Kikukawa H, Yoshida M, Wada Y, Nishi K, Ueda S
Department of Urology, Kumamoto University School of Medicine, Japan.
Int J Urol. 1998 May;5(3):268-75. doi: 10.1111/j.1442-2042.1998.tb00602.x.
Temiverine (p-INN) is a newly synthesized drug that is expected to have anticholinergic action. We investigated the pharmacologic actions of temiverine and its active metabolite, RCC-36, on isolated human bladder.
Effects of temiverine and RCC-36 on the detrusor contractions induced by acetylcholine, potassium chloride (KCl), calcium chloride (CaCl2), and electric field stimulation were evaluated using the muscle-bath technique, and compared with the effects of atropine and oxybutynin.
Atropine (10(-9) to 10(-6) mol/L), oxybutynin (10(-8) to 10(-5) mol/L), temiverine (10(-8) to 10(-5) mol/L), and RCC-36 (10(-8) to 3 x 10(-6) mol/L) caused a parallel shift to the right of the concentration-response curves to acetylcholine stimulation. The rank order of pA2 value was atropine > oxybutynin = RCC-36 > temiverine. Atropine did not suppress the maximum contractile response to acetylcholine, but the other drugs significantly suppressed this at the higher concentrations. Each drug caused a concentration-dependent inhibition of KCl (80 mmol/L)-, and CaCl2 (5 mmol/L)-induced contractile responses. Rank order of maximum inhibition was RCC-36 = temiverine > oxybutynin > atropine. Each drug caused a concentration-dependent inhibition of electric field-induced contraction with or without 10(-6) mol/L atropine pretreatment. Maximum inhibitions of temiverine and RCC-36 were significantly greater than that of oxybutynin.
Atropine, oxybutynin, temiverine, and RCC-36 have different efficacies and potencies of anticholinergic and calcium antagonistic activity on isolated human detrusor muscles. Furthermore, temiverine and RCC-36 have significant inhibitory actions toward the atropine-resistant part of contractions, which may be related to the calcium antagonistic actions of these compounds.
替米维林（p-INN）是一种新合成的有望具有抗胆碱能作用的药物。我们研究了替米维林及其活性代谢产物RCC-36对离体人膀胱的药理作用。
采用肌肉浴技术评估替米维林和RCC-36对乙酰胆碱、氯化钾（KCl）、氯化钙（CaCl2）和电场刺激诱导的逼尿肌收缩的影响，并与阿托品和奥昔布宁的作用进行比较。
阿托品（10^(-9)至10^(-6)mol/L）、奥昔布宁（10^(-8)至10^(-5)mol/L）、替米维林（10^(-8)至10^(-5)mol/L）和RCC-36（10^(-8)至3×10^(-6)mol/L）使乙酰胆碱刺激的浓度-反应曲线平行右移。pA2值的顺序为阿托品＞奥昔布宁 = RCC-36＞替米维林。阿托品不抑制对乙酰胆碱的最大收缩反应，但其他药物在较高浓度时可显著抑制。每种药物均引起对KCl（80mmol/L）和CaCl2（5mmol/L）诱导的收缩反应的浓度依赖性抑制。最大抑制顺序为RCC-36 = 替米维林＞奥昔布宁＞阿托品。每种药物均引起对电场诱导收缩的浓度依赖性抑制，无论是否进行10^(-6)mol/L阿托品预处理。替米维林和RCC-36的最大抑制作用明显大于奥昔布宁。
阿托品、奥昔布宁、替米维林和RCC-36对离体人逼尿肌具有不同的抗胆碱能和钙拮抗活性效力和效能。此外，替米维林和RCC-36对阿托品抵抗性收缩部分具有显著抑制作用，这可能与这些化合物的钙拮抗作用有关。
