TY - JOUR
T1 - In vivo apparent affinity and efficacy estimates for mu opiates in a rat tail-withdrawal assay.
AU - Walker, E A
AU - Zernig, G
AU - Young, Alice
N1 - Funding Information:
These experiments were performed in accordance with the Guide for the Care and Use of Laboratory Animals (NIH pub. no. 86-23, revised 1996). This work was supported by US Public Health Service Grants DA03796 (A.M.Y.) and DA07947 (E.A.W.), NIDA Research Scientist Development Award K02 DA00132 (A.M.Y.), and a NIDA INVEST Fellowship (G.Z.)
PY - 1998/3/1
Y1 - 1998/3/1
N2 - Experiments in a rat tail-withdrawal assay tested the hypothesis that the magnitude and pattern of antagonism of μ opiate agonists by the insurmountable μ opioid antagonist clocinnamox are inversely related to agonist efficacy. In addition, these experiments examined whether this antagonism could be quantified to yield apparent affinity and efficacy estimates for the pharmacological characterization of five opiate agonists. Etonitazene, etorphine, morphine, buprenorphine, and GPA 1657 produced dose-dependent increases in tail-withdrawal latency until 100% maximum possible effect (%MPE) was obtained. Morphine required a higher dose of clocinnamox for a 50% reduction in maximal antinociceptive effect than did buprenorphine or GPA 1657. In contrast, no dose of clocinnamox tested decreased the %MPE for etonitazene or etorphine. These data suggest a rank order of relative efficacy of etonitazene ≤ etorphine > morphine ≤ GPA 1657 ≤ buprenorphine. Similarly, numerical analysis of these data yielded the following apparent affinity and efficacy estimates: etonitazene (0.35 mg/kg, 128); etorphine (0.68 mg/kg, 125); morphine (50 mg/kg, 38), GPA 1657 (6.6, 39); and buprenorphine (0.042 mg/kg, 2.2). These data illustrate that in vivo affinity and efficacy estimates for a number of agonists are remarkably similar across different methods of analysis and are useful for drug classification.
AB - Experiments in a rat tail-withdrawal assay tested the hypothesis that the magnitude and pattern of antagonism of μ opiate agonists by the insurmountable μ opioid antagonist clocinnamox are inversely related to agonist efficacy. In addition, these experiments examined whether this antagonism could be quantified to yield apparent affinity and efficacy estimates for the pharmacological characterization of five opiate agonists. Etonitazene, etorphine, morphine, buprenorphine, and GPA 1657 produced dose-dependent increases in tail-withdrawal latency until 100% maximum possible effect (%MPE) was obtained. Morphine required a higher dose of clocinnamox for a 50% reduction in maximal antinociceptive effect than did buprenorphine or GPA 1657. In contrast, no dose of clocinnamox tested decreased the %MPE for etonitazene or etorphine. These data suggest a rank order of relative efficacy of etonitazene ≤ etorphine > morphine ≤ GPA 1657 ≤ buprenorphine. Similarly, numerical analysis of these data yielded the following apparent affinity and efficacy estimates: etonitazene (0.35 mg/kg, 128); etorphine (0.68 mg/kg, 125); morphine (50 mg/kg, 38), GPA 1657 (6.6, 39); and buprenorphine (0.042 mg/kg, 2.2). These data illustrate that in vivo affinity and efficacy estimates for a number of agonists are remarkably similar across different methods of analysis and are useful for drug classification.
M3 - Article
SN - 0033-3158
SP - 15
EP - 23
JO - Psychopharmacology
JF - Psychopharmacology
ER -