Effects of 3-Hydroxypyridine and Succinic Acid Derivatives on Monoamine Oxidase Activity In Vitro

Abstract

The effects of original Russian 3-hydroxypyridine and succinic acid derivatives (emoxypine, Reamberin, and Mexidol) on monoamine oxidase (MAO-A and MAO-B) activity in rat liver were studied in vitro. The study drugs used in vitro at concentrations in the pharmacokinetic range (10 9 to 10 6 M), were found to have MAO-modulating actions, the directions depending on their chemical structural properties. The isolated 3-hydroxypyridine derivative emoxypine decreased MAO-A activity by 34 – 44% and MAO-B activity by 9 – 10% (p < 0.05 in both cases). The succinic acid derivative Reamberin increased MAO-A activity by 2-3% and MAO-B activity by 14% (p < 0.05 in both cases). Mexidol, which is a derivative of both 3-hydroxypyridine and succinic acid, decreased MAO-A activity by 13% and MAO-B activity by 4% (p < 0.05 in both cases). The 2-ethyl-3-methyl-3-hydroxypyridinium cation and the succinate anion were antagonists in terms of their MAO-modulating actions. Combining these antagonist ions into the structure of Mexidol led to complete loss of the MAO-stimulating effect of the succinate part and a significant reduction in the MAO-inhibiting action of the 3-hydroxypyridine component.