软性药物15：甲基东莨菪碱苯基琥珀酸软性类似物作为短效散瞳剂的散瞳活性和经角膜渗透

Soft drugs 15: mydriatic activity and transcorneal penetration of phenylsuccinic soft analogs of methscopolamine as short acting mydriatics.

作者信息

Kumar G N, Hammer R H, Wu W M, Bodor N S

机构信息

Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville 32610.

出版信息

Curr Eye Res. 1993 Jun;12(6):501-6. doi: 10.3109/02713689309001828.

DOI:10.3109/02713689309001828

PMID:8359027

Abstract

Soft drug analogs of methscopolamine (4 a-c) were tested for mydriatic activity in rabbits' eyes. After unilateral administration of equieffective doses, the AUC24hrs and the mydriatic recovery times were found to be significantly lower with the soft drugs compared to methscopolamine. At equieffective doses, the AUC24hrs for soft drugs ranged from 22.4% to 60% of that of methscopolamine. Significant dilation of the untreated eye was observed with methscopolamine but not with the soft drugs after unilateral administration. Soft drug 4a exhibited only 10.4% of the AUC6hrs (untreated eye) of that of methscopolamine. Shorter durations of mydriatic action combined with potentially reduced systemic side effects make these compounds candidates for further study. In vitro rabbit transcorneal penetration of soft analog 4a was found to be significantly higher than methscopolamine.

摘要

对甲基东莨菪碱的软药类似物（4a - c）进行了兔眼散瞳活性测试。单侧给予等效剂量后，发现与甲基东莨菪碱相比，软药的24小时药时曲线下面积（AUC24hrs）和散瞳恢复时间显著更低。在等效剂量下，软药的AUC24hrs为甲基东莨菪碱的22.4%至60%。单侧给药后，甲基东莨菪碱可观察到未治疗眼出现明显散瞳，但软药未出现这种情况。软药4a的6小时药时曲线下面积（未治疗眼）仅为甲基东莨菪碱的10.4%。散瞳作用持续时间较短且潜在的全身副作用可能减少，使得这些化合物成为进一步研究的候选对象。发现软类似物4a在体外兔角膜的渗透明显高于甲基东莨菪碱。