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 0.1380 nM (sufentanil) to 12.486 μM (tramadol). The drugs were separated into three categories based upon their Ki values: Ki > 100 nM (tramadol, codeine, meperidine, propoxyphene and pentazocine), Ki = 1-100 nM (hydrocodone, oxycodone, diphenoxylate, alfentanil, methadone, nalbuphine, fentanyl and morphine) and Ki < 1 nM (butorphanol, levorphanol, oxymorphone, hydromorphone, buprenorphine and sufentanil). These data add to the understanding of the pharmacology of opioid drugs and support the development of a more consistent labeling policies regarding safe disposal.