Urinary incontinence - dabuzalgron
Of the various types of urinary incontinence, stress incontinence is much the most common. It represents an involuntary leakage of urine on sneezing, coughing or exertion, and as many as half of all adult women are thought to be affected to some degree. It often results from a weakening by pregnancy and childbirth in the muscles in the pelvic floor that support the bladder, although obesity, constipation, lung disease and smoking may also be factors.
Various drug treatments are already available. In particular, the adrenergic receptors are a target for therapy, as the b3-adrenoceptor controls detrusor relaxation without affecting the cardiovascular system. There are also numerous different a-adrenoceptors in the neck of the bladder and the urethra. Both the a1A and a1L subtype are attractive targets for pharmacological intervention. The former is implicated in the sympathetic neural control of urinary outlet tissue smooth muscle tone, and the latter mediates contraction of smooth muscle in the urinary outlet.
Selective a1 adrenoceptor agonists like midodrine relieve symptoms effectively, but cause dose-dependent haemodynamic effects such as raised blood pressure. A new molecule, which acts selectively at both the 1A and 1L receptor subtypes, is dabuzalgron, being co-developed by Chugai Pharmaceutical and Roche. It has minimal haemodynamic effects.1
A multi-centre randomised placebo-controlled crossover study has been carried out in 37 women with mild to moderate stress urinary incontinence.2 Subjects were given 1.5mg of dabuzalgron twice a day for two or four weeks, and the drug was well tolerated. The commonest side-effects were headache, paraesthesia and pruritis. No significant changes in blood pressure were observed. The subjects given the active had significantly fewer incidences of stress urinary incontinence than those who had taken placebo. Further studies are under way.