Oral α adrenoceptor blockade as a treatment of erectile dysfunction

The sympathetic nervous system, via release of noradrenaline (NA) and stimulation of α adrenoceptors (ARs), is considered to be the prime determinant of cavernosal smooth muscle contraction and detumescence. A relative predominance of NA-induced contraction over nitric oxide-mediated relaxation may contribute to erectile dysfunction (ED). Therefore α AR antagonism seems an attractive way of treating ED, but so far the therapeutic success of oral treatment has been limited. Modest activity has been documented for the α2 AR antagonist, yohimbine, which is believed to act in the central nervous system. Phentolamine, mainly blocking α1 and α2 ARs peripherally, has been shown to have beneficial effects, but the efficacy compared to other alternatives, e.g., sildenafil, has not been established. To improve oral treatment of ED with α AR antagonists, new drugs are required. However, little is known about central noradrenergic mechanisms involved in erection, or which α AR subtypes in the penile erectile tissues are the most important for mediation of contraction. It is still unclear what profile (α1 vs α2 ARs; selectivity for α1 and/or α2 AR subtypes) is the most advantageous for an α AR antagonist in the treatment of ED.