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Respir Physiol Neurobiol. 2014 Jan 15;191:95-105. doi: 10.1016/j.resp.2013.11.005. Epub 2013 Nov 24.

Role of central and peripheral opiate receptors in the effects of fentanyl on analgesia, ventilation and arterial blood-gas chemistry in conscious rats.

Author information

  • 1Pediatric Respiratory Medicine, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
  • 2Division of Biology, Galleon Pharmaceuticals, Horsham, PA 19044, USA.
  • 3Department of Pediatrics, Case Western Reserve University, Cleveland, OH 44106-4984, USA. Electronic address: sjl78@case.edu.

Abstract

This study determined the effects of the peripherally restricted μ-opiate receptor (μ-OR) antagonist, naloxone methiodide (NLXmi) on fentanyl (25μg/kg, i.v.)-induced changes in (1) analgesia, (2) arterial blood gas chemistry (ABG) and alveolar-arterial gradient (A-a gradient), and (3) ventilatory parameters, in conscious rats. The fentanyl-induced increase in analgesia was minimally affected by a 1.5mg/kg of NLXmi but was attenuated by a 5.0mg/kg dose. Fentanyl decreased arterial blood pH, pO2 and sO2 and increased pCO2 and A-a gradient. These responses were markedly diminished in NLXmi (1.5mg/kg)-pretreated rats. Fentanyl caused ventilatory depression (e.g., decreases in tidal volume and peak inspiratory flow). Pretreatment with NLXmi (1.5mg/kg, i.v.) antagonized the fentanyl decrease in tidal volume but minimally affected the other responses. These findings suggest that (1) the analgesia and ventilatory depression caused by fentanyl involve peripheral μ-ORs and (2) NLXmi prevents the fentanyl effects on ABG by blocking the negative actions of the opioid on tidal volume and A-a gradient.

KEYWORDS:

Analgesia, Rats; Arterial blood gases; Fentanyl; Naloxone methiodide; Ventilation

PMID:
24284037
PMCID:
PMC4391496
DOI:
10.1016/j.resp.2013.11.005
[PubMed - indexed for MEDLINE]
Free PMC Article
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