Oliceridine
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Trade names | Olinvo |
Other names | TRV-130 |
Routes of administration | Intravenous |
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Formula | C22H30N2O2S |
Molar mass | 386.55 g·mol−1 |
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Oliceridine (developmental code name TRV-130; tentative brand name Olinvo) is an opioid drug that is under evaluation in human clinical trials for the intravenous treatment of severe acute pain. It is a μ-opioid receptor biased agonist developed by Trevena. In cell-based (in vitro) research, oliceridine elicits robust G protein signaling, with potency and efficacy similar to that of morphine, but with less β-arrestin 2 recruitment and receptor internalization [2]. However, recent reports highlight that this might be due to its low intrinsic efficacy [3], rather than functional selectivity or 'G protein bias' as initially reported. In vivo, it may have fewer adverse effects (including respiratory depression and constipation) compared with morphine.[4][5][6] In general, in vitro potency does not guarantee any clinical relevance in humans.[7]
Society and culture
An FDA advisory committee voted against the approval of oliceridine in 2018, due to concerns that the benefit of the drug did not exceed the risk. The risks of oliceridine include prolongation of the QT interval on the ECG, and depression of the respiratory drive (which could cause a person to stop breathing).[8] As a result of the committee's vote, the FDA declined to approve oliceridine, citing safety concerns.[9]
Oliceridine is seeking approval again from the FDA. A decision is expected before August 8, 2020.
See also
References
- ^ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA. Retrieved 22 Oct 2023.
- ^ DeWire SM, Yamashita DS, Rominger DH, Liu G, Cowan CL, Graczyk TM, Chen XT, Pitis PM, Gotchev D, Yuan C, Koblish M, Lark MW, Violin JD (March 2013). "A G protein-biased ligand at the μ-opioid receptor is potently analgesic with reduced gastrointestinal and respiratory dysfunction compared with morphine". Journal of Pharmacology and Experimental Therapeutics. 344 (3): 708–17. doi:10.1124/jpet.112.201616. PMID 23300227.
- ^ Gillis, A; Gondin, AB; Kliewer, A; Sanchez, J; Lim, HD; Alamein, C; Manandhar, P; Santiago, M; Fritzwanker, S; Schmiedel, F; Katte, TA; Reekie, T; Grimsey, NL; Kassiou, M; Kellam, B; Krasel, C; Halls, ML; Connor, M; Lane, JR; Schulz, S; Christie, MJ; Canals, M (31 March 2020). "Low intrinsic efficacy for G protein activation can explain the improved side effect profiles of new opioid agonists". Science signaling. 13 (625). doi:10.1126/scisignal.aaz3140. PMID 32234959.
- ^ "Structure-Activity Relationships and Discovery of a G Protein Biased μ Opioid Receptor Ligand, [(3-Methoxythiophen-2-yl)methyl]({2-[(9R)-9-(pyridin-2-yl)-6-oxaspiro-[4.5]decan-9-yl]ethyl})amine (TRV130), for the Treatment of Acute Severe Pain". Journal of Medicinal Chemistry. 56 (20): 8019–31. October 2013. doi:10.1021/jm4010829. PMID 24063433.
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ignored (help) - ^ Soergel DG, Subach RA, Sadler B, Connell J, Marion AS, Cowan C, Violin JD, Lark MW (October 2013). "First clinical experience with TRV130: Pharmacokinetics and pharmacodynamics in healthy volunteers". The Journal of Clinical Pharmacology. 54 (3): 351–7. doi:10.1002/jcph.207. PMID 24122908.
- ^ Staff (1 October 2015). "Acute Postoperative Pain". Genetic Engineering & Biotechnology News (Paper). 35 (17): 40.
- ^ Waldman, SA (July 2002). "Does potency predict clinical efficacy? Illustration through an antihistamine model". Annals of Allergy, Asthma & Immunology. 89 (1): 7–11, quiz 11-2, 77. doi:10.1016/S1081-1206(10)61904-7. PMID 12141724.
- ^ "FDA Panel Votes Against Analgesic Oliceridine". www.medpagetoday.com. MedPage Today, LLC. 11 October 2018. Retrieved 23 December 2018.
- ^ "FDA rejects Trevena's painkiller oliceridine | FierceBiotech". www.fiercebiotech.com. Questex LLC. Retrieved 23 December 2018.
External links