Department of Urology, Faculty of Medical Science, University of Fukui, Eiheiji, Fukui, Japan.
Int J Urol. 2011 Dec;18(12):836-43. doi: 10.1111/j.1442-2042.2011.02868.x. Epub 2011 Oct 13.
To investigate the efficacy and safety of a combination treatment with α(1)-blockers and antimuscarinics for detrusor overactivity in rats.
Rats with detrusor overactivity caused by a cerebral infarction were divided into four groups that received an i.v. administration of tamsulosin (0.1-1000 µg/kg); solifenacin (0.01-0.3 mg/kg); combined low doses of tamsulosin (0.008, 0.1 µg/kg) and solifenacin (0.01 mg/kg); or solifenacin (0.1, 0.3, 1.0 mg/kg) at 1-h intervals during the continuous administration of tamsulosin (0.01 µg/kg/h).
Both tamsulosin alone and solifenacin alone significantly increased bladder capacity in cerebral infarcted rats, but these effects were reduced in rats pretreated with resiniferatoxin. The combined low dose of tamsulosin and solifenacin resulted in a significant increase in bladder capacity compared to mono-administration of 0.01 mg/kg solifenacin (68.8 vs 19.8% of control value, respectively). In the group receiving solifenacin at 1-h intervals, solifenacin dose-dependently decreased bladder contraction duration and a significant reduction in bladder contraction pressure (by 35.0% of control value) was found at the highest dose (1.0 mg/kg). However, no reduction in bladder contraction duration was found even at the highest dose of solifenacin when co-administered with tamsulosin.
α(1)-Blockers and antimuscarinic agents have an additive ameliorative effect on detrusor overactivity when co-administered at low doses. α(1)-Blockers prevent the reduction in bladder contraction duration induced by a high-dose administration of antimuscarinic agents.
研究α(1)-受体阻滞剂和抗毒蕈碱药物联合治疗大鼠逼尿肌过度活动的疗效和安全性。
将因脑梗死导致逼尿肌过度活动的大鼠分为四组，分别静脉注射坦索罗辛（0.1-1000μg/kg）；索利那新（0.01-0.3mg/kg）；联合低剂量坦索罗辛（0.008、0.1μg/kg）和索利那新（0.01mg/kg）；或在坦索罗辛（0.01μg/kg/h）持续输注期间，每隔 1 小时给予索利那新（0.1、0.3、1.0mg/kg）。
坦索罗辛单独使用和索利那新单独使用均显著增加脑梗死大鼠的膀胱容量，但预先给予菝葜毒素的大鼠的这些作用减弱。与单独给予 0.01mg/kg 索利那新相比，联合使用低剂量坦索罗辛和索利那新可显著增加膀胱容量（分别为对照值的 68.8%和 19.8%）。在间隔 1 小时给予索利那新的组中，索利那新剂量依赖性地降低膀胱收缩持续时间，并且在最高剂量（1.0mg/kg）时发现膀胱收缩压显著降低（为对照值的 35.0%）。然而，当与坦索罗辛联合使用时，即使给予最高剂量的索利那新，也未发现膀胱收缩持续时间的缩短。
当联合使用低剂量时，α(1)-受体阻滞剂和抗毒蕈碱药物对逼尿肌过度活动具有相加的改善作用。α(1)-受体阻滞剂可防止抗毒蕈碱药物高剂量给药引起的膀胱收缩持续时间缩短。
