Molecular and Cellular Pharmacology, Vol 3, No 2 (2011)

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Bladder Selectivity of Imidafenacin, a Novel Antimuscarinic Agent Developed to Treat Overactive Bladder

Shizuo Yamada, Akira Yoshida, Masaki Ogoda, Yusuke Fuchihata, Shiori Kuraoka, Hideo Tsukada, Tsuyoshi Anraku


Imidafenacin, a potent M1 and M3-subtype selective antagonist, is now used clinically in Japan for the treatment of overactive bladder (OAB). Pharmacological studies of this agent showed selectivity in the bladder over salivary gland and brain. The oral administration of imidafenacin at low doses caused a more selective and longer-lasting binding to muscarinic receptors in the bladder than at other tissues such as the salivary gland, heart, colon, lung and brain, suggesting preferential muscarinic receptor binding in the bladder. Pharmacokinetic data showed that the orally administered imidafenacin distributed at a higher concentration in the bladder compared to that in the serum or submaxillary gland of rats. Furthermore, a significant level of imidafenacin was detected in the urine of rats treated orally with this agent. The intravesical instillation of imidafenacin resulted in significant binding of bladder muscarinic receptors. In experiments using autoradiography (ARG) and positron emission tomography (PET), imidafenacin exerted little significant binding of muscarinic receptors in rat brain and no impairment of cognitive behavior in rats and monkeys. Clinical studies indicated a favorable efficacy-to-side effect ratio of imidafenacin in patients with OAB. Thus, imidafenacin when given orally exhibits predominant distribution to the bladder and possibly exerting a more selective and persistent pharmacological effect on the bladder than other tissues including the submaxillary gland, colon and brain. Such selectivity may be attributable to a direct blockade of bladder muscarinic receptors by the excreted urinary imidafenacin. Thus, imidafenacin may be efficacious in treating patients with an overactive bladder, with the improved tolerability beyond the currently available agents.

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