Misc What was your worst detox/withdrawal?

[Smyth2]

I remember a good study of ohemfentanyl isomers:

Guo, G. W.; He, Y.; Jin, W. Q.; Zou, Y.; Zhu, Y. C.; Chi, Z. Q. (June 2000). "Comparison of physical dependence of ohmefentanyl stereoisomers in mice". Life Sciences. 67 (2): 113–120. doi:10.1016/S0024-3205(00)00617-2.

Abstract
Stereo-structural difference of ohmefentanyl stereoisomers on analgesic action and receptor affinity
has been studied. To assess the difference of ohmefentanyl stereoisomers in physical dependence, the
potency of physical dependence was quantified by estimating the ED50 value of ohmefentanyl stereo-
isomers in the naloxone-precipitated jumping test in mice. Morphine was used to assess the method
and as a drug of comparison. The results indicate that the degree of physical dependence of morphine
can been quantified by estimating the ED50 value of morphine withdrawal jumping induced by nalox-
one. A significant difference was observed in withdrawal jumping ED50 values among ohmefentanyl
stereoisomers. Of these isomers, F9202 and F9204 had similarly potent analgesic action, but very sig-
nificant difference in naloxone precipitated withdrawal response. Dependent potency index of F9204
was 618-fold weaker than that of F9202. It is concluded that a stereo-structural difference in physical
dependence is found to exist among ohmefentanyl stereoisomers. Compound F9204 displayed a strong
analgesic action and weak physical dependent potency.

 

[3DQSAR]

https://sci-hub.st/10.1016/S0024-3205(00)00617-2

I think it worth noting that the conclusion is open to some interpretation - jumping is quite a crude way to assess severity of withdrawal. I'm also cautious to assign analgesic activity using animal models as these have proven pretty inaccurate when analgesic activity was tested in man.

I am curious as to why a compound assigned high analgesic activity but low physical dependence liability hasn't been tested for DOR and NOP affinity. (to the best of my knowledge) It may be the case that the isomers considered to have low physical dependence compared to analgesic activity is not due to MOP affinity alone.

I mean, you have to find some constructive criticism if you can. There is an email address so if all else fails, it's possible one could simply ask of assays for DOR and NOP activity were carried out. I mean, if it makes a safer analgesic, it's still a good thing.

Still, it's a brilliant series of papers. I'm always curious with Chinese papers as to where the funding comes from.