Control of penile erection by the melanocortinergic system: experimental evidences and therapeutic perspectives.

Penile erection is the ultimate vasculo-tissular response to an integrated and complex series of physiological processes elicited by psychological, neural, and hemodynamic events (Giuliano and Rampin, 2000; Saenz de Tejada, 2002). Upon sexual stimulation, penile erection, occurring in response to the activation of proerectile autonomic pathways, is greatly dependent on adequate inflow of blood to the erectile tissue and requires coordinated arterial endothelium-dependent vasodilatation and sinusoidal endothelium-dependent corporal smooth muscle relaxation. Most of the research efforts toward the treatment of erectile dysfunction (ED) have targeted the peripheral mechanisms of penile erection. These efforts have led to the identification of several compounds that can induce smooth muscle relaxation and erection by acting on cellular receptors (eg, prostaglandin E1) (Hedlund and Andersson, 1985; Stackl et al, 1988) or the intracellular machinery involved in the transduction of the signal (eg, sildenafil and other phosphodiesterase 5 inhibitors) (Giuliano, 2002). The registration in several countries of apomorphine for the treatment of ED has demonstrated the possibility of enhancing penile erection by acting elsewhere than on corpus cavernosum smooth muscle cells (Giuliano and Allard, 2002). The central nervous system (CNS) and, more specifically, the structures and neurotransmitters involved in the control of penile erection, represent, at least theoretically, a valuable alternative target for overcoming ED. In the CNS, several effectors involved in the control of erectile function have been identified. These include primarily dopamine, serotonin, noradrenaline, excitatory amino acids,