2020
DOI: 10.1111/head.14019
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A non‐convulsant delta‐opioid receptor agonist, KNT‐127, reduces cortical spreading depression and nitroglycerin‐induced allodynia

Abstract: Objective: The aim of this study was to determine if the non-convulsant delta-opioid receptor (DOR) agonist, KNT-127, could inhibit migraine-associated endpoints. Background: The DOR has been identified as a therapeutic target for migraine. However, the development of delta agonists is limited as some ligands have seizurogenic properties, which may be related to their ability to induce receptor internalization. While both pro-and non-convulsant delta agonists can reduce migraine-associated allodynia, only the … Show more

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Cited by 17 publications
(20 citation statements)
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“…The translational utility of this test has been crucial to investigate the underlying mechanisms of several migraine treatments and to predict the efficacy of new therapies. Some of the treatments positively tested to date include triptans (68,69), which in turn are also used as a positive control in these tests; gepants (69); CGRP monoclonal antibodies (69); ditans (70); and opioid receptor agonists (71).…”
Section: Use Of Allodynia As a Readout Of Migraine-like Pain In Preclinical Modelsmentioning
confidence: 99%
“…The translational utility of this test has been crucial to investigate the underlying mechanisms of several migraine treatments and to predict the efficacy of new therapies. Some of the treatments positively tested to date include triptans (68,69), which in turn are also used as a positive control in these tests; gepants (69); CGRP monoclonal antibodies (69); ditans (70); and opioid receptor agonists (71).…”
Section: Use Of Allodynia As a Readout Of Migraine-like Pain In Preclinical Modelsmentioning
confidence: 99%
“…As reported previously [37, 44, 45], this dosing regimen produced significant cephalic allodynia (Figure 2B). We tested mice in the CSD model [28, 37, 39, 46] on day 5, ∼16 hours after the final morphine treatment. Mice were recorded for an hour during continual administration of 1M KCl directly onto the dura.…”
Section: Resultsmentioning
confidence: 99%
“…The model of cortical spreading depression (CSD) used in these studies is based on previously published work [28, 37, 38]. Mice were randomly grouped into Vehicle or M65 (0.1 mg/kg, IP).…”
Section: Methodsmentioning
confidence: 99%
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“…The procedure for the cortical spreading depression (CSD) model is based on previously published work ( Chen and Ayata, 2017 ) that is commonly used to screen potential migraine preventives and further used in our own work ( Pradhan et al, 2014b ; Dripps et al, 2020 ; Bertels et al, 2021 ). Mice were grouped into sham and CSD groups and then further subdivide into ACY-738 (50 mg/kg, IP) or vehicle (i.e.…”
Section: Methodsmentioning
confidence: 99%