Palea Stefano, Chang David F, Rekik Moez, Regnier Alain, Lluel Philippe
UROsphere, Faculté des Sciences Pharmaceutiques, Ecole Nationale Vétérinaire de Toulouse, Toulouse, France.
J Cataract Refract Surg. 2008 Mar;34(3):489-96. doi: 10.1016/j.jcrs.2007.10.045.
To compare the pharmacologic properties of tamsulosin and alfuzosin in isolated prostatic and iris dilator smooth muscle from pigmented rabbits.
UROsphere Laboratories, Université Paul Sabatier, Toulouse, France.
Prostatic and iris dilator smooth muscle strips were placed in organ baths. A concentration-response curve to phenylephrine was compared before and after incubation with tamsulosin or alfuzosin.
Both drugs were approximately 30 times less potent in iris dilator than prostatic smooth muscle. In the iris, tamsulosin acted as a competitive antagonist starting at the 0.03 microM concentration (pA(2)=7.96). This is in the same range as the maximum plasma concentration after a 0.4 mg dose of tamsulosin in humans (0.025 microM). The antagonistic effect of alfuzosin in the iris was weaker (calculated mean pA(2) value of 5.63+/-0.19). Concentrations with an equipotent antagonistic effect on rabbit iris dilator muscle (3.0 and 10.0 microM) were approximately 100 to 300 times higher than the maximum plasma concentrations after a 10.0 mg dose of alfuzosin in humans (0.032 microM).
Tamsulosin was more effective than alfuzosin at blocking adrenergic contraction of the iris dilator muscle in pigmented rabbits. Both drugs were less potent in the iris than in the prostate, which suggests that an additional iris receptor could be involved. If valid in humans, our results suggest that attainable plasma concentrations of tamsulosin are able to antagonize iris dilator smooth muscle contraction, whereas those of alfuzosin are not. This could explain the higher frequency of intraoperative floppy-iris syndrome in patients treated with tamsulosin than with alfuzosin.
比较坦索罗辛和阿夫唑嗪对有色家兔离体前列腺和平滑肌及虹膜散瞳肌的药理特性。
法国图卢兹保罗·萨巴蒂尔大学泌尿实验室。
将前列腺和平滑肌条置于器官浴槽中。比较用坦索罗辛或阿夫唑嗪孵育前后对去氧肾上腺素的浓度-反应曲线。
两种药物对虹膜散瞳肌的效力均比对前列腺平滑肌的效力弱约30倍。在虹膜中，坦索罗辛从0.03微摩尔浓度开始起竞争性拮抗剂作用（pA(2)=7.96）。这与人类服用0.4毫克坦索罗辛后的最大血浆浓度（0.025微摩尔）处于同一范围。阿夫唑嗪在虹膜中的拮抗作用较弱（计算得出的平均pA(2)值为5.63±0.19）。对家兔虹膜散瞳肌产生等效拮抗作用的浓度（3.0和10.0微摩尔）比人类服用10.0毫克阿夫唑嗪后的最大血浆浓度（0.032微摩尔）高约100至300倍。
在阻断有色家兔虹膜散瞳肌的肾上腺素能收缩方面，坦索罗辛比阿夫唑嗪更有效。两种药物对虹膜的效力均比对前列腺的效力弱，这表明可能涉及额外的虹膜受体。如果在人类中也成立，我们的结果表明，坦索罗辛可达到的血浆浓度能够拮抗虹膜散瞳肌的收缩，而阿夫唑嗪则不能。这可以解释接受坦索罗辛治疗的患者术中虹膜松弛综合征的发生率高于接受阿夫唑嗪治疗的患者。
