Posted by ed_uk on December 27, 2005, at 12:11:34
In reply to Re: What to do if Nardil and Parnate were discontinued » ed_uk, posted by Tomatheus on December 26, 2005, at 23:03:27
Hi Tom
>But let me make it clear that for some Nardil responders, none of options the that you listed below will be adequate substitutes.
I agree. I was just making a few suggestions.
>Unfortunately, the only commercially available MAO-inhibiting mediction in the world is moclobemide
I think pirlindole is still available in Russia (as Pyrazidol) and Portugal (as Implementor). Pirlindole seems to have been studied mainly in Russia.
>it is not uncommon or unreasonable to hypothesize that moclobemide is less effective than MAOIs such as Nardil and Parnate because moclobemide only inhibits MAO-A without inhibiting MAO-B
I think it's highly likely. See.......
The author examined the acute anxiolytic effects of monoamine oxidase inhibitors on freezing behavior, a putative index of anxiety, induced by conditioned fear stress. The selective serotonin1A receptor agonist inhibited freezing dose dependently. The irreversible, non-selective monoamine oxidase inhibitors tranylcypromine (3 and 15 mg/kg) and phenelzine (30 and 80 mg/kg) reduced freezing significantly. Clorgyline (10 mg/kg, irreversible selective monoamine oxidase A inhibitor), Ro 41-1049 (30 mg/kg, reversible selective monoamine oxidase A inhibitor), selegiline (3 mg/kg, irreversible selective monoamine oxidase B inhibitor) and lazabemide (10 mg/kg, reversible selective monoamine oxidase B inhibitor) had no effect on freezing behavior. However, combined administration of clorgyline (10 mg/kg) and selegiline (3 mg/kg) reduced freezing significantly, as well as combined administration of clorgyline (10 mg/kg) and lazabemide (10 mg/kg), Ro 41-1049 (30 mg/kg) and selegiline (3 mg/kg), or Ro 41-1049 (30 mg/kg) and lazabemide (10 mg/kg). These effects of monoamine oxidase inhibitors on freezing were not due to non-specific motor effects.
These results suggest that acute inhibition of both monoamine oxidase A and B reduces anxiety or fear, while inhibition of monoamine oxidase A or B alone fails to reduce anxiety or fear. In vivo microdialysis studies showed that the irreversible monoamine oxidase A inhibitor clorgyline and the irreversible monoamine oxidase B inhibitor selegiline induced a mild increase and no increase in extracellular serotonin, respectively. Interestingly, the combined treatment with clorgyline and selegiline resulted in much larger increases in extracellular serotonin in the medial prefrontal cortex than did either monoamine oxidase inhibitor alone. Our previous studies have indicated that facilitation of 5-HT neurotransmission decreases conditioned freezing, i.e., anxiety or fear. The results of these in vivo microdialysis studies may account for the results of this study that the simultaneous blockade of both monoamine oxidase A and B reduced conditioned freezing, whereas blockade of either monoamine oxidase alone failed.
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It is my belief that the co-administration of moclobemide with a low dose of rasagiline (eg. 1mg/day) might produce a substantial anxiolytic/antidepressant effect in some patients. As is the case with traditional MAOIs, a low tyramine diet would be necessary.
>is typically described in the scientific literature as being a highly effective antidepressant
The scientific literature has a tendency to describe most drugs as 'potent' ;-)
>moclobemide does not produce the "true" benefits of MAO-A inhibition
Perhaps. It's short elimination half life may be relevant. It might work better in multiple divided doses eg. 300mg three times a day.
>So, the point that I'm trying to make by citing all these facts is that moclobemide's lackluster efficacy is probably not due to the fact that it inhibits MAO-A without also inhibiting MAO-B; it likely has more to do with the strong possibility that moclobemide does not produce the "true" benefits of MAO-A inhibition.
Potent inhibition of MAO-A alone seems to produce only small rises in extracellular serotonin. The anxiolytic efficacy of clorgyline is likely to be weak. Inhibition of both forms of MAO may be necessary to produce a substantial effect. The anxiolytic/antidepressant efficacy of phenelzine (Nardil) is likely to be closely linked to its strong serotonergic properties. Of course, Nardil has other pharmacological actions which may also play a role. Moclobemide alone appears to be (only) weakly serotonergic.
>it's highly unlikely that they would benefit significantly from medications such as selegiline and rasagiline
Perhaps not alone, but in combination with moclobemide such medications may be useful.
> But if anybody gets the idea from reading your post that a vast majority of Nardil responders will be able to find effective alternatives, then they better think again.
Ouch, that hurt.
Regards
Ed
poster:ed_uk
thread:591969
URL: http://www.dr-bob.org/babble/20051221/msgs/592416.html