Antimuscarinic agents are the most widely used
therapy for
urge incontinence, but have side effects such as
constipation,
tachycardia and dry mouth, resulting from a lack of selectivity for the bladder. M2 receptors are the predominant
cholinoceptors present in urinary bladder, but mainly the minor population of M3 receptors mediate its contraction. M2 receptors modulate detrusor contraction by several mechanisms, and may contribute more to contraction of the bladder in pathological states such as bladder
denervation or
spinal cord injury. Prejunctional inhibitory M2 or M4 receptors and prejunctional facilitatory
muscarinic Ml 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 inducing less dry mouth. Thus, although it is not certain which
antimuscarinic drugs have the better efficacy and tolerability, the non-selective
antimuscarinic drugs seem to be better than M3-selective antagonists in their clinical efficacies. However, controlled release, or intravesical, intravaginal, or
rectal administrations of
oxybutynin have been reported to cause fewer side effects.
Darifenacin, a new M3 selective antagonist, has been reported to have selectivity for the bladder over the salivary gland in vivo. To verify which
antimuscarinic drugs selective for the
muscarinic subtypes have the best efficacy and tolerability, comparative clinical trials between M3 selective antagonists and non-selective compounds, such as olterodine, are required in the future.