Might Adrenergic α2C-Agonists/α2A-Antagonists Become Novel Therapeutic Tools for Pain Treatment with Morphine?

The imidazoline nucleus linked in position 2 via an oxyethylene bridge to a phenyl ring carrying an ortho substituent of moderate steric bulk provided α2-adrenergic (AR) ligands endowed with significant α2C-agonism/α2A-antagonism. Similar behavior was displayed by cirazoline (12). For their positive morphine analgesia modulation (due to α2C-AR stimulation) and sedation overcoming (due to α2A-AR antagonism), 8 and 11 might be useful as adjuvant agents in the management of pain with morphine.