Selective beta-adrenoceptor agonists, calcium antagonists and potassium channel openers as a possible medical treatment of the overactive bladder and urge incontinence

Abstract

Urinary incontinence affects millions of people worldwide and also represents a social problem. People of all ages suffer from urinary incontinence. The disease is found in about 30% of women aged 30 to 60 years. There are different types of incontinence. Urge incontinence is the most often pharmacologically treated type. The mainly used substances belong to the class of antimuscarinic drugs. Their use is limited by several side effects. Furthermore, in some patients anticholinergic medication is ineffective and antimuscarinics used as single medication do not lead to a sufficient therapeutic effect. Other possible pharmacological substances for treatment of overactive bladder (detrusor instability) associated with urge and urge incontinence are the selective beta-adrenoceptor-agonists which are mainly responsible for the adrenergic mediated relaxation. It depends on the species, which beta-adrenoceptor-subtype (the beta2- and/or beta3-adrenoceptor) mainly mediates the relaxation. Non selective beta-adrenoceptor-agonists exhibit serious cardiovascular side effects like tachycardia or decrease of blood pressure by stimulating beta1- and beta2-adrenoceptors. These side effects should be decreased when using selective agonists. Additionally, substances whose targets are membrane channels of muscle cells could be interesting for treatment of overactive bladder. This group includes L-type calcium antagonists and potassium channel openers of ATP-sensitive potassium channels or BK channels. Especially the local use of the pharmacologically very potent calcium antagonists could be an interesting therapeutic approach, since systemic cardiovascular side effects were avoided. After chronic oral treatment with different calcium antagonists effects on the detrusor muscle were reduced or could not be detected, possibly due to an upregulation of 1,4-dihydropyridine-sensitive potassium channels. A very interesting approach is the use of potassium channel openers said to be selective for the urinary bladder. If there is a selectivity for the detrusor muscle, cardiovascular side effects were reduced. Possibly, the local use is a useful application form. Selective beta-adrenoceptor agonists, calcium antagonists and potassium channel openers are pharmacological approaches, which are not yet available for clinical use.