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Re: Me thinks this is very interesting indeed (long)

Posted by ed_uk on January 4, 2005, at 12:52:23

In reply to Me thinks this is very interesting indeed (long), posted by Michael Bell on January 3, 2005, at 23:56:23

Hello Michael!

Did you see these.........

Psychopharmacology (Berl). 1992;106 Suppl:S35-6.

Interaction of moclobemide and tricyclic antidepressants with the tyramine pressor effect in rats.

Burkard W, d'Agostini F, Kettler R, Da Prada M.

Pharmaceutical Research Department, F. Hoffmann-La Roche Ltd, Basel, Switzerland.

Tyramine at high doses (20 mg/kg) increased arterial blood pressure in freely moving rats. This increase was completely prevented by pretreatment with inhibitors of neuronal membrane carriers for noradrenaline (e.g. desipramine or oxaprotiline). Pretreatment with moclobemide induced a mild potentiation of this tyramine-pressor effect which could also be attenuated dose-dependently by co-administration of oxaprotiline.

Acta Psychiatr Scand Suppl. 1990;360:106-7. Related Articles, Links

Hypotensive action and weak potentiation of tyramine effect by moclobemide in rats.

Da Prada M, Burkard WP.

Pharmaceutical Research Department, F. Hoffmann-La Roche, Basle, Switzerland.

Moclobemide belongs to a new class of reversible, selective monoamine oxidase-A (MAO-A) inhibitors; it is clinically well tolerated and has little liability to potentiate tyramine pressor effects. Measurement of blood pressure and heart rate in conscious, freely moving rats showed only a slight, nonsignificant decrease in mean arterial pressure in normotensive animals. However, in spontaneously hypertensive rats, moclobemide significantly decreased blood pressure by 20 mmHg within 30 min of oral intake of 30 mg/kg. In the same animals, heart rate was decreased by 20%; normal values returned after 2-3 h. Tyramine alone in oral doses up to 15 mg/kg had no effect on blood pressure in normotensive rats, and after treatment with 30 mg/kg moclobemide, tyramine at 5 mg/kg did not alter mean arterial pressure, whereas there was a significant increase after doses of tranylcypromine, toloxatone and brofaromine. Higher doses of tyramine (10-20 mg/kg) following moclobemide led to a rise of 30-40 mmHg in pressure, but this had disappeared within 20 min. This effect was almost completely eliminated by desipramine, suggesting that coadministration of a norepinephrine uptake inhibitor with a reversible MAO inhibitor is likely to reduce the risk of tyramine-induced hypertensive crisis. Thus, the authors conclude that moclobemide exerts only a slight hypotensive action in hypertensive rats, and differs from other MAO inhibitors in potentiating the pressor effect of tyramine only weakly.

Psychopharmacology (Berl). 1986;88(2):153-7. Related Articles, Links

Moclobemide, a new reversible MAO inhibitor--interaction with tyramine and tricyclic antidepressants in healthy volunteers and depressive patients.

Korn A, Eichler HG, Fischbach R, Gasic S.

Moclobemide is a new, short-acting, reversible MAOI, preferentially affecting type A MAO. We have studied the interaction of moclobemide with tyramine and tricyclic antidepressants in healthy volunteers and depressive patients. Neither tyramine capsules (50 mg) nor cheese and wine meals (65 mg tyramine) produced a significant change in blood pressure and heart rate after single or repeated doses of moclobemide in volunteers. In contrast, after 1 weeks' treatment with tranylcypromine pressure response to cheese and wine meals was severe. Blood pressure sensitivity to IV tyramine was slightly increased (1.5-2 fold; P less than 0.05 versus predrug) during moclobemide treatment in patients and volunteers. This increase was neutralised by concomitant administration of desipramine in volunteers. Amitriptyline was well tolerated when given to patients after or together with moclobemide. In conclusion, moclobemide appears relatively safe with respect to tyramine sensitivity and interaction with tricyclics.

J Clin Psychopharmacol. 1982 Dec;2(6):434-5. Related Articles, Links

Amitriptyline protects patients on MAOIs from tyramine reactions.

Kline NS, Pare M, Hallstrom C, Cooper TB.

Publication Types:

Lancet. 1982 Jul 24;2(8291):183-6. Related Articles, Links

Will amitriptyline prevent the "cheese" reaction of monoamine-oxidase inhibitors?

Pare CM, Kline N, Hallstrom C, Cooper TB.

Administration of amitriptyline greatly diminished the pressor response to intravenous tyramine in patients receiving monoamine-oxidase inhibitors (MAOIs). Dothiepin and trimipramine, however, produced little change in sensitivity to tyramine. It is suggested that a combination of amitriptyline and an MAOI, started together in a modest dose that is then increased, may protect patients against the potential dangers of eating tyramine-containing foods. However, because MAOIs allow a high proportion of ingested tyramine to be absorbed into the systemic circulation, patients treated with MAOIs, even in combination with amitriptyline, should not be encouraged to eat foods containing tyramine.

NB. amitriptyline inhibits the reuptake of NE and 5-HT, dothiepin is a *weak* dual reuptake inhibitor, trimipramine is not a reuptake inhibitor.

What do you think?





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