to take it very often:
>
> "MAO-B is irreversibly inhibited by 90% within 30-90 minutes, and remains so until it can be re-synthesized by the body -- a period of up to 40 days."Fair enough, but that MAO-B effect is not the sole effect, either. Selegiline is psychotropic, so there must surely be some other mechanism at play.
> http://apple2.org.za/gswv/me/selegiline.structure.pdf
>
> "...by 96 hours (four doses) the inhibition of platelet MAO-B activity is approximately 95% after a daily [oral] dose of 2.5 mg selegiline [hydrochloride], whereas it takes only 48 hours (two doses) for doses of 5 mg and 7.5 mg to achieve this degree of inhibition."
>
> [parentheses mine; the words appear in the abstract if you care to click it below]
>
> http://www.ncbi.nlm.nih.gov/pubmed/9853994?ordinalpos=2&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_DefaultReportPanel.Pubmed_RVDocSumPlatelet MAO activity may well be substantially different than that found within the central nervous system, after selegiline exposure. I know it crosses the blood-brain barrier readily, but I'd want to see some evidence of rates of inhibition there.
> and as far as any reasonable science is concerned, it makes no difference to the body whether the selegiline molecule is accompanied by a hydrochloride or a citrate. any website claiming otherwise would do well to provide some scientific explanation and citation for their claim.
Yes, the citrate and hydrochloride are of similar efficacy.
> something else i've seen talked about is co-supplementation of selegiline with DLPA [dextro/levo phenylalanine]. i don't really see the point here, since phenylalanine is just one of the amino acids that make up the proteins that compose a large part of most humans' diets anyway. for example, 1/4 pound of ground chuck has 783mg of phenylalanine. [http://www.nutritiondata.com/facts/beef-products/6205/2]D-phenylalanine has biological effects rather distinct from the L-phenylalanine found in that ground chuck, as an example.
D-phenylalanine cannot bind to the enzyme that converts L-phenylalanine to tyrosine, so it does not encourage dopamine synthesis. Instead, it remains available to be converted to phenylethylamine (PEA), a neuromodulator. As PEA is a substrate of MAO-B, selegiline further enhances any PEA-modulated effects of D-PA ingestion. Moreover, D-PA is an inhibitor of the enzyme enkephalase, which breaks down one of the endogenous opioids, enkephalin. This may be why DLPA has obtained a reputation as an analgesic.
Taking free-form high-dose pure aminos is very different than obtaining them from food. The bolus dose causes substantial increases in blood concentrations of whatever amino it is that you've supplemented, without influencing the concentration of all the others. Receptors, enzymes, transporters all "see" this concentration bolus as changes in activity and/or yield. For example, the transporter that moves phenylalanine across the blood brain barrier (called LNAAT) is employed by six amino acids (and some drugs). By spiking the blood concentration, phenylalanine binding to that transporter is more likely, and brain uptake is similarly enhanced. In effect, you're using the amino acid as a drug. You can't get that effect from food.
Regards,
Lar
poster:Larry Hoover
thread:869704
URL: http://www.dr-bob.org/babble/20081214/msgs/869894.html