MOVANTIK (naloxegol) is a peripherally-acting mu-opioid receptor antagonist indicated for the treatment of opioid-induced constipation (OIC) in adult patients with chronic noncancer pain. It is being investigated for the treatment of constipation as a side effect of prescription opioid pain medicines.

Diphenoxylate is an opioid drug used for the treatment of acute diarrhea. The drug is used in combination with atropine and marketed under names Lomotil and Diphenoxylate hydrochloride and atropine sulfate. Diphenoxylate is biotransformed in man by ester hydrolysis to diphenoxylic acid (difenoxine), which is biologically active and the major metabolite in the blood. The drug exerts its action by activating mu opioid receptors of intestinal mucosa.

Mirfentanil was developed as CNS analgesic with a short duration of action. It induced antinociception predominately through mu opioid receptors. It was shown that at doses larger than those, which exert opioid effects, mirfentanil had nonopioid analgesic effects. The drug was successfully encapsulated in liposomes having a variety of compositions. The lipid composition of the formulation was varied to optimize the stabilization of liposomes and the encapsulation of solutes. Mirfentanil participated in phase II clinical trials for the treatment of pain. However, this study was discontinued.

Cebranopadol is a novel analgesic nociceptin/orphanin FQ peptide (NOP) and opioid receptor agonist. Cebranopadol, by its combination of agonism at NOP and opioid receptors, affords highly potent and efficacious analgesia in various pain models with a favorable side effect profile. Cebranopadol displays analgesic, antiallodynic and antihyperalgesic properties in several rat models of acute nociceptive, inflammatory, cancer and neuropathic pain. Unlike morphine, cebranopadol did not disrupt motor coordination and respiration at doses within and exceeding the analgesic dose range possessing a broader therapeutic window than classical opioids. It is currently in clinical development for the treatment of severe chronic nociceptive and neuropathic pain.

Ocfentanil, a compound structurally similar to the opioid analgesic fentanyl, was developed in the early 1990’s with the hope that it would provide a better clinical safety profile than fentanyl. The receptor pharmacology of ocfentanil appears to share pharmacodynamic effects with fentanyl and other μ opioid agonists, including analgesia, sedation, and respiratory depression. In rodents, ocfentanil was approximately 2.5 times more potent as an analgesic than fentanyl and had a shorter duration of action. Because the preclinical research suggested that ocfentanil had a better safety profile than fentanyl, it was selected for clinical evaluation. Like other μ opioid agonists, ocfentanil has been reported to produce itching, nausea, sedation, and severe respiratory depression. Chest pain, psychosis, and agitation have also been reported. In humans, however, ocfentanil had a similar potency (3 ug/kg ocfentanil produced effects that were comparable to 5 ug/kg fentanyl) and side-effects profile as fentanyl so further clinical development was discontinued. Ocfentanil is not approved in any country for medical useand is under national control in Canada, the United Kingdom, and China.

Normorphine is an opiate analog, specifically the N-demethylated derivative of morphine. It was first described in the 1953 as part of an effort to characterize N-substituted morphine analogs. Normorphine has relatively little opioid activity, but it is a useful intermediate for the production of more potent morphine analogs. It is also a major metabolite of morphine.