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Abuse Potential and Pharmacodynamic Characteristics of Oral and Intranasal Eluxadoline, a Mixed μ- and κ-Opioid Receptor Agonist and δ-Opioid Receptor Antagonist
Drugs with μ-opioid receptor (OR) activity can be associated with abuse and misuse. The peripherally acting mixed μ-OR and κ-OR agonist and δ-OR antagonist eluxadoline is approved in the United States for the treatment of irritable bowel syndrome with diarrhea. In two separate crossover studies, we...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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The American Society for Pharmacology and Experimental Therapeutics
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5118645/ https://www.ncbi.nlm.nih.gov/pubmed/27647873 http://dx.doi.org/10.1124/jpet.116.236547 |
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author | Levy-Cooperman, N. McIntyre, G. Bonifacio, L. McDonnell, M. Davenport, J. M. Covington, P. S. Dove, L. S. Sellers, E. M. |
author_facet | Levy-Cooperman, N. McIntyre, G. Bonifacio, L. McDonnell, M. Davenport, J. M. Covington, P. S. Dove, L. S. Sellers, E. M. |
author_sort | Levy-Cooperman, N. |
collection | PubMed |
description | Drugs with μ-opioid receptor (OR) activity can be associated with abuse and misuse. The peripherally acting mixed μ-OR and κ-OR agonist and δ-OR antagonist eluxadoline is approved in the United States for the treatment of irritable bowel syndrome with diarrhea. In two separate crossover studies, we evaluated the oral and intranasal abuse potential of eluxadoline versus placebo and the active control oxycodone. Healthy recreational opioid users received eluxadoline 100, 300, and 1000 mg, oxycodone 30 and 60 mg, and placebo (oral study), or eluxadoline 100 and 200 mg, oxycodone 15 and 30 mg, and placebos matched to eluxadoline and oxycodone (intranasal study). In the oral study, Drug Liking Visual Analog Scale (VAS) peak (maximum) effect (E(max)) score (primary endpoint) was significantly greater with eluxadoline 300 and 1000 mg versus placebo, but scores were significantly lower versus oxycodone. Following intranasal insufflation of eluxadoline, Drug Liking VAS E(max) scores were not statistically different versus placebo, and were significantly lower versus oxycodone. Across other subjective measures, eluxadoline was generally similar to or disliked versus placebo. Pupillometry indicated no or minimal central effects with oral and intranasal eluxadoline, respectively. Adverse events of euphoric mood were reported with oral and intranasal eluxadoline but at a far lower frequency versus oxycodone. These data demonstrate that eluxadoline has less abuse potential than oxycodone in recreational opioid users. |
format | Online Article Text |
id | pubmed-5118645 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | The American Society for Pharmacology and Experimental Therapeutics |
record_format | MEDLINE/PubMed |
spelling | pubmed-51186452016-12-15 Abuse Potential and Pharmacodynamic Characteristics of Oral and Intranasal Eluxadoline, a Mixed μ- and κ-Opioid Receptor Agonist and δ-Opioid Receptor Antagonist Levy-Cooperman, N. McIntyre, G. Bonifacio, L. McDonnell, M. Davenport, J. M. Covington, P. S. Dove, L. S. Sellers, E. M. J Pharmacol Exp Ther Behavioral Pharmacology Drugs with μ-opioid receptor (OR) activity can be associated with abuse and misuse. The peripherally acting mixed μ-OR and κ-OR agonist and δ-OR antagonist eluxadoline is approved in the United States for the treatment of irritable bowel syndrome with diarrhea. In two separate crossover studies, we evaluated the oral and intranasal abuse potential of eluxadoline versus placebo and the active control oxycodone. Healthy recreational opioid users received eluxadoline 100, 300, and 1000 mg, oxycodone 30 and 60 mg, and placebo (oral study), or eluxadoline 100 and 200 mg, oxycodone 15 and 30 mg, and placebos matched to eluxadoline and oxycodone (intranasal study). In the oral study, Drug Liking Visual Analog Scale (VAS) peak (maximum) effect (E(max)) score (primary endpoint) was significantly greater with eluxadoline 300 and 1000 mg versus placebo, but scores were significantly lower versus oxycodone. Following intranasal insufflation of eluxadoline, Drug Liking VAS E(max) scores were not statistically different versus placebo, and were significantly lower versus oxycodone. Across other subjective measures, eluxadoline was generally similar to or disliked versus placebo. Pupillometry indicated no or minimal central effects with oral and intranasal eluxadoline, respectively. Adverse events of euphoric mood were reported with oral and intranasal eluxadoline but at a far lower frequency versus oxycodone. These data demonstrate that eluxadoline has less abuse potential than oxycodone in recreational opioid users. The American Society for Pharmacology and Experimental Therapeutics 2016-12 2016-12 /pmc/articles/PMC5118645/ /pubmed/27647873 http://dx.doi.org/10.1124/jpet.116.236547 Text en Copyright © 2016 by The Author(s) http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the CC BY Attribution 4.0 International license (http://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Behavioral Pharmacology Levy-Cooperman, N. McIntyre, G. Bonifacio, L. McDonnell, M. Davenport, J. M. Covington, P. S. Dove, L. S. Sellers, E. M. Abuse Potential and Pharmacodynamic Characteristics of Oral and Intranasal Eluxadoline, a Mixed μ- and κ-Opioid Receptor Agonist and δ-Opioid Receptor Antagonist |
title | Abuse Potential and Pharmacodynamic Characteristics of Oral and Intranasal Eluxadoline, a Mixed μ- and κ-Opioid Receptor Agonist and δ-Opioid Receptor Antagonist |
title_full | Abuse Potential and Pharmacodynamic Characteristics of Oral and Intranasal Eluxadoline, a Mixed μ- and κ-Opioid Receptor Agonist and δ-Opioid Receptor Antagonist |
title_fullStr | Abuse Potential and Pharmacodynamic Characteristics of Oral and Intranasal Eluxadoline, a Mixed μ- and κ-Opioid Receptor Agonist and δ-Opioid Receptor Antagonist |
title_full_unstemmed | Abuse Potential and Pharmacodynamic Characteristics of Oral and Intranasal Eluxadoline, a Mixed μ- and κ-Opioid Receptor Agonist and δ-Opioid Receptor Antagonist |
title_short | Abuse Potential and Pharmacodynamic Characteristics of Oral and Intranasal Eluxadoline, a Mixed μ- and κ-Opioid Receptor Agonist and δ-Opioid Receptor Antagonist |
title_sort | abuse potential and pharmacodynamic characteristics of oral and intranasal eluxadoline, a mixed μ- and κ-opioid receptor agonist and δ-opioid receptor antagonist |
topic | Behavioral Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5118645/ https://www.ncbi.nlm.nih.gov/pubmed/27647873 http://dx.doi.org/10.1124/jpet.116.236547 |
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