Which muscarinic receptor is important in the bladder?

Antimuscarinic agents are the most widely used therapy for urge incontinenc e, but have side effects such as constipation, tachycardia and dry mouth, r esulting from a lack of selectivity for the bladder. M-2 receptors are the predominant cholinoceptors present in urinary bladder, but mainly the minor population of M-3 receptors mediate its contraction. M-2 receptors modulat e detrusor contraction by several mechanisms, and may contribute more to co ntraction of the bladder in pathological states such as bladder denervation or spinal cord injury. Prejunctional inhibitory M-2 or M-4 receptors and p rejunctional facilitatory muscarinic M-1 receptors in the bladder have all been reported. In clinical studies, tolterodine, a non-selective muscarinic antagonist, has been reported to be as effective as oxybutynin but inducin g less dry mouth. Thus, although it is not certain which antimuscarinic dru gs have the better efficacy and tolerability, the non-selective antimuscari nic drugs seem to be better than M-3-selective antagonists in their clinica l efficacies. However, controlled release, or intravesical, intravaginal, o r rectal administrations of oxybutynin have been reported to cause fewer si de effects. Darifenacin, a new M-3 selective antagonist, has been reported to have selectivity for the bladder over the salivary gland in vivo. To ver ify which antimuscarinic drugs selective for the muscarinic subtypes have t he best efficacy and tolerability, comparative clinical trials between M-3 selective antagonists and non-selective compounds, such as olterodine, are required in the future.