Comparison of physical dependence of ohmefentanyl stereoisomers in mice

Stereo-structural difference of ohmefentanyl stereoisomers on analgesic act ion and receptor affinity has been studied. To assess the difference of ohm efentanyl stereoisomers in physical dependence, the potency of physical dep endence was quantified by estimating the ED50 value of ohmefentanyl stereoi somers in the naloxone-precipitated jumping test in mice. Morphine was used to assess the method and as a drug of comparison. The results indicate tha t the degree of physical dependence of morphine can been quantified by esti mating the ED50 value of morphine withdrawal jumping induced by naloxone. A significant difference was observed in withdrawal jumping ED50 values amon g ohmefentanyl stereoisomers. Of these isomers, F9202 and F9204 had similar ly potent analgesic action, but very significant difference in naloxone pre cipitated withdrawal response. Dependent potency index of F9204 was 618-fol d weaker than that of F9202. It is concluded that a stereo-structural diffe rence in physical dependence is found to exist among ohmefentanyl stereoiso mers. Compound F9204 displayed a strong analgesic action and weak physical dependent potency. (C) 2000 Elsevier Science Inc. All rights reserved.