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Re: Mode of action unknown Bob

Posted by Chairman_MAO on May 8, 2005, at 12:28:18

In reply to Re: Mode of action unknown Chairman_MAO, posted by Bob on May 7, 2005, at 13:48:24

The new theories concerning many types of DEPRESSION involve neurosteroids, second messenger systems/G-protein coupled receptors, etc. Of course fiddling with the monoamines can produce many effects, and of course they're intimately involved in mood, cognition, etc, but the theories that appeal to simple "chemical imbalances" and "neurotransmitter deficiencies" are utterly out of date.

Anxiety is a different story, although that also is mediated not just monoaminergically, but GABAnergically, by CCK, neurosteroids (allopregnanolone), etc. What I believe is that consciousness is the sum total of all neural activity (a la Daniel Dennett's "multiple drafts model"), and so to isolate any one neurotransmitter system/subsystem and say that it is responsible for something as complex as depression is absurd.

I believe MAOIs work better for many people because they act in a fundamentally different way than reuptake inhibitors, etc. That is, they alter the catabolism of neurotransmitters, and it is that simple alteration that produces a cascade of events while the brain attempts to restore homeostasis. It is the newfound homeostasis built around the elevated levels of monoamines (and GABA, with phenelzine) that produces the antidepressant/anxiolytic effect. You may say, "Hey, but reuptake inhibitors are doing the same thing, just by a different mechanism" Well, that is partially correct, however MAO is present INSIDE neurons themselves, and so--if I am correct here--taking an MAOI can actually alter the amount of neurotransmitter stored INSIDE a given neuron. Anyone that's taken a drug (such as cocaine) or a combination of drugs that blocks the reuptake of all three monoamines and also has taken an MAOI knows that the qualitative effect of the drugs are vastly different. There are many reasons for this, most, I believe, we are not capable of elucidating given the current state of the science. I know when I took Effexor + amphetamine and Effexor + Ritalin, or lexapro + selegiline, the effects were absolutely nothing like Nardil or Parnate in any way.


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