Lien E J, Liao R C, Shinouda H G
J Pharm Sci. 1979 Apr;68(4):463-5. doi: 10.1002/jps.2600680418.
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.
对16种市售抗癫痫药物的抗惊厥和中枢神经系统抑制活性进行了回归分析。对于最大电休克惊厥试验和戊四氮惊厥阈值试验，仅在去除地西泮、氯硝西泮和卡马西平后才获得良好的相关性；对于半数中毒剂量（转子杆共济失调），使用log MW、log P和偶极矩（μ）项，所有16种化合物都可以包含在一个单一方程中。对于7-取代的1,4-苯二氮䓬酮的抗惊厥活性，在三种不同试验中对大多数所研究的衍生物而言，π与哈米特σ常数的抛物线方程给出了尚可的相关性。基于所获得的相关性，提出了进一步的分子修饰建议。首次在1,4-二氧六环中测量了7种临床使用的抗癫痫药物的偶极矩。
