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Re: reboxetine and...?

Posted by Adam on August 9, 1999, at 23:24:27

In reply to Re: reboxetine and...?, posted by Adam on August 9, 1999, at 17:18:39

Actually, the more I read this abstract, the more it bugs me. The authors describe experiments in which they inject tyramine
intravenously into rats with and without tranylcypromine pretreatment. Given this model, I'm not sure what the point of
tranylcypromine pretreatment is. The problem with parnate and tyramine is that it prevents tyramine from being broken down
in the gut, allowing it to get into the blood. If you go and inject it directly into the blood, that's pretty much the same
thing, isn't it? Also, if tyramine can bind NE receptors, perhaps it also binds the receptors that are involved in NE reuptake.
If that were the case, it would be internalized in the cell, and hence you would detect the radiolabel in the tissue. If there
is a NE reuptake blocker like reboxetine around, then it stands to reason it would also prevent the uptake of tyramine into
the cell, leaving it in the extracellular environment, where it might be flushed away and not detected during harvesting of the
heart tissue.

This could conceivably make things worse, not better. If more tyramine were in the extracellular environment, rather than
being internalized, it would just be more available for binding to cell-surface NE receptors.

Oh well. I was kind of excited by this the first time I read it. But after posting here, I got thinking about it, and now
I'm not so sure. Sorry, folks.

> I, of course, have no medical expertise to comment on the claims made by the authors of this paper, nor do I know much about
> the quality of Italian research in psychopharmacology, but the abstract would suggest that not only is it safe to take reboxetine
> and tranylcypromine (Parnate) at the same time, reboxetine may abrogate the cheese effect.
> Again, I have no idea if one should take this notion seriously. From what I understand, though, part of the problem with tyramine
> is that it is a norepinepherine mimetic, and binds to receptors on cells that are involved in regulation of blood pressure, sending
> the wrong kinds of signals, somehow. I suppose that if there were something around that could boost the levels of NE, maybe there
> would be enough around to out-compete tyramine binding. This is pure speculation on my part.
> Couldn't hurt to run this by your doctors, though. I have heard that they are still trying to get reboxetine approved for marketing
> in the USA, and that it could be available in less than a year.
> Reboxetine prevents the tranylcypromine-induced
> increase in tyramine levels in rat heart.
> by
> Dostert P, Castelli MG, Cicioni P, Strolin Benedetti M
> Farmitalia Carlo Erba, Research and Development, Erbamont Group, Milan, Italy.
> J Neural Transm Suppl 1994; 41:149-53
> This study aimed to examine whether the increase in heart radioactivity levels after intravenous injection of
> 14C-tyramine to rats pretreated with the irreversible MAO inhibitor tranylcypromine could be antagonized by
> reboxetine, a potent and selective noradrenaline uptake blocker. Reboxetine was found totally to abolish the effect
> of tranylcypromine. Heart radioactivity levels after reboxetine and tranylcypromine were very similar to those found
> when tyramine was injected after reboxetine only. These results suggest that reboxetine might be advantageously
> combined with tranylcypromine, or any MAO inhibitor, in depressed patients unresponsive of either treatment given
> alone.
> > > Does anyone know if it's possible to comine these drugs? If there would be a reason to do so?
> >
> > Someone who lives in the UK or another country where reboxetine is used can probably answer this better than I can, but I think the answers are yes and yes.
> >
> > My question is, what about reboxetine and MAOIs? Have there been any interactions reported there? Is there any reason to think there would be?




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