TY - JOUR
T1 - The antinociceptive effects of a dual kappa-delta opioid receptor agonist in the mouse formalin test
AU - Ulker, Esad
AU - Toma, Wisam
AU - White, Alyssa
AU - Uprety, Rajendra
AU - Majumdar, Susruta
AU - Damaj, M. Imad
N1 - Publisher Copyright:
Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved
PY - 2020
Y1 - 2020
N2 - Pain management is a challenging and unmet medical need. Despite their demonstrated efficacy, currently used opioid drugs and nonsteroidal anti-inflammatory drugs are frequently associated with several adverse events. The identification of new and safe analgesics is therefore needed. MP1104, an analogue of 3′-iodobenzoyl naltrexamine, is a potent nonselective full agonist at mu (MOR), kappa (KOR), and delta (DOR) opioid receptors, respectively. It was shown to possess potent antinociceptive effects in acute thermal pain assays without aversion in mice. In this study, we investigated MP1104 in the formalin test, a model of tonic pain. MP1104 (0.05, 0.1, and 1.0mg/kg) reduced pain-like behaviors in phases I and II of the formalin test in male and female ICR mice. Pretreatment with KOR antagonist (norbinaltorphimine 10mg/kg) and DOR antagonist (naltrindole 10mg/kg) abolished the antinociceptive effects of MP1104 in the formalin test. These findings support the development of MP1104 for further testing in other pain models.
AB - Pain management is a challenging and unmet medical need. Despite their demonstrated efficacy, currently used opioid drugs and nonsteroidal anti-inflammatory drugs are frequently associated with several adverse events. The identification of new and safe analgesics is therefore needed. MP1104, an analogue of 3′-iodobenzoyl naltrexamine, is a potent nonselective full agonist at mu (MOR), kappa (KOR), and delta (DOR) opioid receptors, respectively. It was shown to possess potent antinociceptive effects in acute thermal pain assays without aversion in mice. In this study, we investigated MP1104 in the formalin test, a model of tonic pain. MP1104 (0.05, 0.1, and 1.0mg/kg) reduced pain-like behaviors in phases I and II of the formalin test in male and female ICR mice. Pretreatment with KOR antagonist (norbinaltorphimine 10mg/kg) and DOR antagonist (naltrindole 10mg/kg) abolished the antinociceptive effects of MP1104 in the formalin test. These findings support the development of MP1104 for further testing in other pain models.
UR - http://www.scopus.com/inward/record.url?scp=85082092969&partnerID=8YFLogxK
U2 - 10.1097/FBP.0000000000000541
DO - 10.1097/FBP.0000000000000541
M3 - Article
C2 - 32168026
AN - SCOPUS:85082092969
SN - 0955-8810
VL - 31
SP - 174
EP - 178
JO - Behavioural Pharmacology
JF - Behavioural Pharmacology
IS - 2-3
ER -