Resolution in the receptor binding of putative μ and κ opiates

Conditions for the stereospecific binding of ³H-ethylketocyclazocine and ³H-etorphine were established in membranes from rat and pigeon brain. In displacing the specific binding of the radiolabeled ligands, putative μ and κ opiates displayed different sensitivity toward sodium. In membranes from both species, the ratio of the sodium responses exhibited by a given drug in displacing ³H-ethylketocyclazocine and ³H-etorphine, respectively, ("double sodium ratio" = DSR) distinguished between μ and κ opiates. Compounds characterized on the basis of their pharmacological effects as κ opiates had DSR values between 0.3 and 2.2, regardless of their nature as agonists or antagonists. In contrast, the DSR for μ opiates ranged from 3.4 to 11. In rat brain membranes, UM 1382 (U-50, 488, a compound with pronounced κ activity) exhibited a DSR of 0.3, while the corresponding value for morphine was 7.4. Dynorphin-(1-13) had a DSR of 1. Within each of the two groups, the simple sodium ratio continued to serve as an index for the agonist or antagonist property of the tested opiates.