CAY10665

Isolated neonatal rat cardiomyocytes, which spontaneously beat in culture, are used to evaluate the antiarrhythmic effects of polyunsaturated fatty acids (PUFA). In this model, the ω-3 PUFA eicosapentaenoic acid (EPA, 3-10 μM) reduces the contraction rate of cells, indicating a positive antiarrhythmic effect. Cytochrome P450 metabolites of EPA are more potent, with 17,18-epoxyeicosatetraenoic acid (17,18-EET) reducing contractions at 30 nM. CAY10665 is a bioisostere of 17,18-EET which is approximately 50% more effective at reducing arrhythmic contraction frequency, without affecting amplitude, when tested at 30 nM. This disubstituted oxamide represents a stable analog of 17,18-EET which may be used to study the mechanism of regulation of cardiomyocyte contractility by EPA metabolites.