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 (mu) terms. For the anticonvulsant activities of 7-substituted 1,4-benzodiazepinones, a parabolic equation of pi combined with the Hammett sigma 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.
D000818:Animals; D000927:Anticonvulsants / Q000494:pharmacology*; D002492:Central Nervous System Depressants / Q000494:pharmacology*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D004597:Electroshock; D010433:Pentylenetetrazole / Q000037:antagonists & inhibitors; D004856:Postural Balance / Q000187:drug effects; D013329:Structure-Activity Relationship
D000927:Anticonvulsants; D002492:Central Nervous System Depressants; D010433:Pentylenetetrazole