アルコール依存症と薬物依存のジャーナル
オープンアクセス
ISSN: 2329-6488
ISSN: 2329-6488
Olha Kyslova*
Background: The aim of this investigation was to study the effect of N-phenyl-N-(1-cyclopropylethyl) nicotinamide and its possible metabolites-hydrochlorides of N-(1-cyclopropylethyl) amine and N-phenyl-N-(1-cyclopropylethyl) amine on the ethanol oxidation enzymes activity in vitro, as well as the kinetics of their interaction.
Methods: The studies were performed using alcohol dehydrogenase and aldehyde dehydrogenase is enzyme forms of rat liver subcellular fractions, which were obtained by differential centrifugation. Enzyme activity was determined spectrophotometrically. The kinetic nature of enzymes interaction with nicotinamide derivative was investigated in the concentration range of 25 μM-75 μM. The obtained results were processed by the Line weaver-Burk method.
Results: Studies have shown that N-phenyl-N-(1-cyclopropylethyl) nicotinamide reduced the rate of the reverse alcohol dehydrogenase reaction in the presence of NADH by 46% with an inhibition constant of 53 μM. Soluble mitochondrial aldehyde dehydrogenase activity was inhibited by 50% with an inhibition constant of 108 μM. The kinetic nature of the substituted nicotinamide interaction with enzymes at saturating concentrations of reaction cofactors NADH and NAD+ was quite complex. Allosteric effects can play a significant role in enzymatic activity. Possible metabolites of the test compound, hydrochlorides of N-(1-cyclopropylethyl) amine and N-phenyl-N-(1- cyclopropylethyl) amine, didn’t significantly alter the ethanol metabolic enzymes activity.
Conclusions: A new inhibitor of the rate of the reverse alcohol dehydrogenase reaction and the activity of the soluble mitochondrial is enzyme form of aldehyde dehydrogenases, which alter the ethanol metabolism and lead to the acetaldehyde accumulation in the body, has been identified. N-phenyl-N-(1-cyclopropylethyl) nicotinamide can be used as a potential anti-alcohol drug with sensitizing action.