The Bifunctional μ Opioid Agonist/Antioxidant Dmt1DALDA Is a Superior Analgesic in an Animal Model of Complex Regional Pain Syndrome-Type I

摘要

Reactive oxygen species (ROS) play an important role in the development of complex regional pain syndrome-Type I (CRPS-I), as also demonstrated with the chronic post ischemia pain (CPIP) animal model of CRPS-I. We show that morphine and the antioxidant N-acetylcysteine (NAC) act synergistically to reduce mechanical allodynia in CPIP rats. The tetrapeptide amide [Dmt¹]DALDA (H-Dmt-d-Arg-Phe-Lys-NH2) is a potent and selective μ opioid receptor (MOR) agonist with favorable pharmacokinetic properties and with antioxidant activity due to its N-terminal Dmt (2′,6′-dimethyltyrosine) residue. In the CPIP model, [Dmt¹]DALDA was 15-fold more potent than morphine in reversing mechanical allodynia and 4.5-fold more potent as analgesic in the heat algesia test. The results indicate that bifunctional compounds with MOR agonist/antioxidant activity have therapeutic potential for the treatment of CRPS-I.