Review, reevaluation, and new results in quantitative structure-activity studies of anticonvulsants.
This paper reviews and reevaluates all of the published QSAR treatments of anticonvulsants and extends them to a new relationship. This reveals that in almost all cases, the Clog P relationship plays a significant part in the QSAR relationship whether the data stems from receptor to whole animal studies. In some cases the steric factors (B5, B1, and L) are important and, in one case, the log VW relationship is of marginal importance. Electronic effects, except for the Hammett's constant sigma, are comparatively unimportant. This suggests that the receptors involved possess a special stereochemical and electronic feature: The aromatic ring and the nitrogen moieties (e.g., an amide group) are the primary binding groups. The study shows that log P, as calculated by the Clog P program, is suitable for this form of QSAR study. Log Po of 2 was found to be ideal for passive penetration of these agents into the CNS.
Hadjipavlou-Litina
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Department of Pharmaceutical Chemistry, School of Pharmacy, Aristotelian University of Thessaloniki, Greece. Hadjipav@pharm.auth.gr
D000818:Animals; D000927:Anticonvulsants / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D004827:Epilepsy / Q000145:classification / Q000188:drug therapy; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000927:Anticonvulsants