title: Role of central and peripheral opiate receptors in the effects of fentanyl on analgesia, ventilation and arterial blood-gas chemistry in conscious rats.
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.
authors.affiliation: Pediatric Respiratory Medicine, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
authors.forename: Fraser
authors.initials: F
authors.lastname: Henderson
authors.affiliation: Pediatric Respiratory Medicine, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
authors.forename: Walter J
authors.initials: WJ
authors.lastname: May
authors.affiliation: Division of Biology, Galleon Pharmaceuticals, Horsham, PA 19044, USA.
authors.forename: Ryan B
authors.initials: RB
authors.lastname: Gruber
authors.affiliation: Division of Biology, Galleon Pharmaceuticals, Horsham, PA 19044, USA.
authors.forename: Joseph F
authors.initials: JF
authors.lastname: Discala
authors.affiliation: Division of Biology, Galleon Pharmaceuticals, Horsham, PA 19044, USA.
authors.forename: Veljko
authors.initials: V
authors.lastname: Puskovic
authors.affiliation: Pediatric Respiratory Medicine, University of Virginia School of Medicine, Charlottesville, VA 22908, USA.
authors.forename: Alex P
authors.initials: AP
authors.lastname: Young
authors.affiliation: Division of Biology, Galleon Pharmaceuticals, Horsham, PA 19044, USA.
authors.forename: Santhosh M
authors.initials: SM
authors.lastname: Baby
authors.affiliation: Department of Pediatrics, Case Western Reserve University, Cleveland, OH 44106-4984, USA. Electronic address: sjl78@case.edu.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Lewis
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000187:drug effects; D001831:Body Temperature / Q000187:drug effects; D003243:Consciousness / Q000187:drug effects* / Q000502:physiology; D005283:Fentanyl / Q000494:pharmacology*; D006930:Hyperalgesia / Q000188:drug therapy; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D012119:Respiration / Q000187:drug effects*; D013990:Tidal Volume / Q000187:drug effects
chemical_list: D009292:Narcotic Antagonists; D009294:Narcotics; D009270:Naloxone; D005283:Fentanyl
keywords: Analgesia, Rats; Arterial blood gases; Fentanyl; Naloxone methiodide; Ventilation