The G Protein Signal-Biased Compound TRV130; Structures, Its Site of Action and Clinical Studies
| Autor: | Yui Kuroda, Akane Komatsu, Yusuke Mizobuchi, Yuriko Fujii, Kaori Ohshima, Kanako Miyano, Yasuhito Uezono, Miki Nonaka, Sei Manabe, Minoru Narita, Eiko Uezono |
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| Rok vydání: | 2020 |
| Předmět: |
G protein
medicine.drug_class Analgesic Oliceridine Thiophenes Pharmacology 030226 pharmacology & pharmacy 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Opioid receptor GTP-Binding Proteins Drug Discovery Medicine Humans Spiro Compounds Adverse effect Receptor business.industry General Medicine Clinical trial Analgesics Opioid chemistry Opioid business 030217 neurology & neurosurgery medicine.drug Signal Transduction |
| Zdroj: | Current topics in medicinal chemistry. 20(31) |
| ISSN: | 1873-4294 |
| Popis: | Opioid agonists elicit their analgesic action mainly via μ opioid receptors; however, their use is limited because of adverse events including constipation and respiratory depression. It has been shown that analgesic action is transduced by the G protein-mediated pathway whereas adverse events are by the β-arrestin-mediated pathway through μ opioid receptor signaling. The first new-generation opioid TRV130, which preferentially activates G protein- but not β-arrestin-mediated signal, was constructed and developed to reduce adverse events. TRV130 and other G protein-biased compounds tend to elicit desirable analgesic action with less adverse effects. In clinical trials, the intravenous TRV130 (oliceridine) was evaluated in Phase I, II and III clinical studies. Here we review the discovery and synthesis of TRV130, its main action as a novel analgesic having less adverse events, its up-to-date status in clinical trials, and additional concerns about TRV130 as demonstrated in the literature. |
| Databáze: | OpenAIRE |
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