Hertle L, Nawrath H
Urol Int. 1984;39(2):84-90. doi: 10.1159/000280951.
The effects of the constituents of Baralgin ( metamizole , fenpiverinium , and pitofenone ) on mechanical activity were studied in isolated human preparations of the upper urinary tract. Metamizole in concentrations up to 10(-3) mol/l did influence neither spontaneous phasic activity nor activation by high external potassium, norepinephrine, or acetylcholine. Fenpiverinium blocked the increase in frequency of phasic-rhythmic contractions and the tonic tension development induced by acetylcholine. Fenpiverinium did influence neither spontaneous phasic activity nor activation by high potassium or norepinephrine. Pitofenone (10(-3)mol/l) antagonized completely spontaneous phasic-rhythmic as well as norepinephrine- or acetylcholine-induced phasic activity. The tonic activation induced by norepinephrine and acetylcholine was nearly completely inhibited. Pitofenone (10(-6) to 10(-3) mol/l) antagonized the high potassium-induced activation in a concentration-dependent way. The EC50 of pitofenone amounted to 2 X 10(-4) mol/l. Uptake measurements of 14C- pitofenone (2 X 10(-4) mol/l) in isolated ureteral segments showed the drug to be accumulated in the ureteral tissue; a tissue/medium ratio of about 3 was found at an exposure time of 60 min. The accumulation of the drug was reversible after washing in drug-free solution, indicated by the loss of radioactivity increasing with longer washing times. The results show that pitofenone has a direct relaxant effect on smooth muscle of the upper urinary tract, whereas fenpiverinium has exclusively anticholinergic properties. Metamizole had no direct effect on smooth muscle activity, and its clinical effects may be rather due to its analgesic action.
在离体的人体上泌尿道制剂中研究了巴拉丁（安乃近、芬维铵和匹托非诺）成分对机械活动的影响。浓度高达10⁻³mol/L的安乃近既不影响自发性节律性活动，也不影响高钾、去甲肾上腺素或乙酰胆碱引起的激活作用。芬维铵可阻断乙酰胆碱诱导的节律性收缩频率增加和张力发展。芬维铵既不影响自发性节律性活动，也不影响高钾或去甲肾上腺素引起的激活作用。匹托非诺（10⁻³mol/L）完全拮抗自发性节律性活动以及去甲肾上腺素或乙酰胆碱诱导的节律性活动。去甲肾上腺素和乙酰胆碱诱导的张力性激活几乎被完全抑制。匹托非诺（10⁻⁶至10⁻³mol/L）以浓度依赖的方式拮抗高钾诱导的激活作用。匹托非诺的半数有效浓度（EC50）为2×10⁻⁴mol/L。在离体输尿管段中对¹⁴C-匹托非诺（2×10⁻⁴mol/L）的摄取测量表明，该药物在输尿管组织中蓄积；在暴露60分钟时，组织/培养基比值约为3。在无药物溶液中冲洗后，药物的蓄积是可逆的，放射性损失随冲洗时间延长而增加表明了这一点。结果表明，匹托非诺对上泌尿道平滑肌有直接舒张作用，而芬维铵仅具有抗胆碱能特性。安乃近对平滑肌活动无直接影响，其临床效果可能主要归因于其镇痛作用。
