Naloxegol (INN;PEGylated naloxol;[4] trade namesMovantik andMoventig) is aperipherally acting μ-opioid receptor antagonist developed byAstraZeneca, licensed fromNektar Therapeutics, for the treatment ofopioid-inducedconstipation.[5] It was approved in 2014 in adult patients with chronic, non-cancer pain.[6] Doses of 25 mg were found safe and well tolerated for 52 weeks.[7] When given concomitantly with opioid analgesics, naloxegol reduced constipation-related side effects, while maintaining comparable levels of analgesia.[8]
Naloxegol was previously aSchedule II drug in the United States because of its chemical similarity to noroxymorphone.[10] It was officially decontrolled in January 2015. It was reclassified as aprescription drug after theFDA andDEA concluded that theimpermeability of theblood–brain barrier to this compound made it non-habit-forming, and so without the potential forabuse.[11]
Chemically, naloxegol is apegylated (polyethylene glycol-modified)derivative of α-naloxol. Specifically, the 6-α-hydroxyl group of α-naloxol is connected via anether linkage to the freehydroxyl group of a monomethoxy-terminated n=7oligomer ofPEG, shown extending at the lower left of the molecule image at right. The "n=7" defines the number of two-carbon ethylenes, and so the chain length, of the attached PEG chain, and the "monomethoxy" indicates that the terminal hydroxyl group of the PEG is "capped" with amethyl group.[13] The pegylation of the 6-α-hydroxyl side chain ofnaloxol prevents the drug from crossing theblood–brain barrier (BBB).[8]
^Technically, the molecule that is attached via the ether link isO-methyl-heptaethylene glycol [that is, methoxyheptaethylene glycol, CH3OCH2CH2O(CH2CH2O)5CH2CH2OH], molecular weight 340.4,CAS number 4437-01-8. See"Compound Summary for CID 526555, Pubchem Compound 4437-01".PubChem Compound Database. Bethesda, MD:NCBI, U.S.NLM. 2016.Archived from the original on 5 February 2016. Retrieved28 January 2016.
