BISARAMIL AND ANTIARRHYTHMICS AS INHIBITORS OF FREE-RADICAL GENERATION

The aim of this study was to investigate the effect of bisaramil-an an tiarrhythmic drug under clinical trials-on free radical generation of isolated polymorph neutrophil granulocytes (PMN) and furthermore to co mpare its activity to that of well-known antiarrhythmics which have di fferent modes of action, PMNs were isolated from healthy beagle dogs, and superoxide radical generation was induced by phorbol-myristate-ace tate. Stimulated free radical generation capacity of PMNs and the time lag necessary for the initiation of free radical production were meas ured. All Compounds were used at the concentrations of 10, 25, 50, 75, 100 mu g ml(-1). None of the antiarrhythmics stimulated by itself the free radical generation. Bisaramil exerted concentration dependent in hibitory effect on PMA-stimulated free radical generation and prolonge d the time lag concentration dependently. At the investigated concentr ation range of antiarrhythmics only propafenon, mexiletine and diltiaz em showed similar activity to bisaramil, but clear concentration depen dency could not be seen in any of the cases. According to the results of this study inhibition of the stimulated free radical production of isolated PMNs cannot be closely connected merely to either membrane st abilizing or Ca-antagonistic activity of drugs. In vitro and earlier m easured in vivo inhibitory action of bisaramil on free radical generat ion indicate a possible cardioprotective effect existing independently from its antiarrhythmic one. This observation may be important in out lining of the clinical indication field of bisaramil, and may be usefu l in the treatment of reperfusional damage. (C) 1997 The Italian Pharm acological Society.