Posted by King Vultan on April 25, 2004, at 10:03:37
In reply to Re: MAOI causes hypotension - What's the mechanism?, posted by SLS on April 24, 2004, at 21:14:35
> OK. It looks like we were both wrong - at least according to what little I could find on the Net. I wish I could have found something more definitive, though. Maybe you'll have better luck.
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> I get the impression that the mechanisms by which MAOIs produce hypotension are poorly understood. One piece that I found stated that it definitely was not due to NE alpha-1 antagonism. The following is an excerpt from:
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> http://www.acnp.org/g4/GN401000046/CH046.html
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> SIDE EFFECTS OF MAOIS
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> Orthostatic Hypotension
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> Orthostatic hypotension is a common side effect of the irreversible MAOIs, particularly phenelzine (Table 4). Clinically, the development of orthostatic symptoms is gradual and appears generally after 2–3 weeks of treatment. The relationship of the time course of this response to the etiology of orthostasis remains unclear. Some have suggested it may represent a compensatory down-regulation of peripheral ganglionic effects in response to central sympathetic stimulation. Others have proposed that inhibition of amine metabolism results in an artificial, supraphysiologic elevation of amines with few or no pressor effects and the resultant replacement of amines with greater pressor effects from intracellular amine stores. Gradual accumulation of octopamine in adrenergic neurons, for instance, may be the result of MAO inhibition and resultant alternate hydroxylation of tyramine to octopamine. It has been suggested that octopamine may replace NE from intra-axonal storage granules. Octopamine released upon sympathetic stimulation may act as a 'false neurotransmitter' with minimal activity at a- or b-adrenergic receptors. The result is a functional block of sympathetic neurotransmission, accompanied by decreased ability to regulate blood pressure in response to postural changes.
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> - Scott
Wow, is that complicated--I think I'd have to do quite a bit of research in order to come to some type of opinion as to what is actually going on. I think we also need to take into account the common reduction in heart rate also, which one would think is related somehow. My BP has gone down about 30/20, and my pulse has decreased about 20 bpm since going on Nardil.I've been on the tricyclics also, which also made my BP go down but caused my heart rate to increase. Here, it seems clear that the decrease in BP is due to alpha-1 antagonism. Preskorn (www.preskorn.com) says that desipramine does not blockade the alpha-1 adrenergic receptor, but my BP definitely went down as I increased the dosage, and then went up as I came off the med. I also take an alpha-1 blocker for a minor prostate condition and found I had to increase the dosage as I came off the desipramine.
The increase in heart rate I noticed on tricyclics appears to be due to blockade of norepinephrine reuptake and subsequent stimulation of beta adrenergic receptors. There is a concurrent tendency to increase blood pressure from this effect also, but at least in my case, the alpha-1 antagonism won out, and I had a net decrease in BP, at least at higher dosages. Some people do experience an increase in BP on tricyclics, but I think this is more common on drugs that block NE reuptake but do not have an alpha-1 blockade, such as Effexor.
Todd
poster:King Vultan
thread:339531
URL: http://www.dr-bob.org/babble/20040423/msgs/339828.html