Effects of 3-methyl-4-oxo-2-phenyl-N-(2-(1-piperidinyl)ethyl)-4H-1-benzopyran-8-carboxamide hydrochloride monohydrate (FL-155), a new anti-pollakiuria agent, on the rhythmic bladder contractions in anesthetized rats.

Abstract

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 .apprx. 3.0 mg/kg and 1.0 .apprx. 3.0 mg/kg, respectively) and intraduodenal (12.5 .apprx. 100 mg/kg and 200 .apprx. 400 mg/kg, respectively) administration, dose-dependently abolished the rhythmic bladder contractions, and FL-155 was 8.apprx. 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.