Modulation of Dopaminergic Pathways to Treat Erectile Dysfunction.

Article Details

Citation

Copy to clipboard

Simonsen U, Comerma-Steffensen S, Andersson KE

Modulation of Dopaminergic Pathways to Treat Erectile Dysfunction.

Basic Clin Pharmacol Toxicol. 2016 Oct;119 Suppl 3:63-74. doi: 10.1111/bcpt.12653.

PubMed ID

27541930 [ View in PubMed

]

Abstract

The currently recommended first-line treatments of erectile dysfunction (ED), phosphodiesterase type 5 inhibitors (PDE5i), for example sildenafil, are efficacious in many patients with ED of vascular origin, but this therapy is insufficient in approximately 30-40% of men with ED where there is also a neuronal affection. There is a demand of novel approaches to treat the condition. We review the possibility of modulating the dopaminergic pathways to improve erectile function. Dopamine D1 (D1 , D5 )- and D2 (D2 -D4 )-like receptors in the paraventricular area, the medial pre-optic area, the spinal cord, and in the erectile tissue are involved in erection, and several agonists developed for the treatment of Parkinson's disease are associated with increased libido. A therapeutic window for the treatment of ED was found by sublingual administration of the general dopamine receptor agonist apomorphine, but it failed mainly due to less efficacy on erectile function compared with PDE5i. To avoid the dose-limiting side effects mediated by D2 receptors, nausea and emesis, dopamine D4 receptor agonists were developed, and they induce erection in rodents, but these drugs were never introduced clinically. The beta-lactamase inhibitor clavulanic acid increases dopamine and serotonin and was found to increase sexual arousal and erections, but the dose-response curve is bell-shaped. Bupropion has selectivity for inhibition of the dopamine reuptake transporter and can be used to alleviate sexual symptoms caused by other antidepressant medication, hence providing an interesting approach to treat ED. In summary, modulation of the dopaminergic pathways provides a possibility to improve the treatment of ED.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Bupropion	Sodium-dependent dopamine transporter	Protein	Humans	Yes	Inhibitor	Details