QUANTITATIVE STRUCTURE-ACTIVITY-RELATIONSHIPS AND DIPOLE-MOMENTS OF ANTICONVULSANTS AND CNS DEPRESSANTS

The anticonvulsant and CNS‐depressant activities of 16 commercially available antiepileptics were subjected to regression analysis. For the maximal electroshock seizure test and pentylenetetrazol seizure threshold test, good correlations were obtained only after diazepam, clonazepam, and carbamazepam were deleted; for the median toxic dose (rotorod ataxia), all 16 compounds can be included in one single equation using log MW, log P, and dipole moment (μ) terms. For the anticonvulsant activities of 7‐substituted 1,4‐benzodiazepinones, a parabolic equation of π combined with the Hammett π constant gave fair correlations for most derivatives examined in three different tests. Based upon the correlations obtained, further molecular modifications are suggested. The dipole moments of seven clinically used antiepileptic drugs were measured in 1,4‐dioxane for the first time. Copyright © 1979 Wiley‐Liss, Inc., A Wiley Company