Antimuscarinics and the overactive detrusor--which is the main mechanism of action?

Contraction of the bladder, voluntary or involuntary, involves stimulation of the muscarinic receptors on the detrusor by acetylcholine, released from activated cholinergic nerves. Antimuscarinics are the drugs of choice for treatment of detrusor overactivity and the overactive bladder (OAB) syndrome. However, antimuscarinics at clinically recommended doses have little effect on voiding contractions, and may act mainly during the bladder storage phase, during which there is normally no parasympathetic outflow from the spinal cord. Supporting this, antimuscarinics have been shown to reduce bladder tone during storage, and to increase cystometric bladder capacity. A basal release of acetylcholine from non-neuronal (urothelial) as well as neuronal sources has been demonstrated in isolated human detrusor muscle. It is suggested that this release, which is increased by stretching the muscle and in the aging bladder, contributes to detrusor overactivity and OAB by eventually increasing bladder afferent activity during storage.