Effects of bepridil on heart mitochondrial membrane and the isolated rat heart preparation.
Bepridil (Cordium) was found to activate rat heart mitochondrial membrane-bound ATPase at concentrations of 10 nmol/l-10 mumol/l. By contrast, oligomycin-sensitive ATPase from beef heart mitochondria was inhibited at concentrations of 1-10 mumol/l. In both systems sensitivity toward the inhibitor oligomycin was reduced. Under the influence of the drug, RCR (coupling degree of electron transport to ATP synthesis), ST3 (oxygen uptake in presence of substrate and ADP) and OPR (oxidative phosphorylation rate, amount of ATP synthesized in mitochondrial metabolic state ST3) values are reduced, indicating partial inhibition of oxidative phosphorylation. At 0.25 mumol/l concentration of bepridil, in the isolated normoxic working rat heart preparation aortic flow was reduced to zero. No changes in oxidative phosphorylation parameters were found in mitochondria isolated from these preparations. In the isolated, working rat heart preparation bepridil at a concentration of 0.05 mumol/l reduced aortic flow to about 75% of its original value. In this preparation, no cardioprotective effects (neither on aortic flow nor on mitochondrial function) could be demonstrated during postischemic reperfusion. It is suggested, that in vitro mitochondrial activities of bepridil are not related to in vivo action of the drug.
D000251:Adenosine Triphosphatases / Q000378:metabolism; D000818:Animals; D015764:Bepridil; D002417:Cattle; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D007202:Indicators and Reagents; D007425:Intracellular Membranes / Q000187:drug effects / Q000201:enzymology; D008929:Mitochondria, Heart / Q000187:drug effects* / Q000201:enzymology; D009840:Oligomycins / Q000494:pharmacology; D010085:Oxidative Phosphorylation / Q000187:drug effects; D010101:Oxygen Consumption / Q000187:drug effects; D011759:Pyrrolidines / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity
D007202:Indicators and Reagents; D009840:Oligomycins; D011759:Pyrrolidines; D015764:Bepridil; D000251:Adenosine Triphosphatases