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  • Title: R and S enantiomers of oxybutynin: pharmacological effects in guinea pig bladder and intestine.
    Author: Kachur JF, Peterson JS, Carter JP, Rzeszotarski WJ, Hanson RC, Noronha-Blob L.
    Journal: J Pharmacol Exp Ther; 1988 Dec; 247(3):867-72. PubMed ID: 2849672.
    Abstract:
    Oxybutynin (Ditropan) is widely utilized in treatment of incontinence due to neurogenic bladder dysfunction. We prepared its R and S enantiomers and evaluated their antimuscarinic, Ca++-channel antagonistic and spasmolytic effects in guinea pig detrusor strips and ileal longitudinal muscle. Ussing chambers were used to assess inhibition of carbachol-induced mucosal Cl-secretion in vitro. The enantiomers and the racemate were also tested in in vivo preparations for local anesthetic activity and for antimuscarinic activity in the slow filling cystometrogram. Stereoselective antimuscarinic effects [R)OXY:(R/S)OXY:(S)OXY) were evident for isolated ileal longitudinal (0.12:1.0:4.5) and bladder detrusor muscle (0.5:1.0:13) isolated ileal mucosa (0.2:1:8.9) and acetylcholine stimulated phosphoinositide turn-over in vitro (0.24:1.0:39). Stereoselectivity was also evident for the volume-induced contractions of the cystometrogram in vivo (0.7:1:15). In contrast, no stereoselectivity was observed for Ca++-channel antagonism, spasmolytic and local anesthetic properties of (R/S)OXY and its enantiomers.
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