A REVERSIBLE MONOAMINE-OXIDASE INHIBITOR, TOLOXATONE - SPECTROPHOTOMETRIC AND MOLECULAR-ORBITAL STUDIES OF THE INTERACTION WITH FLAVIN ADENINE-DINUCLEOTIDE (FAD)

Citation
F. Moureau et al., A REVERSIBLE MONOAMINE-OXIDASE INHIBITOR, TOLOXATONE - SPECTROPHOTOMETRIC AND MOLECULAR-ORBITAL STUDIES OF THE INTERACTION WITH FLAVIN ADENINE-DINUCLEOTIDE (FAD), European journal of medicinal chemistry, 29(4), 1994, pp. 269-277
Citations number
19
Categorie Soggetti
Chemistry Medicinal
ISSN journal
02235234
Volume
29
Issue
4
Year of publication
1994
Pages
269 - 277
Database
ISI
SICI code
0223-5234(1994)29:4<269:ARMIT->2.0.ZU;2-O
Abstract
Toloxatone is a monoamine oxidase A (MAO(A)) inhibitor, marketed as an tidepressant devoid of the undesirable side effects of first-generatio n irreversible monoamine oxidase inhibitors (MAOIs). Its advantages ar ise from the reversible, competitive and specific nature of its inhibi tion. The mechanism for irreversible inhibition of MAO(A) at the molec ular level is known (suicide substrate). A physicochemical study was u ndertaken to establish the mechanism of reversible inhibition by Tolox atone. After determination of structural and electronic properties [6] , experimental and theoretical approaches were used to explore the pos sibility of a physical association between the eutomer R-Toloxatone an d flavin, a cofactor of MAO(A). For this, 2 models of flavin were used . First, the existence of a charge-transfer complex between R-Toloxato ne 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 complement ary electronic zones of R-Toloxatone and SCH3-lumiflavin for a defined relative orientation.