Morikawa K, Yamauchi T, Kato H, Ito Y
Nihon Yakurigaku Zasshi. 1986 Nov;88(5):355-61. doi: 10.1254/fpj.88.355.
The effects of FL-155, which was synthesized to develop a new orally-active anti-pollakiuria agent, on the rhythmic bladder contractions were studied in anesthetized rats. At a pressure exceeding 10 cm H2O in the bladder, a rhythmic bladder contraction was observed up to at least 120 min. This response was abolished by a spinal (C1 level) cut, cuts of both pelvic nerves, thiopental (3.0 mg/kg, i.v.) or lidocaine (1.0 mg/kg, i.v.); and atropine (0.01 mg/kg, i.v.) strongly inhibited the amplitude of the response. FL-155 and flavoxate, in intravenous (0.3-3.0 mg/kg and 1.0-3.0 mg/kg, respectively) and intraduodenal (12.5-100 mg/kg and 200-400 mg/kg, respectively) administrations, dose-dependently abolished the rhythmic bladder contractions, and FL-155 was 8-16 times more potent than flavoxate in intraduodenal administrations. These results suggest that the rhythmic bladder contraction in anesthetized rat may be a polysynaptic reflex through pelvic nerves and the central nervous system (supraspinal level), and FL-155 appears to be a candidate for an orally active anti-pollakiuria agent.
为研发一种新型口服活性抗尿频药物而合成的FL - 155,对麻醉大鼠膀胱节律性收缩的影响进行了研究。当膀胱内压力超过10 cm H₂O时,观察到膀胱节律性收缩至少持续120分钟。这种反应可通过脊髓(C1水平)横断、双侧盆神经切断、硫喷妥钠(3.0 mg/kg,静脉注射)或利多卡因(1.0 mg/kg,静脉注射)消除;阿托品(0.01 mg/kg,静脉注射)强烈抑制反应幅度。静脉注射(分别为0.3 - 3.0 mg/kg和1.0 - 3.0 mg/kg)和十二指肠内给药(分别为12.5 - 100 mg/kg和200 - 400 mg/kg)时,FL - 155和黄酮哌酯剂量依赖性地消除膀胱节律性收缩,在十二指肠内给药时,FL - 155的效力比黄酮哌酯强8 - 16倍。这些结果表明,麻醉大鼠的膀胱节律性收缩可能是通过盆神经和中枢神经系统(脊髓以上水平)的多突触反射,并且FL - 155似乎是一种口服活性抗尿频药物的候选物。