Low Doses of Allyphenyline and Cyclomethyline, Effective against Morphine Dependence, Elicit an Antidepressant-like Effect.

Abstract

This study demonstrated that cyclomethyline (2) and the corresponding enantiomers (R)-(-)-2 and (S)-(+)-2, displaying α2C-adrenoreceptor (AR) agonism/α2A-AR antagonism, similarly to allyphenyline (1) and its enantiomers, significantly decreased the naloxone-precipitated withdrawal symptoms in mice at very low doses. It also highlighted that such positive effects on morphine dependence can even be improved by additional serotoninergic 5-HT1A receptor (5-HT1A-R) activation. Indeed, 1 or the single (S)-(+)-1, 2, or both its enantiomers, all behaving as α2C-AR agonists/α2A-AR antagonists/5-HT1A-R agonists, alone and at the same low dose, improved morphine withdrawal syndrome and exerted a potent antidepressant-like effect. Therefore, considering the elevated comorbidity between opiate abuse and depressed mood and the benefit of these multifunctional compounds to both disorders, it is possible that they prove more efficacious and less toxic than a cocktail of drugs in managing opioid addiction.

• Authors: Fabio Del Bello, Eleonora Diamanti, Mario Giannella, Valerio Mammoli, Carla Marchioro, Laura Mattioli, Federica Titomanlio, Alessandro Piergentili, Wilma Quaglia, Giovanni Benedetti, Maurizio Varrone, Maria Pigini
• Journal: ACS medicinal chemistry letters (ACS Med Chem Lett) Vol. 3 Issue 7 Pg. 535-9 (Jul 12 2012) ISSN: 1948-5875 [Print] United States
• PMID: 24900506 (Publication Type: Journal Article)