Treatment of overactive bladder: other drug mechanisms

The well-known side effects of antimuscarinic drugs have focused interest on other ways of treating overactive bladder. Targets for pharmacologic intervention may be found in the central nervous system (CNS) or peripherally. Several CNS transmitter systems can modulate voiding, but few drugs with a defined CNS site of action have been demonstrated to be clinically useful. The mechanism of action of imipramine, which may be effective in the treatment of overactive bladder, has not yet been clarified. Like imipramine, duloxetine is an inhibitor of serotonin (5-HT) and norepinephrine reuptake. Duloxetine has shown some promise in the treatment of urinary incontinence, but, as with the selective serotonin reuptake inhibitors, its effectiveness in the treatment of overactive bladder has not been proven. Drugs affecting norepinephrine, dopamine or gamma-aminobutyric acid (GABA) receptors and mechanisms may be useful. There is also evidence for a central site of action of alpha(1)-adrenoceptor (AR) antagonists. Traditionally, drugs for the treatment of overactive bladder have had a peripheral site of action. Drugs acting on ARs or membrane channels, as well as prostaglandin synthase inhibitors and several other agents, have been used with moderate success. However, recent developments may lead to more effective drugs, including potassium channel openers, prostaglandins, selective and nonselective inhibitors of cyclooxygenase and those acting on the beta(3)-ARs in the human detrusor. Drugs that reduce afferent activity represent an attractive therapeutic approach, and transmitters of afferent nerves and their receptors are possible targets for pharmacologic interventions.