Soft drugs 15: mydriatic activity and transcorneal penetration of phenylsuccinic soft analogs of methscopolamine as short acting mydriatics.
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.
Kumar
G N
GN
Department of Medicinal Chemistry, College of Pharmacy, University of Florida, Gainesville 32610.
Hammer
R H
RH
Wu
W M
WM
Bodor
N S
NS
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003315:Cornea / Q000378:metabolism*; D008297:Male; D009184:Mydriatics / Q000493:pharmacokinetics*; D019832:N-Methylscopolamine; D010276:Parasympatholytics / Q000493:pharmacokinetics* / Q000494:pharmacology; D011680:Pupil / Q000187:drug effects*; D011817:Rabbits; D012602:Scopolamine Derivatives / Q000493:pharmacokinetics* / Q000494:pharmacology; D013386:Succinates / Q000493:pharmacokinetics*
D009184:Mydriatics; D010276:Parasympatholytics; D012602:Scopolamine Derivatives; D013386:Succinates; C017625:2-phenylsuccinate; D019832:N-Methylscopolamine