An ab initio study of anticonvulsants

Abstract

A systematic theoretical study of anticonvulsant compounds has been performed for the first time, utilizing ab initio molecular orbital techniques. The geometry and pharmacophore charge distribution, the effect of substituents and protonation of the imide nitrogen on the pharmacophore ring charge distribution and drug-receptor interactions have been studied in detail. The results indicate a rigid, typical and highly charged environment on the pharmacophore ring which is not altered by substituents or protonation of the imide nitrogen. The intermolecular interaction calculations indicate that the drug is capable of disrupting normal hydrogen-bonding patterns in lipoproteins or phospholipids. The results also indicate common cellular ions as strong competitors for the binding site.