L. Sorbera, J. Castaǹer
2004
Citations
0
Influential Citations
3
Citations
Journal
Drugs of The Future
Abstract
Stress urinary incontinence is the most common form of urinary incontinence. Adrenergic receptors have been the focus of research to develop effective agents to manage the disorder. The α 1 A -adrenoceptor subtype in particular is found in abundance in the bladder neck and proximal urethra and is recognized as playing an important role in the sympathetic neuronal control of urinary outlet tissue smooth muscle tone. However, selective α 1 A -adrenoceptor agonists which have been shown to be effective in relieving symptoms of urinary incontinence are associated with unwanted hemodynamic effects such as elevation of blood pressure. The α 1 L -adrenoceptor is a fourth adrenoceptor subtype identified and found to mediate contraction of urinary outlet smooth muscle. Evidence suggests that this subtype is actually a pharmacological form of the α 1 A -adrenoceptor gene product. The α 1 A - and α 1 L -adrenoceptors together have therefore become attractive targets for the development of agents with improved safety profiles for the treatment of stress urinary incontinence. Dabuzalgron (Ro-115-1240, R-450) is a novel α 1 A / 1 L -adrenoceptor partial agonist that has been shown to control urethral smooth muscle in vitro and in vivo. Moreover, the agent emerged as safe and effective as a treatment for stress urinary incontinence from a randomized trial.