EFFECT OF PIRIBEDIL AND ITS METABOLITE, S584, ON BRAIN LIPID-PEROXIDATION IN-VITRO AND IN-VIVO

We studied the effect of piribedil 3,4-methylendioxybenzyl-4-(2-pyrimi dyl)piperazine) and its catechol metabolite, S584 3,4-dihydroxybenzyl- 4-(2-pyrimidinyl)-piperazine), on rat brain lipid peroxidation (a) in vitro in rat synaptosomes and cortical slices after induction of an ox idative stress and (b) in vivo in mouse brain after short-term exposur e (two and three 4-h cycles) to O-2/CO2 (95%:5%). The metabolite (10(- 4)-10(-5) M), but not piribedil, prevented Fe3+-stimulated lipid perox idation in rat synaptosomes and in rat cortical slices incubated with high oxygen concentrations. Piribedil (7.5 and 30 mg/kg, orally), coun teracted the increase in thiobarbituric reactive substances in the bra in of mice only when these were exposed to two or three cycles of a hi gh oxygen concentration. S584 (30 mg/kg, orally) reduced thiobarbituri c acid reactive substances in brain in mice exposed either to air (con trol) or to three cycles of a high oxygen concentration. These results suggest that piribedil has an antiperoxidative effect in brain, which may be partly related to the in vivo formation of the catechol metabo lite, S584. (C) 1997 Elsevier Science B.V.