Opioid drugs are the principal treatment option for moderate to severe pain and exert their biological effects through interactions with opioid receptors that are widely distributed throughout the CNS and peripheral tissues. Ligands capable of simultaneously targeting different receptors could be successful candidates for the treatment of chronic pain. Enhanced antinociception coupled with a low incidence of side effects has been demonstrated for ligands possessing mixed mu-opioid receptor (MOR) and delta-opioid receptor (DOR) activity. We previously reported that 3-[(2R,6R,11R)-8-hydroxy-6,11-dimethyl-1,4,5,6-tetrahydro-2,6-methano-3-benzazocin-3(2 H)-yl]-N-phenylpropanamide (LP1) acted as a MOR-DOR ligand in in vitro functional assays and moreover this drug produced a valid antinociception that was longer lasting than that of morphine. The aim of this work was to determine whether the antinociceptive effect produced by LP1 was central or peripheral and to assess which opioid receptor subtypes are involved in its effects.

Antinociceptive profile of LP1, a non-peptide multitarget opioid ligand.

PARENTI, Carmela;TURNATURI, RITA;MARRAZZO, Agostino;PREZZAVENTO, Orazio;RONSISVALLE, SIMONE;SCOTO, Giovanna Maria;RONSISVALLE, Giuseppe;PASQUINUCCI, Lorella Giuseppina
2012-01-01

Abstract

Opioid drugs are the principal treatment option for moderate to severe pain and exert their biological effects through interactions with opioid receptors that are widely distributed throughout the CNS and peripheral tissues. Ligands capable of simultaneously targeting different receptors could be successful candidates for the treatment of chronic pain. Enhanced antinociception coupled with a low incidence of side effects has been demonstrated for ligands possessing mixed mu-opioid receptor (MOR) and delta-opioid receptor (DOR) activity. We previously reported that 3-[(2R,6R,11R)-8-hydroxy-6,11-dimethyl-1,4,5,6-tetrahydro-2,6-methano-3-benzazocin-3(2 H)-yl]-N-phenylpropanamide (LP1) acted as a MOR-DOR ligand in in vitro functional assays and moreover this drug produced a valid antinociception that was longer lasting than that of morphine. The aim of this work was to determine whether the antinociceptive effect produced by LP1 was central or peripheral and to assess which opioid receptor subtypes are involved in its effects.
2012
Supraspinal analgesia; 6,7-benzomorphan ligand; Naloxone methiodide; Selective opioid antagonists
File in questo prodotto:
File Dimensione Formato  
Panico A, Maccari R, Cardile V, Crascì L, Ronsisvalle S, Ottanà R..pdf

solo gestori archivio

Licenza: Non specificato
Dimensione 447.77 kB
Formato Adobe PDF
447.77 kB Adobe PDF   Visualizza/Apri

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/20.500.11769/13125
Citazioni
  • ???jsp.display-item.citation.pmc??? 8
  • Scopus 33
  • ???jsp.display-item.citation.isi??? 32
social impact