Пергексиллин

Использование

Vasodilator (coronary).

Ферментативный ингибитор

This calcium-blocking vasodilator (FW = 277.49 g/mol; CAS 6621-47-2; typically supplied as the maleate or HCl salt), also known as Pexid? and 2- (2,2-dicyclohexylethyl)piperidine, is used to treat angina. It does so by targetting carnitine palmitoyltransferase-1 (CPT-1), an enzyme that controls the access of long chain fatty acids to the mitochondrial site of b-oxidation, showing concentration-dependent inhibition in vitro, using rat cardiac mitochondria, IC50 = 77 μM, and hepatic mitochondria, IC50 = 148 μM. Amiodarone, another drug with anti-anginal properties, likewise inhibits cardiac CPT-1 (IC50 = 228 μM). The rank order of potency for inhibition was malonyl-CoA > 4-hydroxyphenylglyoxylate = perhexiline > amiodarone = monohydroxy-perhexiline. Inhibition was competitive with respect to palmitoyl-CoA but non-competitive inhibition with respect to carnitine. This shifts myocardial metabolism from fatty acid to glucose utilisation which results in increased ATP production for the same O2 consumption and consequently increases myocardial efficiency. (See also Meldonium) Other Target(s): CYP2D6; glutathione S-transferase; Mg2+-ATPase; NADH dehydrogenase; Na+ /K+ -exchanging ATPase; b-oxidation; oxidative phosphorylation; and succinate dehydrogenase.