Carfentanil stabilizes µ opioid receptor conformations that are ultra-efficient in inhibiting cAMP, resistant to naloxone or nalmefene but sensitive to naltrexone

Adams AP, Pybus DA (1978) Delayed respiratory depression after use of fentanyl during anaesthesia. Br Med J 1(6108):278–279. https://doi.org/10.1136/bmj.1.6108.278

Article  PubMed  PubMed Central  CAS  Google Scholar 

Becker LD, Paulson BA, Miller RD, Severinghaus JW, Eger EI 2nd (1976) Biphasic respiratory depression after fentanyldroperidol or fentanyl alone used to supplement nitrous oxide anesthesia. Anesthesiology 44(4):291–296. https://doi.org/10.1097/00000542-197604000-00003

Article  PubMed  CAS  Google Scholar 

Blake AD, Bot G, Freeman JC, Reisine T (1997) Differential opioid agonist regulation of the mouse mu opioid receptor. J Biol Chem 272(2):782–790. https://doi.org/10.1074/jbc.272.2.782

Article  PubMed  CAS  Google Scholar 

Borden SA, Mercer SR, Saatchi A et al (2023) Carfentanil structural analogs found in street drugs by paper spray mass spectrometry and their characterization by high-resolution mass spectrometry. Drug Test Anal 15(5):484–494. https://doi.org/10.1002/dta.3431

Article  PubMed  CAS  Google Scholar 

Breit A, Lagace M, Bouvier M (2004) Hetero-oligomerization between beta2- and beta3-adrenergic receptors generates a beta-adrenergic signaling unit with distinct functional properties. J Biol Chem 279(27):28756–28765. https://doi.org/10.1074/jbc.M313310200

Article  PubMed  CAS  Google Scholar 

Chu J, Zheng H, Loh HH, Law PY (2008) Morphine-induced mu-opioid receptor rapid desensitization is independent of receptor phosphorylation and beta-arrestins. Cell Signal 20(9):1616–1624. https://doi.org/10.1016/j.cellsig.2008.05.004

Article  PubMed  PubMed Central  CAS  Google Scholar 

Costa EM, Hoffmann BB, Loew GH (1992) Opioid agonists binding and responses in SH-SY5Y cells. Life Sci 50(1):73–81. https://doi.org/10.1016/0024-3205(92)90199-y

Article  PubMed  CAS  Google Scholar 

Cowles CE Jr, Mitchell J, Stepp JE, Bewley VZ (2017) Carfentanil: a new and often unrecognized threat. J Spec Oper Med 17(3):120–122. https://doi.org/10.55460/8N90-FU1K

Article  PubMed  Google Scholar 

Delcher C, Wang Y, Vega RS et al (2020) Carfentanil Outbreak-Florida, 2016–2017. MMWR Morb Mortal Wkly Rep 69(5):125–129. https://doi.org/10.15585/mmwr.mm6905a2

Article  PubMed  PubMed Central  Google Scholar 

Doll C, Konietzko J, Poll F, Koch T, Hollt V, Schulz S (2011) Agonist-selective patterns of micro-opioid receptor phosphorylation revealed by phosphosite-specific antibodies. Br J Pharmacol 164(2):298–307. https://doi.org/10.1111/j.1476-5381.2011.01382.x

Article  PubMed  PubMed Central  CAS  Google Scholar 

Drummond GB, Davie IT, Scott DB (1977) Naloxone: dose-dependent antagonism of respiratory depression by fentanyl in anaesthetized patients. Br J Anaesth 49(2):151–154. https://doi.org/10.1093/bja/49.2.151

Article  PubMed  CAS  Google Scholar 

Faouzi A, Wang H, Zaidi SA et al (2023) Structure-based design of bitopic ligands for the micro-opioid receptor. Nature 613(7945):767–774. https://doi.org/10.1038/s41586-022-05588-y

Article  PubMed  CAS  Google Scholar 

Feasel MG, Moran TS, Cheng BC, Averick S (2024) Are carfentanil and acrylfentanyl naloxone resistant? Front Psychiatry 15:1359851. https://doi.org/10.3389/fpsyt.2024.1359851

Article  PubMed  PubMed Central  Google Scholar 

Fritzwanker S, Mouledous L, Mollereau C et al (2021) HA-MOP knockin mice express the canonical micro-opioid receptor but lack detectable splice variants. Commun Biol 4(1):1070. https://doi.org/10.1038/s42003-021-02580-6

Article  PubMed  PubMed Central  CAS  Google Scholar 

George AV, Lu JJ, Pisano MV, Metz J, Erickson TB (2010) Carfentanil–an ultra potent opioid. Am J Emerg Med 28(4):530–532. https://doi.org/10.1016/j.ajem.2010.03.003

