Hypotensive action and weak potentiation of tyramine effect by moclobemide in rats.
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.
Da Prada
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Pharmaceutical Research Department, F. Hoffmann-La Roche, Basle, Switzerland.
Burkard
W P
WP
D000284:Administration, Oral; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006339:Heart Rate / Q000187:drug effects; D020912:Moclobemide; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D051381:Rats; D014439:Tyramine / Q000494:pharmacology*
D000928:Antidepressive Agents; D001549:Benzamides; D008996:Monoamine Oxidase Inhibitors; D020912:Moclobemide; D014439:Tyramine