Posted by SLS on September 9, 2012, at 8:58:48
In reply to Re: Nardil 45 mg to 60 mg (worse?) theory. PST PLZ » gilmourr, posted by phidippus on September 8, 2012, at 16:14:01
> Nardil actually decreases norepinephrine and epinephrine levels through a complicated (I won't bother explaining it) interaction with octopamine,
For anyone who is interested:
MAO inhibitors yield an elevation in the levels of cytosolic octopamine along with norepinephrine (NE). Octopamine becomes a "false transmitter". It competes with NE for vesicular storage. When released along with the NE, it binds to NE receptors, but does not stimulate them. Thus, the increase in NE levels is offset by a simultaneous accumulation of octopamine. Perhaps Phiddipus has data on the net effect that MAOIs have on NE neurotransmission. Is it reduced rather than increased? I wouldn't know where to look for this information. Perhaps it is still increased, but to a lesser degree than serotonin. I just don't know.
> resulting in a lower though still significant therapeutic response, and side effects like orthostatic hypotension.
Clorgyline is the most powerful and selective inhibitor of MAO-A in existence. Clorgyline thus preferentially inhibits the deaminatation (break-down) of serotonin. It is considered by many to be the most effective antidepressant MAOI (although no longer available). It does not increase NE. Therefore, one could make the argument that the accumulation of octopamine has very little influence on the efficacy of Nardil and Parnate.
> If you think you need more norepenephrine, might I suggest Wellbutrin, a strong norepenephrine reuptake inhibitor, or Pristiq, another strong norepenephrine reuptake inhibitor
Interesting choices. I might not be current. I thought the NE reuptake inhibition values of Wellbutrin and Pristiq were rather low compared to tricyclics. Perhaps they are lower, but still sufficient? The Ki of Wellbutrin for NET is 1000.0 or greater. Pristiq is approximately 500.0. By comparison, that of desipramine is 5.0 or lower. (The lower the number, the more potent). Wellbutrin is still a bit of an enigma. Despite its observed effects on transporters, there might be more important mechanisms at work in its therapeutic effects in the treatment of depression. The nitrergic system is currently one area if focus. I know that nicotinic pathways are also being looked at. These mechanisms might have the net effect of increasing NE and/or DA activity. For me, amphetamine and methylphenidate were somewhat activating early in treatment and neutral thereafter. By contrast, Wellbutrin made me significantly more depressed. I am leaning in the direction that the weak NET and DAT inhibition are not a sufficient explanation for its antidepressant effect.
- ScottSome see things as they are and ask why.
I dream of things that never were and ask why not.- George Bernard Shaw
poster:SLS
thread:1025112
URL: http://www.dr-bob.org/babble/20120830/msgs/1025214.html