OLINVO™ (oliceridine injection) was designed to have an improved analgesic profile by optimizing opioid receptor pharmacology, and has been granted Breakthrough Therapy designation by the FDA. OLINVO is the first μ-receptor G protein pathway selective modulator (μGPS), a biased ligand targeting the μ-opioid receptor. In preclinical studies, OLINVO activated the μ-opioid G protein receptor pathway in a manner similar to strong opioids such as morphine and fentanyl, and, like these drugs, OLINVO was a powerful analgesic. Unlike those drugs, in cell-based studies OLINVO did not engage the β-arrestin pathway, which was shown in other preclinical studies to inhibit morphine analgesia and promote morphine-induced constipation, respiratory depression, and analgesic tolerance.(1,2).
In preclinical studies, OLINVO was more potent than morphine, and it reached peak analgesia faster. OLINVO caused less gastrointestinal dysfunction than morphine at equivalent analgesic doses. OLINVO also showed an improved relationship between analgesia and respiratory depression risk compared to morphine(3,4).
1. Bohn, L, et al. Enhanced Morphine Analgesia in Mice Lacking β-Arrestin 2. Science 286: 2495-2498, 1999. View on PubMed.
2. Raehal, K, et al. Morphine Side Effects in β-Arrestin 2 Knockout Mice. J Pharm Exp Therap 314: 1195-1201, 2005. View PDF.
3. DeWire SM et al. A G protein-biased ligand at the mu opioid receptor is potently analgesic with reduced gastrointestinal and respiratory dysfunction compared with morphine. J Pharmacol Exp Ther. 2013 Mar;344(3):708‑17. View PDF.
4. Chen X.T. et al. Structure-Activity Relationships and Discovery of a G Protein Biased Mu Opioid Receptor Ligand, TRV130, for the Treatment of Acute Severe Pain. J. Med. Chem. 2013. View PDF.
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