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.