Reversal by β‐funaltrexamine of the antinociceptive effect of opioid agonists in the rat

Abstract

1 The effect of the irreversible opioid receptor antagonist, β-funaltrexamine (β-FNA), on antin-ociception produced by μ- and κ-receptor agonists was studied in the rat. 2 β-FNA, 20 to 80 mg kg⁻¹, s.c., given 24 h before testing, produced a dose-related antagonism of the effects of morphine in the paw pressure, hotplate and tail-flick tests. Following the 80 mg kg⁻¹ dose, the degree of antagonism of morphine was stable for up to 48 h after dosing, but was reduced by 5 days and had disappeared by 8 days. 3 In the paw pressure test, β-FNA, 40 mg kg⁻¹, s.c., antagonized the effects of fentanyl, buprenorphine, tifluadom, ethylketocyclazocine and proxorphan; it was without effect against the highly selective κ-agonist, U-50,488. 4 In light of these results, the possible opioid receptor selectivities of both the agonists and β-FNA are reassessed.