Antimuscarinics suppress adenosine triphosphate and prostaglandin E2 release from urothelium with potential improvement in detrusor overactivity in rats with cerebral infarction.

Abstract

Antimuscarinics improve detrusor overactivity. We evaluated the effects and action mechanisms of imidafenacin (Kyorin Pharmaceutical, Tokyo, Japan), a novel therapeutic agent for overactive bladder with antimuscarinic activity, on mediator release from urothelium and detrusor overactivity induced by cerebral infarction.
Bladder hydrodistention was achieved by intravesical infusion of Krebs solution. Bladder adenosine triphosphate and prostaglandin E(2) were measured in the presence and absence of anticholinergics using luciferin-luciferase assay and enzyme-linked immunoassay, respectively. Cerebral infarction was induced in rats by occluding the left middle cerebral artery. The effects of intravenous imidafenacin on bladder function were examined using cystometry in rats with cerebral infarction and in those pretreated with resiniferatoxin.
Increased intravesical adenosine triphosphate and prostaglandin E(2) were shown by induced distention of isolated rat bladders. Imidafenacin and darifenacin (Kemprotec, Middlesbrough, United Kingdom) significantly suppressed the increases in adenosine triphosphate and prostaglandin E(2). Decreased bladder capacity was observed in rats with cerebral infarction. Detrusor overactivity was suppressed with a minimum intravenous dose of 0.001 mg/kg imidafenacin. The effects of imidafenacin were not noted in rats pretreated with resiniferatoxin.
Results support the hypothesis or suggest that imidafenacin improves cerebral infarction induced detrusor overactivity by suppressing peripheral C-fibers. This effect is thought to be associated with suppression of the release of adenosine triphosphate and prostaglandin E(2) from the urothelium.