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


CONCLUSIONS
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.
Jin
W Q
WQ
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, China.
Wang
Z X
ZX
Chen
J
J
Chen
X J
XJ
Chi
Z Q
ZQ
D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D005260:Female; D005283:Fentanyl / Q000031:analogs & derivatives* / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D008297:Male; D051379:Mice; D009119:Muscle Contraction / Q000187:drug effects; D011817:Rabbits; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014649:Vas Deferens / Q000187:drug effects
D000700:Analgesics; D017450:Receptors, Opioid, mu; C037016:F 7302; D005283:Fentanyl