Oral α adrenoceptor blockade as a treatment of erectile dysfunction

Abstract

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.

Multidimensional nature of apomorphine SL (IxenseTM) therapy

“…5 It has been demonstrated that intracavernous injection of a-adrenergic agonists results in maximum contraction 8 while antagonists produce erections. 9 Similar results have been demonstrated ex vivo using isolated smooth muscle cells from human penile corpus cavernosum. 10 The role of NA is not limited to the peripheral nervous system.…”

The Old Made New: Natural Compounds against Erectile Dysfunction

“…As an example, alprostadil acts as a PGE1 agonist and affects the adenylate cyclase (AC)-cAMP pathway [28,29]. Besides this, inhibition of the vasoconstriction is another possible strategy that could be pursued opportunely interacting with endothelin [30], angiotensin [31], and adrenergic receptors [32].…”

Interactions between drugs for erectile dysfunction and drugs for cardiovascular disease

“…81 In patients with erectile insufficiency oral or buccal phentolamine has shown some success. 82,83 Phentolamine also blocks a 1 and a 2 -adrenoceptors in the systemic arterial circulation and therefore, hypotension is the major adverse effect of phentolamine. The hypotensive action of phentolamine is followed by compensatory reflex cardiac stimulation by tachycardia, and the latter response is blunted in patients treated with badrenoceptor antagonists.…”