Maksay G, Pálosi E, Tegyey Z, Otvös L
J Med Chem. 1981 May;24(5):499-502. doi: 10.1021/jm00137a005.
Antimetrazol and muscle-relaxant activities of 11 aliphatic esters of oxazepam were studied as a function of time in mice. The esters given intravenously retained antimetrazol activity, while muscle-relaxant activity was generally decreased. The administration of a dose equivalent to the antimetrazol ED50 resulted in constant oxazepam brain levels for most esters; therefore, the intrinsic anticonvulsant activity of the intact ester is insignificant. The dimethylphenylpropionyl ester appeared to antagonize the effect of oxazepam, since it elevated the free oxazepam level required to achieve the ED50 in the antimetrazol assay. The administration of doses equivalent to the muscle-relaxant ED50 values resulted in no correlation with total brain benzodiazepine levels, suggesting that changes in the selectivity of action are the consequence of different sites of action.
研究了11种奥沙西泮脂肪族酯的抗甲恶唑和肌肉松弛活性随时间在小鼠体内的变化。静脉注射这些酯后仍保留抗甲恶唑活性，而肌肉松弛活性通常会降低。给予相当于抗甲恶唑ED50的剂量后，大多数酯的奥沙西泮脑内水平保持恒定；因此，完整酯的内在抗惊厥活性不显著。二甲基苯基丙酰酯似乎拮抗了奥沙西泮的作用，因为在抗甲恶唑试验中，它提高了达到ED50所需的游离奥沙西泮水平。给予相当于肌肉松弛ED50值的剂量后，与全脑苯二氮䓬水平无相关性，这表明作用选择性的变化是不同作用部位的结果。
