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