Oxfenicine is an inhibitor of carnitine palmitoyltransferase 1 (CPT1) and a prodrug form of 4-hydroxyphenylglyoxylic acid.1,2 Oxfenicine is transaminated to 4-hydroxyphenylglyoxylic acid by branched-chain amino acid aminotransferase in rat heart homogenates.3 It inhibits fatty acid oxidation and increases carbohydrate oxidation in isolated rat hearts perfused with palmitate , glucose, and insulin.4 Oxfenicine increases the ex vivo activity of cardiac pyruvate dehydrogenase (PDH) in rats with an ED50 value of 0.3 mmol/kg.1 It reduces increases in plasma levels of lactate and lactate dehydrogenase 1 (LDH-1), markers of ischemic injury, in a dog model of microsphere-induced coronary ischemia when administered at a dose of 0.1 mmol/kg.5
1.Barnish, I.T., Cross, P.E., Danilewicz, J.C., et al.Promotion of carbohydrate oxidation in the heart by some phenylglyoxylic acidsJ. Med. Chem.24(4)399-404(1981) 2.Bielefeld, D.R., Vary, T.C., and Neely, J.R.Inhibition of carnitine palmitoyl-CoA transferase activity and fatty acid oxidation by lactate and oxfenicine in cardiac muscleJ. Mol. Cell. Cardiol.17(6)619-625(1985) 3.Higgins, A.J., Morville, M., Burges, R.A., et al.Oxfenicine diverts rat muscle metabolism from fatty acid to carbohydrate oxidation and protects the ischaemic rat heartLife Sci.27(11)963-970(1980) 4.Burges, R.A., Gardiner, D.G., and Higgins, A.J.Protection of the ischaemic dog heart by oxfenicineLife Sci.29(18)1847-1853(1981)