THE ANTINOCICEPTIVE EFFECT OF MOCLOBEMIDE IN MICE IS MEDIATED BY NORADRENERGIC PATHWAYS

Moclobemide is an antidepressant which affects the monoaminergic neuro transmitter system through a reversible inhibition of monoamine oxidas e (MAO), preferentially type A. We examined the antinociceptive effect s of moclobemide alone and in conjunction with specific opioid, adrene rgic and serotonergic antagonists, using the mouse-tail flick test. In traperitoneal moclobemide produced a dose-dependent antinociceptive ef fect with an ED50 Of 69.1 mg/kg. Tests with selective antagonists yiel ded positive results only for yohimbine (P < 0.001), implying a noradr energic mechanism of action in the moclobemide antinociceptive effect. This was confirmed by the coadministration of moclobemide with inacti ve doses of prototype agonists of the opioid, adrenergic and serotoner gic systems. Only clonidine, an alpha 2 agonist, significantly shifted (8-fold) the dose response curve of moclobemide. We conclude that the re is a selective involvement of the alpha 2 adrenergic pathways in th e moclobemide-induced antinociceptive effect and a lesser involvement (if any) of the opioid, serotonergic and alpha 1 adrenergic mechanisms . More research is needed to establish a possible role for moclobemide in pain management. (C) 1998 Published by Elsevier Science Ireland Lt d. All rights reserved.