Chronic methadone treatment shows a better cost/benefit ratio than chronic morphine in mice

Johan Enquist, Madeline Ferwerda, Laura Milan-Lobo, Jennifer Whistler

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Chronic treatment of pain with opiate drugs can lead to analgesic tolerance and drug dependence. Although all opiate drugs can promote tolerance and dependence in practice, the severity of those unwanted side effects differs depending on the drug used. Although each opiate drug has its own unique set of pharmacological profiles, methadone is the only clinically used opioid drug that produces substantial receptor endocytosis at analgesic doses. Here, we examined whether moderate doses of methadone carry any benefits over chronic use of equianalgesic morphine, the prototypical opioid. Our data show that chronic administration of methadone produces significantly less analgesic tolerance than morphine. Furthermore, we found significantly reduced precipitated withdrawal symptoms after chronic methadone treatment than after chronic morphine treatment. Finally, using a novel animal model with a degrading μ-opioid receptor we showed that, although endocytosis seems to protect against tolerance development, endocytosis followed by receptor degradation produces a rapid onset of analgesic tolerance to methadone. Together, these data indicated that opioid drugs that promote receptor endocytosis and recycling, such as methadone, may be a better choice for chronic pain treatment than morphine and its derivatives that do not.

Original languageEnglish (US)
Pages (from-to)386-392
Number of pages7
JournalJournal of Pharmacology and Experimental Therapeutics
Volume340
Issue number2
DOIs
StatePublished - Feb 1 2012
Externally publishedYes

Fingerprint

Methadone
Morphine
Cost-Benefit Analysis
Opiate Alkaloids
Endocytosis
Analgesics
Opioid Analgesics
Pharmaceutical Preparations
Chronic Pain
Morphine Derivatives
Therapeutics
Drug Receptors
Substance Withdrawal Syndrome
Recycling
Opioid Receptors
Substance-Related Disorders
Animal Models
Pharmacology

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

Cite this

Chronic methadone treatment shows a better cost/benefit ratio than chronic morphine in mice. / Enquist, Johan; Ferwerda, Madeline; Milan-Lobo, Laura; Whistler, Jennifer.

In: Journal of Pharmacology and Experimental Therapeutics, Vol. 340, No. 2, 01.02.2012, p. 386-392.

Research output: Contribution to journalArticle

@article{fc5d3d93605246c0a17fb8276481f18d,
title = "Chronic methadone treatment shows a better cost/benefit ratio than chronic morphine in mice",
abstract = "Chronic treatment of pain with opiate drugs can lead to analgesic tolerance and drug dependence. Although all opiate drugs can promote tolerance and dependence in practice, the severity of those unwanted side effects differs depending on the drug used. Although each opiate drug has its own unique set of pharmacological profiles, methadone is the only clinically used opioid drug that produces substantial receptor endocytosis at analgesic doses. Here, we examined whether moderate doses of methadone carry any benefits over chronic use of equianalgesic morphine, the prototypical opioid. Our data show that chronic administration of methadone produces significantly less analgesic tolerance than morphine. Furthermore, we found significantly reduced precipitated withdrawal symptoms after chronic methadone treatment than after chronic morphine treatment. Finally, using a novel animal model with a degrading μ-opioid receptor we showed that, although endocytosis seems to protect against tolerance development, endocytosis followed by receptor degradation produces a rapid onset of analgesic tolerance to methadone. Together, these data indicated that opioid drugs that promote receptor endocytosis and recycling, such as methadone, may be a better choice for chronic pain treatment than morphine and its derivatives that do not.",
author = "Johan Enquist and Madeline Ferwerda and Laura Milan-Lobo and Jennifer Whistler",
year = "2012",
month = "2",
day = "1",
doi = "10.1124/jpet.111.187583",
language = "English (US)",
volume = "340",
pages = "386--392",
journal = "Journal of Pharmacology and Experimental Therapeutics",
issn = "0022-3565",
publisher = "American Society for Pharmacology and Experimental Therapeutics",
number = "2",

}

TY - JOUR

T1 - Chronic methadone treatment shows a better cost/benefit ratio than chronic morphine in mice

AU - Enquist, Johan

AU - Ferwerda, Madeline

AU - Milan-Lobo, Laura

AU - Whistler, Jennifer

PY - 2012/2/1

Y1 - 2012/2/1

N2 - Chronic treatment of pain with opiate drugs can lead to analgesic tolerance and drug dependence. Although all opiate drugs can promote tolerance and dependence in practice, the severity of those unwanted side effects differs depending on the drug used. Although each opiate drug has its own unique set of pharmacological profiles, methadone is the only clinically used opioid drug that produces substantial receptor endocytosis at analgesic doses. Here, we examined whether moderate doses of methadone carry any benefits over chronic use of equianalgesic morphine, the prototypical opioid. Our data show that chronic administration of methadone produces significantly less analgesic tolerance than morphine. Furthermore, we found significantly reduced precipitated withdrawal symptoms after chronic methadone treatment than after chronic morphine treatment. Finally, using a novel animal model with a degrading μ-opioid receptor we showed that, although endocytosis seems to protect against tolerance development, endocytosis followed by receptor degradation produces a rapid onset of analgesic tolerance to methadone. Together, these data indicated that opioid drugs that promote receptor endocytosis and recycling, such as methadone, may be a better choice for chronic pain treatment than morphine and its derivatives that do not.

AB - Chronic treatment of pain with opiate drugs can lead to analgesic tolerance and drug dependence. Although all opiate drugs can promote tolerance and dependence in practice, the severity of those unwanted side effects differs depending on the drug used. Although each opiate drug has its own unique set of pharmacological profiles, methadone is the only clinically used opioid drug that produces substantial receptor endocytosis at analgesic doses. Here, we examined whether moderate doses of methadone carry any benefits over chronic use of equianalgesic morphine, the prototypical opioid. Our data show that chronic administration of methadone produces significantly less analgesic tolerance than morphine. Furthermore, we found significantly reduced precipitated withdrawal symptoms after chronic methadone treatment than after chronic morphine treatment. Finally, using a novel animal model with a degrading μ-opioid receptor we showed that, although endocytosis seems to protect against tolerance development, endocytosis followed by receptor degradation produces a rapid onset of analgesic tolerance to methadone. Together, these data indicated that opioid drugs that promote receptor endocytosis and recycling, such as methadone, may be a better choice for chronic pain treatment than morphine and its derivatives that do not.

UR - http://www.scopus.com/inward/record.url?scp=84855999372&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84855999372&partnerID=8YFLogxK

U2 - 10.1124/jpet.111.187583

DO - 10.1124/jpet.111.187583

M3 - Article

C2 - 22062352

AN - SCOPUS:84855999372

VL - 340

SP - 386

EP - 392

JO - Journal of Pharmacology and Experimental Therapeutics

JF - Journal of Pharmacology and Experimental Therapeutics

SN - 0022-3565

IS - 2

ER -