Development of novel anti-arrhythmic drugs

Dietary fish-oil omega-3 polyunsaturated fatty acids (n-3 PUFAs) such as eicosapentaenoic acid (EPA) protect against arrhythmia and sudden cardiac death by so far largely unknown mechanisms. We found that these beneficial effects are mediated by cytochrome P450 enzymes that convert n-3 PUFAs to (n-3)-epoxy-eicosanoids. Based on these findings, we are now going (1) to develop a new class of anti-arrhythmic drugs taking 17,18-epoxyeicosatetraenoic acid, i.e. the bioactive metabolite derived from EPA, as the lead compound and (2) to identify the putative G protein-coupled receptor that specifically interacts with (n-3)-epoxy-eicosanoids and serves as target for the novel anti-arrhythmic drugs.