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

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• 作者：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
• 刊名：ACS Medicinal Chemistry Letters
• 出版年：2012
• 出版时间：July 12, 2012
• 年：2012
• 卷：3
• 期：7
• 页码：535-539
• 全文大小：291K
• 年卷期：v.3,no.7(July 12, 2012)
• ISSN：1948-5875

文摘

This study demonstrated that cyclomethyline (2) and the corresponding enantiomers (R)-(鈭?-2 and (S)-(+)-2, displaying 伪_2C-adrenoreceptor (AR) agonism/伪_2A-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-HT_1A receptor (5-HT_1A-R) activation. Indeed, 1 or the single (S)-(+)-1, 2, or both its enantiomers, all behaving as 伪_2C-AR agonists/伪_2A-AR antagonists/5-HT_1A-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.

Keywords:

伪₂-adrenergic ligands; 5-HT_1A-R agonists; morphine withdrawal symptoms reduction; antidepressant-like effect