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.
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