Multitarget Opioid/Non-opioid Ligands: A Potential Approach in Pain Management

Polypharmacology, or the associations between two or more drugs producing biologicaleffects on two or more different sites of action could represent a possible therapeuticapproach for the clinical management of acute and chronic pain. The multitude and complexityof neuronal mechanisms that contribute to pain transmission provide several possible targetsfor pharmacological intervention. Thus, multitarget ligands possessing opioid-opioid ornon-opioid-opioid mechanisms of action are potential drug candidates for pain relief. In thisperspective, the past medicinal chemistry paradigm “one-target, one-disease” has been reconsideredand converted into “one-molecule, multiple targets”. Multitarget ligands in comparisonwith cocktail drugs, besides an improved analgesic effect, display a more predictablepharmacokinetic and pharmacodynamic profile coupled to a less incidence of side-effects.Thus, they ameliorate patient compliance and decrease the risk of drug-drug interactions. Inour previous review multitarget ligands with an opioid-opioid mechanism of action weredescribed. Here, we deal with multitarget ligands with opioid-non opioid mechanism of actionas potential drug candidates for the management of different pain states.