Low Doses of Allyphenyline
and Cyclomethyline, Effective
against Morphine Dependence, Elicit an Antidepressant-like Effect
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Abstract
This study demonstrated that cyclomethyline (<b>2</b>) and
the corresponding enantiomers (<i>R</i>)-(−)-<b>2</b> and (<i>S</i>)-(+)-<b>2</b>, displaying
α<sub>2C</sub>-adrenoreceptor (AR) agonism/α<sub>2A</sub>-AR antagonism, similarly to allyphenyline (<b>1</b>) 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<sub>1A</sub> receptor (5-HT<sub>1A</sub>-R) activation.
Indeed, <b>1</b> or the single (<i>S</i>)-(+)-<b>1</b>, <b>2</b>, or both its enantiomers, all behaving as
α<sub>2C</sub>-AR agonists/α<sub>2A</sub>-AR antagonists/5-HT<sub>1A</sub>-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