Effects of doxazosin enantiomers by different routes of administration on urinary bladder function in guinea pigs

AIM To compare the effects of S-doxazosin, R-doxazosin and rac-doxazosin on urinary bladder function. METHODS The vesical micturition pressure (VMP), micturition threshold pressure (MTP), and intercontraction interval (ICI) in anesthetized guinea pigs were recorded using a PowerLab/8sp ADInstruments data recording and analysis system, and the vesical micturition volume (VMV) was measured simultaneously. RESULTS S-Doxazosin, R-doxazosin and rac-doxazosin (0.08-2.40 mg·kg-1, intraduodenally) decreased the VMP in a dose-dependent manner in anesthetized guinea pigs. S-Doxazosin (intraduodenally) did not affect the MTP, ICI and VMV significantly, while R-doxazosin (intraduodenally) significantly depressed the MTP. R-Doxazosin and rac-doxazosin (intraduodenally) significantly decreased the ICI, and the VMV. S-Doxazosin, R-doxazosin and rac-doxazosin (0.008-0.800 mg·kg-1, iv) decreased the VMP in a dose-dependent manner in anesthetized guinea pigs, and their inhibitory potencies on the VMP were not significantly different. None of the three agents (iv) affected the MTP significantly. S-Doxazosin and R-doxazosin (iv) significantly increased the ICI and the VMV. CONCLUSION Compared with rac-doxazosin and R-doxazosin, S-doxazosin remains the beneficial action on VMP without adverse effects on MTP, ICI and VMV.