Analgesic activity and selectivity for opioid receptors of enantiomers of ohmefentanyl
Abstract
AIM: 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 ED50 (i.p.) value of 1.1 (0.8-1.3) micrograms.kg-1. These enantiomers selectively acted on mu opioid receptors. Ki values (mu) 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 Ki(delta)/Ki(mu) 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 mu opioid receptors. F-9204 showed the strongest analgesic activity and the highest selectivity for mu opioid receptors.
Keywords:
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 ED50 (i.p.) value of 1.1 (0.8-1.3) micrograms.kg-1. These enantiomers selectively acted on mu opioid receptors. Ki values (mu) 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 Ki(delta)/Ki(mu) 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 mu opioid receptors. F-9204 showed the strongest analgesic activity and the highest selectivity for mu opioid receptors.