Isobolographic analysis of the interaction between fenoldopam and levodopaon arterial blood pressure of the rat

Fenoldopam (PD) and levodopa (LD) injected intravenously in rats in a noncu mulative schedule induced dose-dependent reductions in mean arterial blood pressure. The doses that induced a 50% reduction in the initial control mea n arterial pressure (referred as ED50) were calculated by linear regression analysis of the corresponding parallel dose-response curves and were 0.88 and 0.068 mg/kg, respectively. The interaction between the effects of FD an d LD on pressure reduction was evaluated by simultaneous administration of different fixed ratios of FD and LD (16:1) and obtaining a dose-response cu rve. An isobolographic analysis was then performed, which showed that the e xperimental point for the effect of the simultaneous administration of FD a nd LD was significantly different from the theoretically calculated additiv e point, denoting supradditivity. It was concluded that the effect of the c ombination of FD and LD on mean blood pressure reduction was synergic and w as probably due to an activation of D-1 vascular receptors by both drugs, i n conjunction with an activation of beta(2) adrenoceptors by LD and a block ing action of FD on postsynaptic alpha(1)-adrenoceptors.