Binding affinities (pKi values) of medetomidine and ephedrine alkaloids on human α2A-, α2B-, and α2C-ARs in CHO cells
[3H]Rauwolscine was used as the radioligand in equilibrium competition radioligand binding assays for the α2A-, α2B-, and α2C-ARs, and nonspecific binding was measured in the presence of 10 μM phentolamine. pKi value = -log Ki (Ki was calculated according to the Cheng-Prusoff equation (Cheng and Prusoff, 1973) and the data are means ± S.E.M. of n = 6.
Compounds | pKi ± S.E.M. | ||||
|---|---|---|---|---|---|
| α2A-AR | α2B-AR | α2C-AR | |||
| Medetomidine | 6.15 ± 0.05 | 7.50 ± 0.03 | 7.65 ± 0.03 | ||
| 1R,2S-Ephedrine | 4.83 ± 0.16a | 4.78 ± 0.02 | 4.75 ± 0.12 | ||
| 1S,2R-Ephedrine | 4.44 ± 0.19a,b | 4.77 ± 0.05 | 4.65 ± 0.02 | ||
| 1R,2R-Pseudoephedrine | 4.95 ± 0.20c | 5.26 ± 0.08c | 4.88 ± 0.10c | ||
| 1S,2S-Pseudoephedrine | 4.19 ± 0.10c | 4.36 ± 0.10c | 4.18 ± 0.11c | ||
| 1R,2S-Norephedrine | 5.16 ± 0.05b | N.D. | 4.96 ± 0.20 | ||
| 1S,2S-Norpseudoephedrine | 4.32 ± 0.05 | N.D. | 4.50 ± 0.13 | ||
| 1R,2S-N-methylephedrine | 4.20 ± 0.30d | 4.29 ± 0.09d | 4.10 ± 0.30d | ||
N.D., not determined.
↵ a The mean pKi values for 1R,2S- and 1S,2R-ephedrine isomers were significantly different on the receptor subtype (P < 0.05 using the paired Student's t test).
↵ b The mean pKi values for 1R,2S-ephedrine and 1R,2S-norephedrine were significantly different on the receptor subtype (P < 0.05 using the paired Student's t test).
↵ c The mean pKi values for 1R,2R- and 1S,2S-pseudoephedrine isomers were significantly different on the receptor subtype (P < 0.05 using the paired Student's t test).
↵ d The mean pKi value for 1R,2S-N-methylephedrine was significantly different from the mean values of 1R,2S-ephedrine and 1R,2S-norephedrine on the receptor subtype (P < 0.05 using the paired Student's t test).