Woodard P A, Winwood D, Brewster M E, Estes K S, Bodor N
Center for Drug Design and Delivery, University of Florida, J. Hillis Miller Health Center, Gainesville 32610.
Drug Des Deliv. 1990 May;6(1):15-28.
A dihydropyridine in equilibrium with pyridinium salt redox system was applied to effect brain delivery of gamma-aminobutyric acid (GABA) derivatives and analogues. The redox system allows the lipophilic dihydropyridine conjugates to penetrate the blood brain barrier, whereas corresponding oxidized pyridinium forms are retained in the brain for an extended period and rapidly eliminated from the periphery. The most promising compound was the GABA benzyl ester-CDS (1a, Scheme I). It had an ED50 of 15.8 mg/kg (i.v.) in protecting mice against maximal electroconvulsive shock-induced tonic hind-leg extension.
一种与吡啶鎓盐氧化还原系统处于平衡状态的二氢吡啶被用于实现γ-氨基丁酸（GABA）衍生物及类似物的脑内递送。该氧化还原系统使亲脂性的二氢吡啶缀合物能够穿透血脑屏障，而相应的氧化吡啶鎓形式则在脑内长时间留存，并从外周迅速清除。最有前景的化合物是GABA苄酯-CDS（1a，方案I）。在保护小鼠免受最大电惊厥休克诱导的强直性后腿伸展方面，其静脉注射的半数有效剂量（ED50）为15.8 mg/kg。
