N-(2-morpholin-4-yl-ethyl)-2-(1naphthyloxy)acetamide inhibits the chronic constriction injury-generated hyperalgesia via the antagonism of sigma-1 receptors

Josué Vidal Espinosa-Juárez, Osmar Antonio Jaramillo-Morales, Gabriel Navarrete-Vázquez, Luis Alberto Melo-Hernández, Myrna Déciga-Campos, Francisco Javier López-Muñoz

Research output: Contribution to journalArticle

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Abstract

© 2017 The most used therapeutic treatment to relieve neuropathic pain is that of neuromodulators such as anti-epileptics or anti-depressants; however, there are alternatives that may be potentially useful. The sigma-1 receptor is a therapeutic target that has shown favorable results at preclinical levels. The aim of this study was to evaluate the anti-hyperalgesic effect of N-(2-morpholin-4-yl-ethyl)-2-(1-naphthyloxy) acetamide (NMIN) in a chronic constriction injury model (CCI) and compare it both a sigma-1 antagonist (BD-1063) and also Gabapentin, as well as determine its possible role as an antagonist of sigma-1 receptors. The anti-hyperalgesic effects of Gabapentin (10.0, 17.8, 31.6, 56.2 and 100 mg/kg, s.c.), BD-1063 (5.6, 10.0, 17.8, 31.6 and 56.2 mg/kg, s.c.) and NMIN (31.6, 10.0, 316 mg/kg and 562 mg/kg, s.c.) were determined after single-doses, using the von Frey test in the CCI model. NMIN had the same efficacy as BD-1063, but both show less efficacy than Gabapentin. In an analysis of pharmacological potency, the ED50 were compared with it being found that BD-1063 is the most potent drug, followed by Gabapentin and NMIN. The anti-hyperalgesic effect of NMIN on CCI rats was reversed by (+)-pentazocine (s.c. route) and by PRE-084 (i.t. route), both sigma-1 agonists. Furthermore, NMIN reversed the hyperalgesic effect of PRE-084 in naïve rats. These results suggest that NMIN has an anti-hyperalgesic effect on the CCI model, and that one of its mechanisms of action is as a sigma-1 antagonist, being a significant role the blocking of these receptors at the spinal level.
Original languageAmerican English
Pages (from-to)1-8
Number of pages0
JournalEuropean Journal of Pharmacology
DOIs
StatePublished - 1 Jan 2017

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Hyperalgesia
Constriction
Wounds and Injuries
Pentazocine
Neuralgia
Neurotransmitter Agents
Therapeutics
Pharmacology
1-(2-(3,4-dichlorophenyl)ethyl)-4-methylpiperazine
sigma-1 receptor
gabapentin
acetamide
Pharmaceutical Preparations
2-(4-morpholino)ethyl-1-phenylcyclohexane-1-carboxylate

Cite this

Espinosa-Juárez, Josué Vidal ; Jaramillo-Morales, Osmar Antonio ; Navarrete-Vázquez, Gabriel ; Melo-Hernández, Luis Alberto ; Déciga-Campos, Myrna ; López-Muñoz, Francisco Javier. / N-(2-morpholin-4-yl-ethyl)-2-(1naphthyloxy)acetamide inhibits the chronic constriction injury-generated hyperalgesia via the antagonism of sigma-1 receptors. In: European Journal of Pharmacology. 2017 ; pp. 1-8.
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abstract = "{\circledC} 2017 The most used therapeutic treatment to relieve neuropathic pain is that of neuromodulators such as anti-epileptics or anti-depressants; however, there are alternatives that may be potentially useful. The sigma-1 receptor is a therapeutic target that has shown favorable results at preclinical levels. The aim of this study was to evaluate the anti-hyperalgesic effect of N-(2-morpholin-4-yl-ethyl)-2-(1-naphthyloxy) acetamide (NMIN) in a chronic constriction injury model (CCI) and compare it both a sigma-1 antagonist (BD-1063) and also Gabapentin, as well as determine its possible role as an antagonist of sigma-1 receptors. The anti-hyperalgesic effects of Gabapentin (10.0, 17.8, 31.6, 56.2 and 100 mg/kg, s.c.), BD-1063 (5.6, 10.0, 17.8, 31.6 and 56.2 mg/kg, s.c.) and NMIN (31.6, 10.0, 316 mg/kg and 562 mg/kg, s.c.) were determined after single-doses, using the von Frey test in the CCI model. NMIN had the same efficacy as BD-1063, but both show less efficacy than Gabapentin. In an analysis of pharmacological potency, the ED50 were compared with it being found that BD-1063 is the most potent drug, followed by Gabapentin and NMIN. The anti-hyperalgesic effect of NMIN on CCI rats was reversed by (+)-pentazocine (s.c. route) and by PRE-084 (i.t. route), both sigma-1 agonists. Furthermore, NMIN reversed the hyperalgesic effect of PRE-084 in na{\"i}ve rats. These results suggest that NMIN has an anti-hyperalgesic effect on the CCI model, and that one of its mechanisms of action is as a sigma-1 antagonist, being a significant role the blocking of these receptors at the spinal level.",
author = "Espinosa-Ju{\'a}rez, {Josu{\'e} Vidal} and Jaramillo-Morales, {Osmar Antonio} and Gabriel Navarrete-V{\'a}zquez and Melo-Hern{\'a}ndez, {Luis Alberto} and Myrna D{\'e}ciga-Campos and L{\'o}pez-Mu{\~n}oz, {Francisco Javier}",
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N-(2-morpholin-4-yl-ethyl)-2-(1naphthyloxy)acetamide inhibits the chronic constriction injury-generated hyperalgesia via the antagonism of sigma-1 receptors. / Espinosa-Juárez, Josué Vidal; Jaramillo-Morales, Osmar Antonio; Navarrete-Vázquez, Gabriel; Melo-Hernández, Luis Alberto; Déciga-Campos, Myrna; López-Muñoz, Francisco Javier.

