A possible therapeutic approach for the clinical management of acute and chronic pain is polypharmacology,or the associations between two or more drugs producing biological effects on two or more different sites of action, by modulating directly or indirectly the analgesic profile and possible adverse effects. Today, considering the benefits ofpolypharmacology in the drug discovery process the "one-molecule multiple target" strategy has been recognized. For multitarget ligands a better analgesic activity with fewer side effects – detected in the association of drugs – coupled withfavourable pharmacokinetic and pharmacodynamic characteristics have been proven. Given that the various mediatorsinvolved in the circuit of pain represent potential targets for different pharmacological interventions, multitarget ligands possessing opioid-opioid or non-opioid-opioid mechanisms of action are potential drug candidates for the management of various pain conditions. Low propensity to induce side effects was reported for multitarget ligands, able to act simultaneously on multiple opioid receptors subtypes. In particular, an improved analgesic profile associated with a reduced tolerance-inducing capability was found in mixed MOR (mu-opioid receptor)-DOR (delta-opioid receptor)ligands. In this context, the benzomorphan-based compound LP1 belongs to the class of multitarget ligand. In thismanuscript the pharmacological fingerprint of LP1 as suitable drug candidate in pain relief is described.

The Benzomorphan-Based Compound LP1 as Suitable Candidate for Pain Management

PASQUINUCCI, Lorella Giuseppina;Turnaturi R
;
Parenti C;
2016-01-01

Abstract

A possible therapeutic approach for the clinical management of acute and chronic pain is polypharmacology,or the associations between two or more drugs producing biological effects on two or more different sites of action, by modulating directly or indirectly the analgesic profile and possible adverse effects. Today, considering the benefits ofpolypharmacology in the drug discovery process the "one-molecule multiple target" strategy has been recognized. For multitarget ligands a better analgesic activity with fewer side effects – detected in the association of drugs – coupled withfavourable pharmacokinetic and pharmacodynamic characteristics have been proven. Given that the various mediatorsinvolved in the circuit of pain represent potential targets for different pharmacological interventions, multitarget ligands possessing opioid-opioid or non-opioid-opioid mechanisms of action are potential drug candidates for the management of various pain conditions. Low propensity to induce side effects was reported for multitarget ligands, able to act simultaneously on multiple opioid receptors subtypes. In particular, an improved analgesic profile associated with a reduced tolerance-inducing capability was found in mixed MOR (mu-opioid receptor)-DOR (delta-opioid receptor)ligands. In this context, the benzomorphan-based compound LP1 belongs to the class of multitarget ligand. In thismanuscript the pharmacological fingerprint of LP1 as suitable drug candidate in pain relief is described.
Opioids, chronic pain; tolerance; chronic constriction injury (CCI) ; Carrageenan-induced inflammatory; Micro-electrode array (MEA); Differential scanning calorimetry (DSC)
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11769/29970
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