The overactive bladder: pharmacologic basis of drug treatment

To provide an overview of the basis for drug treatment of the overactive bladder.

Published information is evaluated.

The causes of bladder overactivity are not known, but theoretically, increased afferent activity, decreased inhibitory control in the central nervous system (CNS) or peripheral ganglia, and increased sensitivity of the detrusor to efferent stimulation may be involved. Several CNS transmitters can modulate voiding, but few useful drugs with a defined CNS site of action have been developed. Drugs that stimulate gamma-aminobutyric acid receptors are used clinically. Potentially, drugs affecting opioid, 5-hydroxytryptamine, norepinephrine, dopamine, and glutamatergic receptors and mechanisms can be developed, but a selective action on the lower urinary tract may be difficult to obtain. Traditionally, drugs used for treatment of bladder overactivity have had a peripheral site of action, mainly efferent neurotransmission or the detrusor itself. Antimuscarinic drugs, beta-adrenoceptor agonists, alpha-adrenoceptor antagonists, drugs affecting membrane channels, prostaglandin synthetase inhibitors, and several other agents have been used with limited success. New information on the alpha-adrenoceptor and muscarinic receptor subtypes in the human detrusor has emerged and may be the basis for the development of new compounds with effects on bladder overactivity. Decreasing afferent activity seems an attractive therapeutic approach, and drugs affecting afferent nerves by causing release of tachykinins, such as capsaicin and analogs, as well as agents blocking tachykinin receptors, may be of therapeutic interest.

New drugs, specifically designed for the treatment of bladder overactivity, are desirable.