Analgesic activity and selectivity for opioid receptors of enantiomers of ohmefentanyl.

IM: To study analgesic activity and selectivity for opioid receptor subtypes of 8 enantomers of ohmefentanyl (Ohm). METHODS: Analgesic activity was evaluated using the hot plate test in mice. Selectivity for opioid receptors was determined in binding assay and bioassay. RESULTS: Among the 8 enantiomers of Ohm, the most potent isomer was F 9204, (+) cis (3R,4S,2′S ) Ohm, with an analgesic ED 50 (ip) value of 1 1 (0 8-1 3) μg·kg -1 . These enantiomers selectively acted on μ opioid receptors. K i values (μ) of enantiomers F 9204 and F 9202, (-) cis (3R,4S,2 ′R) Ohm were 4 0±2 0 and 5±4 pmol·L -1 , respectively. Their K i(δ)/ K i(μ) ratios were 22 500 and 22 800 , respectively. On guinea pig ileum and mouse vas deferens F 9202, F 9204, F 9205, F 9206, F 9207 , and F 9208 exhibited very potent inhibitons, which were antagonized by naloxone. In rabbit vas deferens these enantiomers had no effect. CONCLUSION: Eight enantiomers of Ohm selectively acted on μ opioid receptors. F 9204 showed the strongest analgesic activity and the highest selectivity for μ opioid receptors.