Posted by Dave001 on June 20, 2005, at 19:19:12
In reply to Re: Selegiline Pharmacology » St James » Oracle » chemist, posted by Ron Hill on June 18, 2005, at 14:49:04
>> the MAO-A/B switch that you mention is a mystery: the drug is an
>> MAO-B inhibitor as low doses, and a dopamine uptake inhibitor at
>> high doses.
> Do you have any pharmacological research data that support the claim
> that Selegiline is a dopamine uptake inhibitor at high dosages and
> that it is not an MAOI-A? The medical research data repeated state
> that Selegiline is a selective MAOI-B up to a dosage of about 15 - 20
> mg/day at which point it loses its selectivity and becomes an MAOI-A
> and an MAOI-B.
> Therefore, please post the link(s) that support the claim that
> Selegiline is a dopamine uptake inhibitor at high dosages and not an
I'm not the person to whom your post is in response, but I thought I
would add that for the most part, your understanding is in line with the
current medical understanding of selegiline.
It does appear to retain its selectivity for MAO-B at the doses
typically used to treat Parkinson's disease. (Or at least, the level of
MAO-A inhibition does not seem to be clinically significant at those doses.)
I am also not aware that at higher doses a prominent inhibitory effect
of dopamine uptake is present. Then again, that is not an issue that
I've spent a lot of time trying resolve... Perhaps it is true. One paper
I've seen did indicate an inhibitory effect on dopamine uptake from
deprenyl (Fang and Yu, 1994). However, the effect from l-deprenyl was
quite weak on that parameter; by contrast, *d-deprenyl* was quite potent
at inhibiting dopamine uptake. Perhaps "chemist" or whomever it was that
contradicted your understanding, mistakenly confused the optical isomers
of deprenyl. Selegiline is l-deprenyl. That's just speculation though;
you'll have to wait for him to clarify the discrepancy.
Fang, J. and P. H. Yu (1994). "Effect of L-deprenyl, its structural
analogues and some monoamine oxidase inhibitors on dopamine uptake."
Neuropharmacology 33(6): 763-8.