AN AB-INITIO STUDY OF ANTICONVULSANTS

A systematic theoretical study of anticonvulsant compounds has been pe rformed for the first time, utilizing ab initio molecular orbital tech niques. The geometry and pharmacophore charge distribution, the effect of substituents and protonation of the imide nitrogen on the pharmaco phore ring charge distribution and drug-receptor interactions have bee n 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 disrupti ng normal hydrogen-bonding patterns in lipoproteins or phospholipids. The results also indicate common cellular ions as strong competitors f or the binding site.