Pharmacologcal interactions between nimodipine; a calcium channel blocker, and some opioids; morphine and tramadol

ABSTRACT

This study was designed to evaluate the effect of the calcium channel blocker [CCB] nimodipine "dihydropyridine type" on the antinoeiceptive action of morphine and tramadol and their adverse effects on isolated rabbit hearts. Mice [weight, 20-30 g] were assigned to receive intra peritoneal [IP] one dose of nimodipine, morphine, tramadol and saline and were tested for their effect on the response latency using 55.5°C hot plate. The combinations of nimodipine and other agents also were tested. Nimodipine [800 micro g/kg], morphine [1000 micro g/kg] and tramadol [1600 micro g/kg] yielded increase in thermal threshold. Combined administration of nimodipine with subanalgesic dose of morphine [600 micro g/kg] produced a potent synergy, while combined administration of nimodipine with subanalgesic dose of tramadol [1000 micro g/kg] produced synergistic effect approach that produced by analgesic dose of tramadol alone. Isolated rabbit heart preparations were used to demonstrate the effects of one dose of nimodipine, morphine, tramadol and mammaline ringer solution on myocardial contractility using a modified langendaroffs apparatus. The combinations of nimodipine and other agents also were tested Nimodipine [0.25 micro g/ml], morphine [200 micro g/ml] yielded reduction in rabbit heart contraction, while tramadol [64 micro g/ml] did not yield significant reduction. Combined administration of nimodipine with subclinical concentration of morphine [100 micro g/ml] produced reduction in rabbit heart contraction near to that produced by analgesic dose of morphine alone, while combined administration of nimodipine with subclinical concentration of tramadol [32 micro g/ml] produced reduction in rabbit heart contraction near to that produced by nimodipine alone. This study showed that, CCBs and opioids produced synergistic antinocicepflve effect in response to acute thermal stimulus in animals. Co-administration of nimodipine and subclinical concentration of morphine decreased the detrimental negative inotropic effect of both drugs. These results suggest an important direction for development of acute pain strategies may focus on the voltage-dependent calcium channels in different afferent fibers