Dopamine D1 receptor agonists induce penile erections in rats

The dopamine receptor agonist apomorphine has been recently introduced in the treatment of erectile dysfunction. While it is well established that dopamine D2-like receptors play a crucial role in this effect, conflicting result are reported in the literature as for the role of dopamine D1-like receptors. The aim of this study was to determine the effect of systemic administration of dopamine D1-like receptor agonists on penile erection in rats. Male Wistar rats were treated with three different, and not structurally related, dopamine D1-like receptor agonists: the partial agonists SKF38393 ((+) 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine) and CY 208-243 ((-)-4,6,6a,7,8,12b-exahydro-7-methylindole [4,3-ab]fenantridine), and the full agonist A 77636 ((-)-(1R,3S)-3-Adamantyl-1-(aminomethyl)-3,4-dihydro-5,6-dihydroxy-1H-2- benzopyran hydrochloride). All three compounds dose-dependently increased the number of penile erections, with the full agonist A77636 showing a more pronounced effect with respect to the other two. Moreover, the dopamine D1-like receptor antagonist SCH 23390 ((R)-(+)-7-chloro-8-hydorxy-3-methyl-1-phenyl-2,3,4,5-tetrahydro-1H-3- benzazepine) dose-dependently antagonised A77636 effect. These results show that systemic administration of dopamine D1-like receptor agonists induce penile erection in rats. This observation suggests that dopamine D1-like receptor agonists might be considered as a possible alternative to apomorphine in the treatment of erectile dysfunction, thus avoiding the typical side effects related to the stimulation of dopamine D2-like receptors such as nausea.