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Oral alpha adrenoceptor blockade as a treatment of erectile dysfunction.

The sympathetic nervous system, via release of noradrenaline (NA) and stimulation of alpha 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 alpha 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 alpha2 AR antagonist, yohimbine, which is believed to act in the central nervous system. Phentolamine, mainly blocking alpha1 and alpha2 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 alpha AR antagonists, new drugs are required. However, little is known about central noradrenergic mechanisms involved in erection, or which alpha AR subtypes in the penile erectile tissues are the most important for mediation of contraction. It is still unclear what profile (alpha1 vs alpha2 ARs; selectivity for alpha1 and/or alpha2 AR subtypes) is the most advantageous for an alpha AR antagonist in the treatment of ED.