Advances in the Treatment of Erectile Dysfunction

US Endocrinology, 2006;(2): DOI:


Progress in the clinical management of erectile disorders, and specifically erectile dysfunction (ED), has gained substantially from basic science advances in the field. Unquestionably, the advance of phosphodiesterase 5 (PDE5) inhibitor therapy quickly followed the basic scientific description of nitric oxide (NO) signaling in erectile tissue. Further investigation of the neurotransmission involved in penile erection, hormone actions involved in this response, and biochemical signal transduction processes within the erectile tissue represent major areas of scientific pursuit. Current objectives scientifically are to identify and characterize molecular targets operating at multiple levels of the nervous system, endocrine system, and vascular system all related to penile erection. It is conceivable that new knowledge involving these systems may be exploited to develop various therapeutic approaches to manage ED. These approaches include pharmacotherapy, growth factor interventions, cell and tissue engineering, and gene therapy.

Central Nervous System Targets
At the level of the central nervous system (CNS), neurotransmitters and their receptors and neuronal pathways represent molecular targets that may be exploited for the purpose of treating ED. Prominent among these are the chemicals dopamine, melanocortin, oxytocin, hexarelin analogue, serotonin, noradrenaline, and NO. The dopaminergic system has already been approached at the clinical level with the development and use of apomorphine, a dopamine receptor agonist. Regulatory approval for the human use of this medication has been achieved in countries outside of the US. However, because of nausea and syncope, the medication has not been approved for clinical distribution in the US. Nonetheless, preclinical studies have continued to show that the dopaminergic system may be fruitful for clinical applications, and further studies of this sort may lead to the development of dopamine-selective agonists operating at specific receptor subtypes in the human brain that exert optimal clinical efficacy without adverse effects.

An additional system that has gained great interest for its potential in the treatment of ED is the melanocortinergic system. Early phase clinical trials have demonstrated that PT-141, a cyclic heptapeptide melanocortin analogue, elicits erectile responses in both healthy men and men with mild-to-moderate ED. These trials have demonstrated responses in men who were non-responsive to PDE5 inhibitor therapy. The medication can be administered by either intranasal or subcutaneous routes. Study participants have tolerated the medication only reporting occasional flushing and nausea. At this time, regulatory agency approval of this medication has not yet been achieved. Further studies are necessary to develop and evaluate drugs contended to have utility via other select neuronal systems at the CNS level.