Improved delivery through biological membranes. XXI. Brain-targeted anti-convulsive agents.

Drug design and delivery Pub Date : 1990-05-01
P A Woodard, D Winwood, M E Brewster, K S Estes, N Bodor
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引用次数: 0

Abstract

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.

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改善通过生物膜的输送。第二十一章。脑靶向抗惊厥药。
采用二氢吡啶与吡啶盐氧化还原平衡体系对γ -氨基丁酸(GABA)衍生物及类似物的脑递送进行了研究。氧化还原系统允许亲脂性二氢吡啶偶联物穿透血脑屏障,而相应的氧化吡啶形式在大脑中保留较长时间并迅速从外周消除。最有希望的化合物是GABA苄基酯- cds (1a,方案一),其ED50为15.8 mg/kg (i.v),可保护小鼠免受最大电休克引起的强直性后腿伸展。
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