F. Moureau, J. Wouters, D. P. Vercauteren
1994
Citations
0
Influential Citations
42
Citations
Journal
European Journal of Medicinal Chemistry
Abstract
Abstract Toloxatone is a monoamine oxidase A (MAO A ) inhibitor, marketed as antidepressant devoid of the undesirable side effects of first-generation irreversible monoamine oxidase inhibitors (MAOIs). Its advantages arise from the reversible, competitive and specific nature of its inhibition. The mechanism for irreversible inhibition of MAO A at the molecular level is known (suicide substrate). A physicochemical study was undertaken to establish the mechanism of reversible inhibition by Toloxatone. After determination of structural and electronic properties [6], experimental and theoretical approaches were used to explore the possibility of a physical association between the eutomer R -Toloxatone and flavin, a cofactor of MAO A . For this, 2 models of flavin were used. First, the existence of a charge-transfer complex between R -Toloxatone and riboflavin was demonstrated by electron absorption spectroscopy. Second, ab initio Hartree-Fock calculations of frontier orbitals and electrostatic potentials confirm the favourable overlap of complementary electronic zones of R -Toloxatone and SCH 3 -lumiflavin for a defined relative orientation.