Posted by Elizabeth on November 30, 2001, at 2:21:54
In reply to Why Is Nardil superior to SSRIs for SP, posted by PaulB on November 29, 2001, at 22:32:57
I think you might have a mistaken idea of what "selective" in "selective serotonin reuptake inhibitor" means. There's only one "type of serotonin." SSRIs increase the amount of serotonin available outside of neurons; serotonin is an agonist at all types of serotonin *receptors* (there were 14 known serotonin receptor subtypes, last I checked).
SSRIs are "selective" in that they don't inhibit the reuptake of other monoamines (much) at prescribed doses. (Dopamine is an example of another monoamine besides serotonin.) They also selectively block the serotonin transporter (the reuptake site) without much (direct) effect on other receptor types (for example, they don't block type 2c serotonin receptors, they don't activate histamine receptors, etc.).
Monoamine oxidase inhibitors, in contrast, increase the amount of monoamines available -- in the brain and elsewhere. (MAO is found all over the body, really; it's kind of amazing how few side effects they have, considering how widespread their effect is.) This means all monoamines, not just serotonin.
The available MAOIs also have other effects. Phenelzine, for example, increases the amount of the inhibitory neurotransmitter GABA (gamma-aminobutyric acid) in the brain. (To give you an idea of what GABA might have to do with anxiety, consider that benzodiazepines such as Valium, Ativan, Xanax, etc., work by increasing the effectiveness of GABA.) Parnate is thought to have some amphetamine-like (stimulant) effects, although nobody ever bothered to find out what these effects might be (it's an old drug, off patent, and there's little interest in studying it, although there is a lot we could learn).
None of this really explains why Nardil or Parnate might be better for social phobia than the SSRIs; practically, it just seems that they are. (This is because nobody really knows the cause of social phobia (or any other psych disorder) on a biomolecular level.) Nardil has been more extensively tested, and because of its effect on GABA concentrations there's reason to believe it might be more effective, than Parnate for anxiety disorders (although Parnate is known to work for SP also, they've never been tested against each other).
Moclobemide, incidentally, probably isn't any better than the SSRIs for social phobia (or, for that matter, depression). Moclobemide is a reversible (competitive) MAOI, meaning that it displaces other substrates, but doesn't effectively destroy the enzyme the way that Nardil, Parnate, Marplan, Marsilid, etc. do.
-elizabeth
poster:Elizabeth
thread:85575
URL: http://www.dr-bob.org/babble/20011123/msgs/85601.html