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Journal of Pharmacology and Toxicology

Year: 2008  |  Volume: 3  |  Issue: 1  |  Page No.: 27 - 33

Molecular Modelling Analysis of the Metabolism of Venlafaxine

Fazlul Huq

Abstract

Venlafaxine (VEN) is a new phenylethylamine bicyclic antidepressant whose activity is due to inhibition of neuronal uptake of norepinephrine, serotonin and dopamine. Molecular modelling analyses based on molecular mechanics, semi-empirical (PM3) and DFT (at B3LYP/6-31G* level) calculations show that VEN and its major metabolites have high LUMO-HOMO energy differences ranging from 5.0 to 5.7 eV, indicating that the compounds would all be kinetically inert. The molecular surface of neither VEN nor any of its metabolites is found to abound in electron-deficient regions so that the compounds may not react with cellular nucleophiles such as glutathione and nucleobases in DNA. This means the compounds may not induce cellular toxicity associated with glutathione depletion and DNA damage associated with oxidation of nucleobases.

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