Subscribe Now Subscribe Today
Science Alert
 
Blue
   
Curve Top
Journal of Pharmacology and Toxicology
  Year: 2006 | Volume: 1 | Issue: 4 | Page No.: 369-375
DOI: 10.3923/jpt.2006.369.375
 
Facebook Twitter Digg Reddit Linkedin StumbleUpon E-mail

Molecular Modelling Analysis of the Metabolism of Modafinil

Fazlul Huq

Abstract:
Modafinil (MDF) is a unique wake-promoting agent that may be used in a variety of conditions including narcolepsy, obstructive sleep apnea and shift work sleep disorder. The mechanism of action of MDF is believed to be different from those of CNS stimulants such as amphetamine or methylphenidate. The drug is primarily metabolized in the liver and eliminated mainly as metabolites in the urine. It is based largely on amide hydrolysis and to a smaller extent proceeds via cytochrome P450-mediated oxidative pathways. Molecular modelling analyses based on molecular mechanics, semi-empirical (PM3) and DFT (at B3LYP/6-31G* level) calculations show that MDF and all its metabolites have large LUMO-HOMO energy differences so that they would be kinetically inert. The molecular surfaces MDF and all its metabolites are found to have electron-deficient regions so that they may be subject to nucleophilic attacks such as those by glutathione and nucleobases in DNA. Reaction with glutathione induces cellular toxicity compromising the antioxidant status of the cell whereas oxidation of nucleobases in DNA causes DNA damage. The kinetic inertness of the molecules may however mean that the rates of such adverse reactions may not be significant.
PDF Fulltext XML References Citation Report Citation
How to cite this article:

Fazlul Huq , 2006. Molecular Modelling Analysis of the Metabolism of Modafinil. Journal of Pharmacology and Toxicology, 1: 369-375.

DOI: 10.3923/jpt.2006.369.375

URL: https://scialert.net/abstract/?doi=jpt.2006.369.375

COMMENT ON THIS PAPER
 
 
 

 

 
 
 
 
 
 
 
 
 

 
 
 
 
 
 
 

Curve Bottom