Article  PubMed  Google Scholar 

Groer CE, Schmid CL, Jaeger AM, Bohn LM (2011) Agonist-directed interactions with specific beta-arrestins determine mu-opioid receptor trafficking, ubiquitination, and dephosphorylation. J Biol Chem 286(36):31731–31741. https://doi.org/10.1074/jbc.M111.248310

Article  PubMed  PubMed Central  CAS  Google Scholar 

Gustafsson M, Silva V, Valeiro C, Joaquim J, van Hunsel F, Matos C (2024) Misuse, abuse and medication errors’ adverse events associated with opioids—a systematic review. Pharmaceuticals (Basel) 17(8). https://doi.org/10.3390/ph17081009

Haigh JC, Lee LJ, Schweinsburg RE (1983) Immobilization of polar bears with carfentanil. J Wildl Dis 19(2):140–144. https://doi.org/10.7589/0090-3558-19.2.140

Article  PubMed  CAS  Google Scholar 

Harada H, Ueda H, Wada Y, Katada T, Ui M, Satoh M (1989) Phosphorylation of mu-opioid receptors—a putative mechanism of selective uncoupling of receptor–Gi interaction, measured with low-Km GTPase and nucleotide-sensitive agonist binding. Neurosci Lett 100(1–3):221–226. https://doi.org/10.1016/0304-3940(89)90688-5

Article  PubMed  CAS  Google Scholar 

Kazmi SM, Mishra RK (1986) Opioid receptors in human neuroblastoma SH-SY5Y cells: evidence for distinct morphine (mu) and enkephalin (delta) binding sites. Biochem Biophys Res Commun 137(2):813–820. https://doi.org/10.1016/0006-291x(86)91152-6

Article  PubMed  CAS  Google Scholar 

Kelly E, Bailey CP, Henderson G (2008) Agonist-selective mechanisms of GPCR desensitization. Br J Pharmacol 153 Suppl 1(Suppl 1):S379–88 https://doi.org/10.1038/sj.bjp.0707604

Kelly E, Conibear A, Henderson G (2023) Biased Agonism: lessons from studies of opioid receptor agonists. Annu Rev Pharmacol Toxicol 63:491–515. https://doi.org/10.1146/annurev-pharmtox-052120-091058

Article  PubMed  CAS  Google Scholar 

Khatoon H, Faudzi SMM (2024) Balancing acts: the dual faces of fentanyl in medicine and public health. Leg Med (Tokyo) 71:102507. https://doi.org/10.1016/j.legalmed.2024.102507

Article  PubMed  CAS  Google Scholar 

Kirchmayer U, Davoli M, Verster A (2000) Naltrexone maintenance treatment for opioid dependence. Cochrane Database Syst Rev(2):CD001333. https://doi.org/10.1002/14651858.CD001333

Kobilka BK (2007) G protein coupled receptor structure and activation. Biochim Biophys Acta 1768(4):794–807. https://doi.org/10.1016/j.bbamem.2006.10.021

Article  PubMed  CAS  Google Scholar 

Kolb P, Kenakin T, Alexander SPH et al (2022) Community guidelines for GPCR ligand bias: IUPHAR review 32. Br J Pharmacol 179(14):3651–3674. https://doi.org/10.1111/bph.15811

Article  PubMed  CAS  Google Scholar 

Krieter P, Gyaw S, Crystal R, Skolnick P (2019) Fighting fire with fire: development of intranasal nalmefene to treat synthetic opioid overdose. J Pharmacol Exp Ther 371(2):409–415. https://doi.org/10.1124/jpet.118.256115

Article  PubMed  PubMed Central  CAS  Google Scholar 

Langston JL, Moffett MC, Makar JR, Burgan BM, Myers TM (2020) Carfentanil toxicity in the African green monkey: therapeutic efficacy of naloxone. Toxicol Lett 325:34–42. https://doi.org/10.1016/j.toxlet.2020.02.008

Article  PubMed  CAS  Google Scholar 

Leen JLS, Juurlink DN (2019) Carfentanil: a narrative review of its pharmacology and public health concerns. Can J Anaesth 66(4):414–421. https://doi.org/10.1007/s12630-019-01294-y

Article  PubMed  CAS  Google Scholar 

Li Z, Pei Q, Cao L, Xu L, Zhang B, Liu S (2012) Propofol increases micro-opioid receptor expression in SH-SY5Y human neuroblastoma cells. Mol Med Rep 6(6):1333–1336. https://doi.org/10.3892/mmr.2012.1073

Article  PubMed  CAS 

Comments (0)

No login
gif