Monoamine oxidase A (MAO A) catalyses the oxidation of both neurotransmitter and ingested amines. The mechanism of catalysis involves the covalently bound FAD cofactor. Although substrates and inhibitors alter the thermodynamic and kinetic properties of the flavin, how the ligands interact with the flavin is unknown. This work characterises the spectral changes that occur on inhibitor binding to MAO A and examines how the binding influences the flavin. The inhibitors, D-amphetamine, harmine, tetrindole, and befloxatone all induce similar (but not identical) changes in the spectrum of MAO A, consistent with stacking of inhibitor with the flavin in the active site. D-Amphetamine, harmine, and tetrindole stabilise the semiquinone form of FAD during reduction of MAO A by dithionite and no further reduction of these inhibitor-MAO A complexes has been observed. In contrast, semiquinone is never observed during reduction of the befloxatone-MAO A complex. Instead, partial reduction directly to the FADH(2) form occurs extremely slowly. Thus, inhibitor binding has a strong, structure-dependent influence on the environment of the flavin that alters its electronic properties.

01 Aug 2000·Bulletin of Experimental Biology and MedicineQ4 · MEDICINE

Hemodynamic effects of tetrindol in alert normotensive mice and rats after blockade of nitric oxide synthesis

Q4 · MEDICINE

Article

Author: Korshunov, V. A. ; Ivashev, M. N. ; Dugin, S. F. ; Medvedev, O. S. ; Murashev, A. N.

Single intravenous injection of antidepressant tetrindol (1 and 10 mg/kg), a reversible monoamine oxidase A inhibitor, dose-dependently decreased heart rate and mean arterial pressure (in a concentration of 10 mg/kg) in alert NMRI mice and Sprague-Dawley rats. Nitric oxide synthase blockade with L-NAME attenuated tetrindol-induced bradycardia in rats and completely abolished this effect in mice.

01 Jan 1996·Zhurnal nevrologii i psikhiatrii imeni S.S. Korsakova

[The Russian antidepressant tetrindole].

Article

Author: Muzychenko, A P ; Mashkovskiĭ, M D ; Andreeva, N I ; Golovina, S M

100 Deals associated with Tetrindol

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