Molecular Modelling Analysis of the Metabolism of Rasagiline
Rasagiline (RSG) is a second-generation, selective and irreversible inhibitor of monoamine oxidase type B (MAO-B) developed for the treatment of Parkinsons diseases. Molecular modelling analyses based on molecular mechanics, semi-empirical (PM3) and DFT (at B3LYP/6-31G* level) calculations show that both RSG and its metabolite ADN have large LUMO-HOMO energy differences so that they would be kinetically inert. The molecular surfaces RSG and ADN are found to possess neutral, electron-deficient and negatively charged regions so that they may be subject to lyophilic, nucleophilic and electrophilic attacks. However, because of kinetic inertness of the molecules, the rates of the reactions including any adverse reactions with glutathione and nucleobases in DNA are expected to be low. This may explain why RSG and ADN have little side effects.
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