Some in vitro effects of moclobemide and other MAO inhibitors on responses to sympathomimetic amines.
The use of inhibitors of monoamine oxidase (MAO) in the treatment of some forms of depression has been marred by the occurrence of unpleasant or even fatal side effects. Of these the most serious has been the risk of sudden hypertensive crises following the ingestion of food or drink containing indirectly-acting sympathomimetic amines such as tyramine (cheese effect). This effect, due to long lasting or irreversible inhibition of MAO in the gut and vasomotor neurones is much less obvious with the new generation of reversible inhibitors. Acceptance into clinical practice of these agents will depend upon the provision of clear and unequivocal evidence that there is little or no risk of unexpected cheese effects. The use of in vitro methods has provided a most sensitive way of revealing and measuring any such propensity in these new agents including moclobemide, cimoxatone and toloxatone. Use of isolated smooth muscles, such as the vas deferens and anococcygeus muscles of the rat together with vascular smooth muscle, typified by the perfused mesenteric arterial bed may be used as reliable preliminaries to in vivo and human volunteer studies in an attempt to introduce into clinical medicine an antidepressant that acts through the inhibition of MAO but carries little or no risk of the cheese effect.
Callingham
B A
BA
Department of Pharmacology, University of Cambridge, United Kingdom.
Ovens
R S
RS
D000818:Animals; D001549:Benzamides / Q000633:toxicity*; D001794:Blood Pressure / Q000187:drug effects; D004357:Drug Synergism; D066298:In Vitro Techniques; D020912:Moclobemide; D008996:Monoamine Oxidase Inhibitors / Q000633:toxicity*; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D051381:Rats; D013566:Sympathomimetics / Q000633:toxicity*
D001549:Benzamides; D008996:Monoamine Oxidase Inhibitors; D013566:Sympathomimetics; D020912:Moclobemide