The dose of nicorandil in men predicted from the inhibition of MAO activity by organic nitrates.
The effect of N-(2-hydroxyethyl)-nicotinamide nitrate ester (nicorandil) on rat heart monoamine oxidase (MAO) was investigated in vitro. MAO activity was assayed by the isotopic method with 14C-tryptamine as substrate. Nicorandil significantly inhibited MAO activity of rat heart mitochondria. The effect of nicorandil on the enzymatic kinetics of MAO of rat heart mitochondria indicates that the anti-anginal drug acts as a competitive inhibitor of MAO. The inhibitor constant (Ki) of nicorandil was 4.93 mmol/l. The Ki of nicorandil was fitted to the formula derived from the relationship between the Ki values of glyceryl trinitrate, erythrytol tetranitrate, mannitol hexanitrate and isosorbide dinitrate and the dose of these drugs recommended to relieve anginal pain in patients. The dose of nicorandil was 0.071 mmol (15.0 mg at a time). This value agreed with the clinical dose for patients (10--20 mg at a time).
D000818:Animals; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D008930:Mitochondria, Liver / Q000201:enzymology*; D008996:Monoamine Oxidase Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D009536:Niacinamide / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D020108:Nicorandil; D009566:Nitrates / Q000008:administration & dosage* / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014363:Tryptamines / Q000378:metabolism
D008996:Monoamine Oxidase Inhibitors; D009566:Nitrates; D014363:Tryptamines; D009536:Niacinamide; D020108:Nicorandil