The bifunctional μ opioid agonist/antioxidant [Dmt(1)]DALDA is a superior analgesic in an animal model of complex regional pain syndrome-type i.

Abstract

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 [Dmt(1)]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, [Dmt(1)]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.

• Authors: Peter W Schiller, Thi M-D Nguyen, Amy Saray, Annie Wing Hoi Poon, André Laferrière, Terence J Coderre
• Journal: ACS chemical neuroscience (ACS Chem Neurosci) Vol. 6 Issue 11 Pg. 1789-93 (Nov 18 2015) ISSN: 1948-7193 [Electronic] United States
• PMID: 26352668 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• 2',6'-dimethyltyrosyl-arginyl-phenylalanyl-lysinamide
• Analgesics, Opioid
• Antioxidants
• Oligopeptides
• Receptors, Opioid, mu
• Morphine
• Acetylcysteine

Topics

• Acetylcysteine (pharmacology)
• Analgesics, Opioid (chemistry, pharmacology)
• Animals
• Antioxidants (chemistry, pharmacology)
• Area Under Curve
• Chronic Pain (drug therapy, metabolism)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Drug Evaluation, Preclinical
• Drug Synergism
• Hot Temperature
• Hyperalgesia (drug therapy, metabolism)
• Male
• Morphine (pharmacology)
• Oligopeptides (chemistry, pharmacology)
• Rats, Long-Evans
• Receptors, Opioid, mu (agonists, metabolism)
• Reflex Sympathetic Dystrophy (drug therapy, metabolism)
• Touch