Naloxone pro-drug rescues morphine induced respiratory depression in Sprague-Dawley rats

Michael Wallisch, Nehad M. El Rody, Baohua Huang, Dennis Koop, James R. Baker, George D. Olsen

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Respiratory depression is the main obstacle for the safe administration of morphine for acute pain after injury. Due to this complication, new delivery methods are needed to insure that safe and effective doses of opioid analgesics are administered during emergencies. A depot formulation containing a naloxone pro-drug was designed to release the antidote when morphine causes dangerous hypoxic conditions in the blood. The aim of this work was to test the naloxone release in vivo in response to a severe overdose of morphine in the Sprague-Dawley rat model. Non-invasive two-chamber plethysmography was used to monitor and record respiration and to test the capability of the naloxone pro-drug to respond to and rescue morphine-induced respiratory depression in the animal. We show that the pro-drug formulation can both prevent and reverse severe morphine induced respiratory depression. The animal model demonstrates that co-administration of the naloxone pro-drug reliably antagonizes profound respiratory depressive effects of morphine.

Original languageEnglish (US)
Pages (from-to)52-60
Number of pages9
JournalRespiratory Physiology and Neurobiology
Volume180
Issue number1
DOIs
StatePublished - Jan 15 2012

Fingerprint

Drug Repositioning
Prodrugs
Naloxone
Respiratory Insufficiency
Morphine
Sprague Dawley Rats
Antidotes
Drug Compounding
Plethysmography
Acute Pain
Opioid Analgesics
Respiration
Emergencies
Animal Models
Wounds and Injuries

Keywords

  • Delivery vehicle
  • Morphine
  • Naloxone
  • Respiratory depression

ASJC Scopus subject areas

  • Physiology
  • Pulmonary and Respiratory Medicine
  • Neuroscience(all)

Cite this

Naloxone pro-drug rescues morphine induced respiratory depression in Sprague-Dawley rats. / Wallisch, Michael; El Rody, Nehad M.; Huang, Baohua; Koop, Dennis; Baker, James R.; Olsen, George D.

In: Respiratory Physiology and Neurobiology, Vol. 180, No. 1, 15.01.2012, p. 52-60.

Research output: Contribution to journalArticle

Wallisch, Michael ; El Rody, Nehad M. ; Huang, Baohua ; Koop, Dennis ; Baker, James R. ; Olsen, George D. / Naloxone pro-drug rescues morphine induced respiratory depression in Sprague-Dawley rats. In: Respiratory Physiology and Neurobiology. 2012 ; Vol. 180, No. 1. pp. 52-60.
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