VERAPAMIL ENHANCES THE INHIBITORY EFFECT OF DICLOFENAC ON THE CHEMILUMINESCENCE OF HUMAN POLYMORPHONUCLEAR LEUKOCYTES AND CARRAGEENAN-INDUCED RATS PAW EDEMA

Diclofenac dose-dependently (1.25, 2.5 and 5 mg/kg, i.p.) inhibited the oedema produced by carrageenan in the rat's paw. This anti-inflammatory effect was enhanced by the co-administration of various doses (10, 20, and 30 mg/kg i.p.) of verapamil. Diclofenac or the calcium channel blocker, verapamil, when added separately, inhibited the chemiluminescence (CL) response of isolated human polymorphonuclear leukocytes (PMNs) stimulated by either the soluble agent, phorbol myristate acetate, (PMA) or by particulate opsonized zymosan (OPZ) in a dose-dependent manner. When verapamil was combined with diclofenac, in vitro, the inhibitory effect on PMA or OPZ-induced CL response was synergistic. This inhibitory effect of either diclofenac or verapamil on the isolated PMNs was readily reversible when the PMNs were washed with phosphate buffered saline (PBS). Additionally, diclofenac or verapamil did not significantly affect the viability of PMNs. It is concluded that verapamil enhances the anti-inflammatory effect of diclofenac in vivo and potentiates its inhibitory effect on the CL of isolated human PMNs in vitro.