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Re: ENSAM Question

Posted by SLS on January 13, 2007, at 5:10:57

In reply to Re: ENSAM Question, posted by SLS on January 13, 2007, at 5:04:59

> > I understand Deprenyl at low-medium doses is a MAOI-B inhibitor, not affecting serotonin or MAOI-A. But what about Ensam patch, say at 9mg or less. Does Ensam work as a MAOI-B and MAOI-A, or just MAOI-B?
>
> I believe you begin to see MAO-A inhibition at that dosage. I'll check the monograph and see if it says anything about it.

Apparantly, MAO-A inhibition occurs at all dosages:

"CLINICAL PHARMACOLOGY

Pharmacodynamics

Selegiline (the drug substance of EMSAM) is an irreversible inhibitor of monoamine oxidase (MAO), an intracellular enzyme associated with the outer membrane of mitochondria. MAO exists as two isoenzymes, referred to as MAO-A and MAO-B. Selegiline has a greater affinity for MAO-B, compared to MAO-A. However, at antidepressant doses, selegiline inhibits both isoenzymes (see below). The mechanism of action of EMSAM as an antidepressant is not fully understood, but is presumed to be linked to potentiation of monoamine neurotransmitter activity in the central nervous system (CNS) resulting from its inhibition of MAO activity. In an in vivo animal model used to test for antidepressant activity (Forced Swim Test), selegiline administered by transdermal patch exhibited antidepressant properties only at doses that inhibited both MAO-A and MAO-B activity in the brain. In the CNS, MAO-A and MAO-B play important roles in the catabolism of neurotransmitter amines such as norepinephrine, dopamine, and serotonin, as well as neuromodulators such as phenylethylamine. Other molecular sites of action have also been explored and in this regard, a direct pharmacological interaction may also occur between selegiline and brain neuronal a2B receptors. In in vitro receptor binding assays, selegiline has demonstrated affinity for the human recombinant adrenergic a2B receptor (Ki = 284 µM). No affinity [Ki >10 µM] was noted at dopamine receptors, adrenergic ß3, glutamate, muscarinic M1-M5, nicotinic, or rolipram receptor/sites."


- Scott

 

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poster:SLS thread:721900
URL: http://www.dr-bob.org/babble/20070113/msgs/721910.html