Uniform assessment and ranking of opioid Mu receptor binding constants for selected opioid drugs

The safe disposal of unused opioid drugs is an area of regulatory concern. While toilet flushing is recommended for some drugs to prevent accidental exposure, there is a need for data that can support a more consistent disposal policy based on an assessment of relative risk. For drugs acting at the Mu-opioid receptor (MOR), published measurements of binding affinity (Ki) are incomplete and inconsistent due to differences in methodology and assay system, leading to a wide range of values for the same drug thus precluding a simple and meaningful relative ranking of drug potency. Experiments were conducted to obtain Ki’s for 19 approved opioid drugs using a single binding assay in a cell membrane preparation expressing recombinant human MOR. The Ki values obtained ranged from 0.1380nM (sufentanil) to 12.486μM (tramadol). The drugs were separated into three categories based upon their Ki values: Ki>100nM (tramadol, codeine, meperidine, propoxyphene and pentazocine), Ki=1–100nM (hydrocodone, oxycodone, diphenoxylate, alfentanil, methadone, nalbuphine, fentanyl and morphine) and Ki