Exploring Multitarget Interactions to Reduce OpiateWithdrawal Syndrome and Psychiatric Comorbidity

摘要

Opioid addiction is often characterized as a chronic relapsing condition due to the severe somatic and behavioral signs, associated with depressive disorders, triggered by opiate withdrawal. Since prolonged abstinence remains a major challenge, our interest has been addressed to such objective. Exploring multitarget interactions, the present investigation suggests that >3 or its (S)-enantiomer and >4, endowed with effective α2C-AR agonism/α2A-AR antagonism/5-HT1A-R agonism, or >7 and >9–>11 producing efficacious α2C-AR agonism/α2A-AR antagonism/I2–IBS interaction might represent novel multifunctional tools potentially useful for reducing withdrawal syndrome and associated depression. Such agents, lacking in sedative side effects due to their α2A-AR antagonism, might afford an improvement over current therapies with clonidine-like drugs.