D'Aquila Paolo S, Panin Francesca, Cossu Maria, Peana Alessandra T, Serra Gino
Dipartimento di Scienze del Farmaco, Università di Sassari, Via Muroni 23/A, 07100 Sassari, Italy.
Eur J Pharmacol. 2003 Jan 26;460(1):71-4. doi: 10.1016/s0014-2999(02)02881-9.
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-hydroxy-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.
多巴胺受体激动剂阿扑吗啡最近已被用于治疗勃起功能障碍。虽然多巴胺D2样受体在这一作用中起关键作用已得到充分证实，但关于多巴胺D1样受体的作用，文献报道的结果相互矛盾。本研究的目的是确定全身给予多巴胺D1样受体激动剂对大鼠阴茎勃起的影响。雄性Wistar大鼠接受三种不同且结构不相关的多巴胺D1样受体激动剂治疗：部分激动剂SKF38393（(+) 2,3,4,5-四氢-7,8-二羟基-1-苯基-1H-3-苯并氮杂卓）和CY 208-243（(-)-4,6,6a,7,8,12b-六氢-7-甲基吲哚[4,3-ab]菲啶），以及完全激动剂A 77636（(-)-(1R,3S)-3-金刚烷基-1-(氨甲基)-3,4-二氢-5,6-二羟基-1H-2-苯并吡喃盐酸盐）。所有三种化合物均剂量依赖性地增加阴茎勃起次数，完全激动剂A77636相对于其他两种化合物显示出更明显的效果。此外，多巴胺D1样受体拮抗剂SCH 23390（(R)-(+)-7-氯-8-羟基-3-甲基-1-苯基-2,3,4,5-四氢-1H-3-苯并氮杂卓）剂量依赖性地拮抗A77636的作用。这些结果表明，全身给予多巴胺D1样受体激动剂可诱导大鼠阴茎勃起。这一观察结果表明，多巴胺D1样受体激动剂在治疗勃起功能障碍时可能被视为阿扑吗啡的一种可能替代物，从而避免与刺激多巴胺D2样受体相关的典型副作用，如恶心。
