Posted by ikasug on March 11, 2015, at 12:38:20
In reply to MAOIs, hypotension, mental and muscular weakness, posted by Robert_Burton_1621 on March 10, 2015, at 21:45:19
> This is my fifth week on parnate. I had, in the initial stages, thought I would be lucky enough to escape the hypotension and weakness side-effects, but alas, no!
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> I do *not* appear to have postural hypotension (as evidenced by a 20mmhg drop within 3 minutes), but my BP has definitely lowered (on occassion, systolic has been lower than 90mmhg).
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> I am having significant trouble with the side-effects which I assume are flowing from this: light-headedness and dizziness, weakness, fatigue, lack of motivation, nausea, gastrointestinal, etc.
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> I do not wish to stop parnate because in other respects it has been good, and it is still only a month since I started.
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> I was wondering what others did or do to counter these side-effects? I understand that, in time, it is possible for the body to become accustomed to the drop in BP. I also have heard that experimenting with dosage times may help, on the ground that weakness may coincide with peak plasma levels of the drug.
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> But there is another theory I have just come across which attempts to explain the hypotension by reference to the MAOI-induced replacement of noradrenaline by octopamine, the later as a "false neurochemical transmitter" which has distinctly weaker adrenergic properties than noradrenaline. This is hypothesised to result in reduced sympathetic responsiveness.
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> The theory was adverted to in a 2010 post at this site: http://www.dr-bob.org/babble/20100604/msgs/950791.html
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> It was also suggested that adding an NRI to an MAOI may work to reverse the putative decrease in noradrenaline.
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> I am going to ask my specialist tomorrow about all this. If anyone has any ideas, I would be grateful to hear them.
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> The original post here cited wikipedia only. So I've done a bit more research and post the results below. The research is quite old, but I've no idea whether that means it has been positively disproved or otherwise superseded.
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> Thanks a lot.
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> oSee D.P. Holschneider, M.D. and J.C. Shih, Ph.D, Monoamine Oxidase: Basic and Clinical Perspectives in Psychopharmacology: the Fourth Generation of Progress (2000). 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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> oSee also Horita, Annual Reports in Medical Chemistry 1965, Chapt 25, pp 280 82: The mechanism of the blood pressure lowering effect of the MAO inhibitors has been attributed to various causes, but the most attractive hypothesis based on MAO inhibition is that of Kopin and associates. These authors postulate that after MAO inhibition an accumulation of octopamine occurs at adrenergic nerve terminals because of the loss of the normal deanimation pathway. The octopamine is thought to replace part of the normal stores of sympathetic mediator, and upon stimulation, it is released as a false transmitter. Octopamine, however, is at best a poor substitute for norepinephrine, and this results in a diminished sympathetic response and hypotension. . . . The false transmitter concept has received support from Farmer (p 280). Internal references: Kopin I.J. (et al), Evidence for a False Neurochemical Transmitter as a Mechanism for the Hypotensive Effect of Monoamine Oxidase Inhibitors, Proc Natl Acad Sci USA (1964) 52(7), pp 716-21; Kopin I.J., False Neurochemical Transmitters and the Mechanism of Sympathetic Blockade by MAOIs, J Pharmacol Exp Ther (1965) 147, 186-93.
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> oSee also, op cit, at p 15, per Biel: The False Neurochemical Transmitter theory promulgated by Kopin . . . to explain the sympathetic blocking of properties of the MAO inhibitors, must be seriously considered also with respect to the central properties of these agents. In essence, this hypothesis proposes that MAO inhibition will produce an accumulation of sypathomimetic metabolites which are normally not present in the body, but have a sufficient affinity for the adrenergic receptor sites to displace the regularly present neurotransmitters (e.g., norepinephrine, dopamine) from sympathetic nerve endings. Furthermore, the sympathetic nerve stimulation will release these agents in the same manner as it does NE; however, the resultant effect will be greatly diluted, since the false neurotransmitters have distinctly weaker adrenergic properties than NE or dopamine. Normally, tyramine is rapidly metabolised by MAO so that little, in any, octopamine is formed. In the presence of the MAO inhibitors. however, significant amounts of octopamine are produced.
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> oSee also, Mechanisms of Release of Biogenic Amines (1966): Replacement of a neurotransmitter at its storage site by a closely related molecule which can function as a relatively ineffective false transmitter has been considered for both cholinergic and adrenergic nerve endings. . . . Replacement of norepinephrine by a false transmitter has been implicated in the diminished sympathetic responsiveness seen after treatment with . . . MAOIs (Kopin, Fisher, Musacchio and Horst, 1964). (pp 232 233).
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> oSee also, Phillis, J.W., The Pharmacology of Synapses (1974): Although noradrenaline is normally the only adrenergic transmitter in mammals, it is not clear that sever other structurally related amines can be released from sympathetic never terminals by nerve stimulation. Such compounds, which can be stored in place of noradrenaline in adrenergic nerve terminals and released by nerve stimulation have been called false transmitters. If the false transmitter has reduced physiological activity, there may be a failure of transmission at affected synaptic junctions. . . . In peripheral sympathetically innervated tissues of animals pre-treated with a monoamine oxidase inhibitor, there is an increase in endogenous tyramine and its hydroxylated derivative, octopamine. The latter amine accumulates in nerve endings and is released by nerve stimulation, acting as a false transmitter in competition with noradrenaline. Similarly, after monoamine oxidase inhibition, endogenous octopamine, synthesised by tyramine, accumulate[s] in the brain. The localisation of labelled octopamine in a synaptosomal subcellular fraction suggests that this noradrenaline analogue may act as a false transmitter in the brain. (p 48)
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> oSee also On the Identification of Octopamine in Mammals, J Biol Chem (1962) 237(2): In the past there was a tendency to ascribe clinical effects of the monoamine oxidase inhibitors to an increased level of norepinephrine and serotonin in tissues. More recently, the finding that dopamine, p-tyramine, and tryptamine are normal metabolites has made it necessary to consider the possible physiological effects of increased levels of these and perhaps other amines. The present work makes it apparent that octopamine should receive special attention in connection with physiological effects of monoamine oxidase inhibitors because of its rapid destruction in vivo and the fact that the proportionate increase in tissue levels after monoamine oxidase blockade is far greater than that of any other of the amines. (p 426)
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>I've been on Parnate for a few years now, and it took me a while to overcome the very low blood pressure you're describing. I had postural hypotension as well, and I had come to believe they were connected because MAOI medications do lower general blood pressure.
After a while my BP rose to about 100-110/60. Nonetheless, if I am not compliant or titrate upwards, the blood pressure symptoms return for a few days.
I found relief by dividing the dose into groups of 30mg.
poster:ikasug
thread:1077436
URL: http://www.dr-bob.org/babble/20150223/msgs/1077453.html