The in vivo
muscarinic receptor binding of
antimuscarinic agents (
oxybutynin,
solifenacin,
tolterodine, and
imidafenacin) used to treat urinary dysfunction in patients with
overactive bladder is reviewed.
Transdermal administration of
oxybutynin in rats leads to significant binding of
muscarinic receptors in the bladder without long-term binding in the submaxillary gland and the abolishment of salivation evoked by oral
oxybutynin. Oral
solifenacin shows significant and long-lasting binding to
muscarinic receptors in mouse tissues expressing the M(3) subtype. Oral
tolterodine binds more selectively to
muscarinic receptors in the bladder than in the submaxillary gland in mice. The
muscarinic receptor binding of oral
imidafenacin in rats is more selective and longer-lasting in the bladder than in other tissues such as the submaxillary gland, heart, colon, lung, and brain, suggesting preferential
muscarinic receptor binding in the bladder. In vivo quantitative autoradiography with (+)N-[(11)C]methyl-3-piperidyl benzilate in rats shows significant occupancy of brain
muscarinic receptors with the
intravenous injection of
oxybutynin,
solifenacin, and
tolterodine. The estimated in vivo selectivity in brain is significantly greater for
solifenacin and
tolterodine than for
oxybutynin.
Imidafenacin occupies few brain
muscarinic receptors. Similar findings for oral
oxybutynin were observed with positron emission tomography in conscious rhesus monkeys with a significant disturbance of short-term memory. The newer generation of
antimuscarinic agents may be advantageous in terms of bladder selectivity after systemic administration.