IngentaConnect Chiral selective effects of doxazosin enantiomers on blood pressu...

Authors: MA, Shi-ping¹; REN, Lei-ming; ZHAO, Ding¹; ZHU, Zhong-ning¹; WANG, Miao¹; LU, Hai-gang²; DUAN, Li-hua²

Source: Acta Pharmacologica Sinica, Volume 27, Number 11, November 2006 , pp. 1423-1430(8)

Abstract:

Aim: To study chiral selective effects of doxazosin enantiomers on blood pressure and urinary bladder pressure in anesthetized rats. Methods: In anesthetized rats, the carotid blood pressure, left ventricular pressure of the heart and the urinary bladder pressure were recorded. Results: Administration of S-doxazosin at 0.25, 2.5, 25, and 250 nmol/kg iv produced a dose-dependent decrease in blood pressure, but its depressor effect was significantly weaker than that induced by R-doxazosin and racemic-doxazosin (rac-doxazosin), and the ED₃₀ values (producing a 30% decrease in mean arterial pressure) of R-doxazosin, rac-doxazosin and S-doxazosinwere 15.64,45.93, and 128.81, respectively. Rac-doxazosin and its enantiomers administered cumulatively in anesthetized rats induced a dose-dependent decrease in the left ventricular systolic pressure and ±dp/dt_max, and the potency order of the 3 agents was R-doxazosin >rac-doxazosin >S-doxazosin. Rac-doxazosin and its enantiomers decreased the vesical micturition pressure dose-dependently at 2.5,25, and 250 nmol/kg, and the inhibitory potency among the 3 agents was not significantly different. Conclusion:S-doxazosin decreases the carotid blood pressure and left ventricular pressure of the heart less than R-doxazosin and rac-doxazosin, but its effect on the vesical micturition pressure is similar to R-doxazosin and rac-doxazosin, indicating that S-doxazosin has chiral selectivity between cardiovascular system and urinary system in anesthetized rats.

Keywords: R-doxazosin; S-doxazosin; blood pressure; ventricular pressure; urinary bladder pressure; rat

Document Type: Research article

DOI: 10.1111/j.1745-7254.2006.00443.x

Affiliations: 1: Hebei Medical University School of Pharmacy, Shijiazhuang 050017, China 2: Hebei Professional College in Chemical & Pharmaceutical Sciences, Shijiazhuang 050031, China

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Chiral selective effects of doxazosin enantiomers on blood pressure and urinary bladder pressure in anesthetized rats