Internet Sales of "Research Grade Compounds": The Opioid SR-17018 (SR-17) as an Example

Several internet sites promote the sale of "research grade compounds." Although the purchaser attests that they are over 18 years of age, they know that the substances have not been approved by regulatory agencies and promise that they will not use them for human consumption, the compounds are supplied in tablet form, which is inconvenient for research use but very convenient for human consumption. One such compound is the opioid SR-17018 (aka "SR-17"). SR-17018 was originally synthesized at Scripps Research as part of a discovery effort to test whether a G-protein-'biased' mu-opioid receptor (MOR) agonist could separate the undesirable opioid effect of respiratory depression from the desirable effect of analgesia. It never progressed through the stages necessary for human clinical trials, so it remained a research "tool" drug. Regardless of the initial intent, the United States Drug Enforcement Agency (DEA) alerts that some "research grade compounds" such as SR-17018 are emerging as recreational or abused substances. If so, the absence of adequate human data creates a problem for healthcare providers who may encounter an overdose of such a compound without an adequate evidence base upon which to draw. This narrative review presents SR-17018 as a case study of the clinical uncertainty that a "research grade compound" introduces. It synthesizes in vitro, ex vivo, and plausible human pharmacology of SR-17018, and it presents an emergency department physician's experience with a suspected SR-17 overdose.