In: European Journal of Pharmacology, 01.01.2017, p. 1-8.

Research output: Contribution to journalArticle

TY - JOUR

T1 - N-(2-morpholin-4-yl-ethyl)-2-(1naphthyloxy)acetamide inhibits the chronic constriction injury-generated hyperalgesia via the antagonism of sigma-1 receptors

AU - Espinosa-Juárez, Josué Vidal

AU - Jaramillo-Morales, Osmar Antonio

AU - Navarrete-Vázquez, Gabriel

AU - Melo-Hernández, Luis Alberto

AU - Déciga-Campos, Myrna

AU - López-Muñoz, Francisco Javier

PY - 2017/1/1

Y1 - 2017/1/1

N2 - © 2017 The most used therapeutic treatment to relieve neuropathic pain is that of neuromodulators such as anti-epileptics or anti-depressants; however, there are alternatives that may be potentially useful. The sigma-1 receptor is a therapeutic target that has shown favorable results at preclinical levels. The aim of this study was to evaluate the anti-hyperalgesic effect of N-(2-morpholin-4-yl-ethyl)-2-(1-naphthyloxy) acetamide (NMIN) in a chronic constriction injury model (CCI) and compare it both a sigma-1 antagonist (BD-1063) and also Gabapentin, as well as determine its possible role as an antagonist of sigma-1 receptors. The anti-hyperalgesic effects of Gabapentin (10.0, 17.8, 31.6, 56.2 and 100 mg/kg, s.c.), BD-1063 (5.6, 10.0, 17.8, 31.6 and 56.2 mg/kg, s.c.) and NMIN (31.6, 10.0, 316 mg/kg and 562 mg/kg, s.c.) were determined after single-doses, using the von Frey test in the CCI model. NMIN had the same efficacy as BD-1063, but both show less efficacy than Gabapentin. In an analysis of pharmacological potency, the ED50 were compared with it being found that BD-1063 is the most potent drug, followed by Gabapentin and NMIN. The anti-hyperalgesic effect of NMIN on CCI rats was reversed by (+)-pentazocine (s.c. route) and by PRE-084 (i.t. route), both sigma-1 agonists. Furthermore, NMIN reversed the hyperalgesic effect of PRE-084 in naïve rats. These results suggest that NMIN has an anti-hyperalgesic effect on the CCI model, and that one of its mechanisms of action is as a sigma-1 antagonist, being a significant role the blocking of these receptors at the spinal level.

AB - © 2017 The most used therapeutic treatment to relieve neuropathic pain is that of neuromodulators such as anti-epileptics or anti-depressants; however, there are alternatives that may be potentially useful. The sigma-1 receptor is a therapeutic target that has shown favorable results at preclinical levels. The aim of this study was to evaluate the anti-hyperalgesic effect of N-(2-morpholin-4-yl-ethyl)-2-(1-naphthyloxy) acetamide (NMIN) in a chronic constriction injury model (CCI) and compare it both a sigma-1 antagonist (BD-1063) and also Gabapentin, as well as determine its possible role as an antagonist of sigma-1 receptors. The anti-hyperalgesic effects of Gabapentin (10.0, 17.8, 31.6, 56.2 and 100 mg/kg, s.c.), BD-1063 (5.6, 10.0, 17.8, 31.6 and 56.2 mg/kg, s.c.) and NMIN (31.6, 10.0, 316 mg/kg and 562 mg/kg, s.c.) were determined after single-doses, using the von Frey test in the CCI model. NMIN had the same efficacy as BD-1063, but both show less efficacy than Gabapentin. In an analysis of pharmacological potency, the ED50 were compared with it being found that BD-1063 is the most potent drug, followed by Gabapentin and NMIN. The anti-hyperalgesic effect of NMIN on CCI rats was reversed by (+)-pentazocine (s.c. route) and by PRE-084 (i.t. route), both sigma-1 agonists. Furthermore, NMIN reversed the hyperalgesic effect of PRE-084 in naïve rats. These results suggest that NMIN has an anti-hyperalgesic effect on the CCI model, and that one of its mechanisms of action is as a sigma-1 antagonist, being a significant role the blocking of these receptors at the spinal level.

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