具有钙拮抗活性的抗胆碱能药物NS-21对尿频大鼠模型下尿路功能的影响。

Effect of NS-21, an anticholinergic drug with calcium antagonistic activity, on lower urinary tract function in a rat model of urinary frequency.

作者信息

Sasaki Y, Hamada K, Yamazaki C, Seto T, Kimura Y, Ukai Y, Yoshikuni Y, Kimura K

机构信息

Research Laboratories, Nippon Shinyaku Co. Ltd., Minami-ku, Kyoto, Japan.

出版信息

Int J Urol. 1997 Jul;4(4):401-6. doi: 10.1111/j.1442-2042.1997.tb00215.x.

DOI:10.1111/j.1442-2042.1997.tb00215.x

PMID:9256331

Abstract

BACKGROUND

NS-21 is under development for the treatment of urinary frequency and urinary incontinence. The purpose of this study was to investigate the effects of NS-21 and its active metabolite, RCC-36, on lower urinary tract function in an experimental rat model of urinary frequency.

METHODS

Cystometrograms were recorded in anesthetized rats with bilaterally transected hypogastric nerves. All drugs were administered intraduodenally.

RESULTS

In sham-operated rats, NS-21 (> or = 50 mg/kg) significantly increased the bladder capacity without significantly decreasing micturition pressure, while RCC-36 (100 mg/kg) significantly increased bladder capacity, and at a dose of > or = 30 mg/kg, also caused a decrease in micturition pressure. This increase in bladder capacity appeared at lower doses of both NS-21 and RCC-36 in the hypogastric nerve-transected rats. Propiverine (100 mg/kg) increased bladder capacity and at > or = 30 mg/kg, decreased micturition pressure in both sham-operated and nerve-transected rats. Oxybutynin (100 mg/kg) and atropine (30 mg/kg) decreased the micturition pressure in both sham-operated and nerve-transected rats without increasing the bladder capacity, while a similar anticholinergic calcium antagonist, terodiline (100 mg/kg) had no effect on bladder capacity in either sham-operated or nerve-transected rats. Flavoxate (500 mg/kg) significantly increased bladder capacity without significantly decreasing micturition pressure in both sham-operated and nerve-transected rats, while 50 mg/kg of verapamil significantly increased bladder capacity without significantly decreasing the micturition pressure in nerve-transected rats.

CONCLUSIONS

NS-21 and RCC-36 increased bladder capacity at lower doses in hypogastric nerve-transected rats than in sham-operated rats. Furthermore, NS-21 increased the bladder capacity without suppressing micturition pressure, suggesting that NS-21 may be a more effective therapeutic drug than propiverine, oxybutynin or flavoxate for the treatment of urinary frequency and urinary incontinence.

摘要

背景

NS - 21正在研发用于治疗尿频和尿失禁。本研究的目的是在尿频的实验大鼠模型中研究NS - 21及其活性代谢产物RCC - 36对下尿路功能的影响。

方法

在双侧切断腹下神经的麻醉大鼠中记录膀胱内压图。所有药物均经十二指肠给药。

结果

在假手术大鼠中，NS - 21（≥50 mg/kg）显著增加膀胱容量，而不显著降低排尿压力，而RCC - 36（100 mg/kg）显著增加膀胱容量，且剂量≥30 mg/kg时，也会导致排尿压力降低。在腹下神经切断的大鼠中，NS - 21和RCC - 36在较低剂量时就出现膀胱容量增加。丙哌维林（100 mg/kg）增加膀胱容量，且在假手术和神经切断的大鼠中，剂量≥30 mg/kg时降低排尿压力。奥昔布宁（100 mg/kg）和阿托品（30 mg/kg）在假手术和神经切断的大鼠中均降低排尿压力，但不增加膀胱容量，而类似的抗胆碱能钙拮抗剂特罗地林（100 mg/kg）在假手术或神经切断的大鼠中对膀胱容量均无影响。黄酮哌酯（500 mg/kg）在假手术和神经切断大鼠中均显著增加膀胱容量，而不显著降低排尿压力，而50 mg/kg维拉帕米在神经切断大鼠中显著增加膀胱容量，而不显著降低排尿压力。