Posted by Scott L. Schofield on January 14, 2000, at 17:36:18
In reply to MAO's which don't have dietary restrictions, posted by Dennis on January 14, 2000, at 11:39:57
> I'm interested in trying an MAO inhibitor, however, I've heard that there are numerous dietary restrictions because of the possibility of these class of drugs interacting with tyramine (enzyme) and causing a dangerous elevation in blood pressure. Are there any MAO's approved by the FDA that do not pose dietary restrictions?
> I've heard that moclobemide does not have this characteristic, although it is my understanding that it's not approved by the FDA. I also read a little bit about similar types of drugs (MAO's) which are commonly used to treat Parkinsons disease to also treat depression (atypical type or people that are non-responsive to other drugs).
Eldepryl (selegiline, l-deprenyl) is often used for Parkinson's Disease, although it was originally developed as an antidepressant. There are two types of MAO enzymes, type A and type B. At low dosages, Eldepryl prefers to inhibit the MAO-B enzyme. Inhibiting MAO-B tends to raise the levels of dopamine (DA), but not serotonin (5-HT) or norepinephrine (NE). Inhibiting the MAO-B enzyme alone does not seem to require dietary restrictions. However, at dosages greater than 30 mg/day, Eldepryl begins to inhibit MAO-A to a degree that warrants these restrictions. From the posts that I've read here, it seems that 40 mg/day or more are needed to it exert an antidepressant effect.
As far as moclobemide (Manerix)is concerned, there are ways to get it from countries like Canada or Mexico that are legal. Usually, these foreign pharmacies will tell you what they require to ship it to you.
I would not consider treatment with moclobemide to be entirely free of dietary considerations. There have been reports of the "cheese-reaction" (hypertensive crisis) occurring with its use.
Using Medline, I found an abstract of an investigation performed by the manufacturer of moclobemide. They studied the effects of tyramine given to healthy subjects while taking it. They looked at different amounts of tyramine given at different dosages of moclobemide. The tyramine challenge certainly caused significant increases in blood-pressure, although I am not sure how the amounts given are representative of actual foods.
Another abstract I found regarding MAOIs reviewed some of the adverse reactions when combined with other drugs and the interactions with foods containing tyramine. With respect of moclobemide, they advised "a degree of caution with regard to the dietary intake of foodstuffs likely to contain a high tyramine content."
I remember reading somewhere that while taking moclobemide, the risk of hypertensive reaction to tyramine can be reduced by not taking it at meal time and not before at least two hours afterwards.
- Scott============================================================
Psychopharmacology (Berl) 1998 Nov;140(2):164-72Clinical pharmacology of moclobemide during chronic administration of high doses to healthy subjects.
Dingemanse J, Wood N, Guentert T, Oie S, Ouwerkerk M, Amrein R
Department of Clinical Pharmacology, F. Hoffmann-La Roche, Basel, Switzerland.The objectives of this study were to assess the tolerability, safety, pharmacodynamics and pharmacokinetics of high-dose moclobemide in healthy subjects. Two sequential groups of six male and six female subjects (eight on active treatment, four on placebo) received for 8 days moclobemide 450 mg b.i.d. and 600 mg b.i.d., respectively. Intravenous tyramine pressor tests were conducted at baseline, at the beginning of treatment and at steady state. Oral tyramine pressor tests with 50, 100 and 150 mg tyramine were conducted under steady-state conditions. Pharmacokinetic parameters of moclobemide and two of its metabolites in plasma and urine were determined after the first and last dose of moclobemide. The incidence and intensity of adverse events was dose-dependent. The most frequently reported adverse events were insomnia, headache, dizziness and dry mouth. The i.v. tyramine pressor sensitivity during both moclobemide dosing regimens was enhanced 3 to 4-fold. Intake of tyramine 50 mg did not result in systolic blood pressure increases greater than 30 mmHg. With regard to blood pressure increases, tyramine 100 mg is still compatible with moclobemide 450 mg b.i.d. but not with 600 mg b.i.d. The clearance of moclobemide decreased by about 60% on multiple dosing, but no differences were found between both dosing regimens. The urinary excretion of the N-oxide metabolite doubled during multiple dosing. In conclusion, the maximum tolerated dose of moclobemide in healthy subjects is 600 mg b.i.d. provided the tyramine content in a meal is not higher than 50 mg.
============================================================
Drug Saf 1996 Apr;14(4):219-27
Monoamine oxidase inhibitors. An update on drug interactions.
Livingston MG, Livingston HM
Department of Psychological Medicine, University of Glasgow, Scotland.After initial enthusiasm, the use of monoamine oxidase inhibitors (MAOIs) has been limited by the wide range of MAOI-drug and MAOI-food interactions that are possible, particularly with sympathomimetic medications or tyramine-containing foods, resulting in hypertensive reactions. Despite their clinical benefits, this has led to a reduction in use of such medications. Discovery of the 2 main subgroups of monoamine oxidase, types A and B, led to the synthesis of MAOIs selective for one or other of these isoenzymes. Consequently, selegiline (deprenyl), a selective MAO-B inhibitor, was developed for the treatment of idiopathic Parkinson's disease. This drug is useful in the treatment of the early stages of the disease and later on as an adjunct to other drug therapies. Although the selective MAO-A inhibitor, clorgiline (clorgyline), was found to be effective in the treatment of depression, it still retained the potential to cause hypertensive reactions. Recently, agents that are not only selective, but reversible in their inhibition of MAO-A (RIMAs) have been synthesised (e.g. moclobemide and toloxatone), and have proven antidepressant efficacy. Whilst they are less likely to induce hypertensive reactions with the concomitant administration of sympathomimetic drugs or with tyramine-rich foodstuffs, it still seems wise to advocate care in co-prescribing potentially interacting medications and to advise a degree of caution with regard to the dietary intake of foodstuffs likely to contain a high tyramine content. Although these newer drugs represent an advance in safety, their use has, as yet, only been established in the treatment of depression. RIMAs also retain a potential for adverse interaction with other drugs. Concomitant prescription of serotonin-enhancing drugs should only be undertaken with caution for patients on moclobemide, toloxatone or selegiline. Coprescription of sympathomimetic drugs should also be avoided with these newer MAOIs and patients should be advised against purchasing over-the-counter preparations that may contain sympathomimetic drugs.
============================================================
poster:Scott L. Schofield
thread:18927
URL: http://www.dr-bob.org/babble/20000112/msgs/18941.html