Levin R M, Hayes L, Zhao Y, Wein A J
Division of Urology, University of Pennsylvania School of Medicine, Philadelphia Veterans Administration Medical Center.
Pharmacology. 1992;45(1):1-8. doi: 10.1159/000138966.
Uninhibited bladder contractions have been associated with a variety of bladder dysfunctions including outlet obstruction, neurogenic bladder, incontinence, and other neurologic and nonneurogenic bladder disorders. One class of compounds that is gaining popularity and support for the treatment of hyperreflexia is potassium channel openers, such as pinacidil and cromakalim. In general, these agents act by hyperpolarizing the smooth muscle membrane, resulting in an increase in membrane stability which in turn would be expected to inhibit spontaneous and evoked contraction. It is the purpose of this study to compare the potency and selectivity of pinacidil at inhibiting both hyperreflexia in vivo, and several forms of in vitro contractile stimulation in the rabbit. The following is a summary of the results. (1) Pinacidil is an effective inhibitor of hyperreflexia in the in vivo rabbit model. (2) Pinacidil is a substantially more potent inhibitor of the amplitude of the hyperreflexia than the frequency. (3) Pinacidil was substantially more potent at inhibiting the contractile response to 2-Hz stimulation than to 32-Hz stimulation, but was equally effective at inhibiting field stimulation of the bladder base and body. (4) Pinacidil was significantly more potent at inhibiting the peak response to field stimulation than the rate of tension generation. (5) Pinacidil was equally potent and effective at inhibiting the phasic and tonic components of the response to field stimulation. (6) Pinacidil was a more potent inhibitor of methoxamine stimulation of the bladder base than bethanechol stimulation of the bladder body. (7) Pinacidil was a noncompetitive or mixed inhibitor of both methoxamine and bethanechol stimulation, whereas it was a competitive inhibitor of KCl stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)
无抑制性膀胱收缩与多种膀胱功能障碍有关，包括出口梗阻、神经源性膀胱、尿失禁以及其他神经和非神经源性膀胱疾病。一类在治疗膀胱反射亢进方面越来越受到关注和支持的化合物是钾通道开放剂，如吡那地尔和克罗卡林。一般来说，这些药物通过使平滑肌膜超极化起作用，导致膜稳定性增加，进而预期会抑制自发和诱发的收缩。本研究的目的是比较吡那地尔在抑制兔体内反射亢进和几种体外收缩刺激形式方面的效力和选择性。以下是结果总结。（1）吡那地尔是兔体内反射亢进的有效抑制剂。（2）吡那地尔对反射亢进幅度的抑制作用比频率更强。（3）吡那地尔对2赫兹刺激的收缩反应的抑制作用比对32赫兹刺激更强，但对膀胱底部和体部的场刺激抑制效果相同。（4）吡那地尔对场刺激峰值反应的抑制作用比对张力产生速率的抑制作用显著更强。（5）吡那地尔对场刺激反应的相位和张力成分的抑制作用效力和效果相同。（6）吡那地尔对膀胱底部甲氧明刺激的抑制作用比对膀胱体部氨甲酰甲胆碱刺激更强。（7）吡那地尔对甲氧明和氨甲酰甲胆碱刺激均为非竞争性或混合性抑制剂，而对氯化钾刺激为竞争性抑制剂。（摘要截取自250词）
