Oxilorphan (INN, USAN) (developmental code name L-BC-2605) is an opioid antagonist of the morphinan family that was never marketed.[1] It acts as a μ-opioid receptor (MOR) antagonist but a κ-opioid receptor (KOR) partial agonist, and has similar effects to naloxone and around the same potency as an MOR antagonist.[2] Oxilorphan has some weak partial agonist actions at the MOR (with miosis, nausea, dizziness, and some euphoria observed)[3][4] and can produce hallucinogenic/dissociative effects at sufficient doses, indicative of KOR activation.[5] It was trialed for the treatment of opioid addiction, but was not developed commercially.[6] The KOR agonist effects of oxilorphan are associated with dysphoria, which combined with its hallucinogenic effects, serve to limit its clinical usefulness; indeed, many patients who experienced these side effects refused to take additional doses in clinical trials.[7]
^Pircio AW, Gylys JA (April 1975). "Oxilorphan (l-N-cyclopropylmethyl-3,14-dihydroxymorphinan): a new synthetic narcotic antagonist". The Journal of Pharmacology and Experimental Therapeutics. 193 (1): 23–34. PMID237112.
^Sellers EM, Thakur R (April 1976). "Partial agonist properties and toxicity of oral oxilorphan". Journal of Clinical Pharmacology. 16 (4): 183–7. doi:10.1002/j.1552-4604.1976.tb01515.x. PMID4472. S2CID2819499.
^Gordon M (22 November 1974). "Abuse of CNS Agents". Annual Reports in Medicinal Chemistry. 9. Academic Press. pp. 41–. ISBN978-0-08-058353-2.
^Leander JD (January 1983). "Evidence that nalorphine, butorphanol and oxilorphan are partial agonists at a kappa-opioid receptor". European Journal of Pharmacology. 86 (3–4): 467–70. doi:10.1016/0014-2999(83)90198-x. PMID6131829.
^Tennant FS, Tate JA, Ruckel E (June 1976). "Clinical trial in post-addicts with oxilorphan (levo-BC-2605): a new narcotic antagonist". Drug and Alcohol Dependence. 1 (5): 329–37. doi:10.1016/0376-8716(76)90035-1. PMID13984.
^National Research Council (U.S.). Committee on Problems of Drug Dependence (1975). Problems of drug dependence. National Academy of Sciences. ISBN9780309024174.
Salvinorin A Also indirect D2 agonists, such as dopamine reuptake inhibitors (cocaine, methylphenidate), releasing agents (amphetamine, methamphetamine), and precursors (levodopa).