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达非那新对雌性和雄性兔膀胱过度活动症的影响。

The effect of darifenacin on overactive bladders in female and male rabbits.

作者信息

Levin Robert M, Juan Yung-Shun, Whitback Catherine, Perez-Martinez Franciso C, Lin Wei-Yu

机构信息

Stratton Veterans Affairs Medical Center, Albany, NY, USA.

出版信息

Int Urol Nephrol. 2008;40(2):303-9. doi: 10.1007/s11255-007-9251-5.

Abstract

Our current study utilized a model of bladder instability to compare the effectiveness of darifenacin, a selective m3 muscarinic antagonist, at inhibiting overactive bladder (OAB) dysfunction in both male and female rabbits. Twenty-four male and female NZ white rabbits were used for this experiment. Each rabbit was anesthetized and the carotid artery was cannulated for blood pressure (BP) monitoring and the left femoral artery was cannulated for acetylcholine (Ach) administration. The bladder dome was catheterized for monitoring bladder pressure and for cystometry. A ligature was placed around the urethra just distal to the bladder to induce OAB. After OAB developed, the response to four IV doses of darifenacin (0.003; 0.01; 0.03; 0.09 mg/kg) evaluated for their effects. Darifenacin: (1) was an equally potent inhibitor of the contractile response of both sexes to intra-arterial Ach, (2) had no effects on BP, (3) was a potent inhibitor of the frequency of OAB, but had a significantly less potent effect on the amplitude, and (4) Darifenacin showed a greater potency in the female rabbits than in the males. These studies provide support for the use of darifenacin in the treatment of OAB.

摘要

我们目前的研究采用膀胱不稳定模型,比较选择性M3毒蕈碱拮抗剂达非那新在抑制雄性和雌性兔膀胱过度活动症(OAB)功能障碍方面的有效性。本实验使用了24只雄性和雌性新西兰白兔。每只兔子均麻醉后,将颈动脉插管用于监测血压(BP),左股动脉插管用于注射乙酰胆碱(Ach)。膀胱顶部插管用于监测膀胱压力和进行膀胱测压。在膀胱远端的尿道周围放置结扎线以诱导OAB。OAB形成后,评估静脉注射四次达非那新(0.003;0.01;0.03;0.09 mg/kg)的反应及其效果。达非那新:(1)对两性动脉内注射Ach的收缩反应具有同等效力的抑制作用;(2)对血压无影响;(3)是OAB频率的强效抑制剂,但对幅度的抑制作用明显较弱;(4)达非那新在雌性兔中的效力高于雄性兔。这些研究为达非那新用于治疗OAB提供了支持。

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