Chemistry:PZM21
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| Formula | C19H27N3O2S |
| Molar mass | 361.50 g·mol−1 |
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PZM21 is an experimental opioid analgesic drug that is being researched for the treatment of pain.[1] It is claimed to be a functionally selective μ-opioid receptor agonist which produces μ-opioid receptor mediated G protein signaling, with potency and efficacy similar to morphine, but with less β-arrestin 2 recruitment.[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 tests on mice, PZM21 was slightly less potent than morphine or TRV130 as an analgesic, but also had significantly reduced adverse effects, with less constipation than morphine, and very little respiratory depression, even at high doses.[4] This research was described as a compelling example of how modern high-throughput screening techniques can be used to discover new chemotypes with specific activity profiles, even at targets such as the μ-opioid receptor which have already been thoroughly investigated.[5] More recent research has suggested however that at higher doses, PZM21 is capable of producing classic opioid side effects such as respiratory depression and development of tolerance and may have only limited functional selectivity.[6]
See also
References
- ↑ "Biasing Opioid Receptors and Cholesterol as a Player in Developmental Biology". Cell Chemical Biology 23 (9): 1039–1040. September 2016. doi:10.1016/j.chembiol.2016.09.007. PMID 27662248.
- ↑ "Structure-based discovery of opioid analgesics with reduced side effects". Nature 537 (7619): 185–190. September 2016. doi:10.1038/nature19112. PMID 27533032. Bibcode: 2016Natur.537..185M.
- ↑ "Low intrinsic efficacy for G protein activation can explain the improved side effect profiles of new opioid agonists". Science Signaling 13 (625): eaaz3140. March 2020. doi:10.1126/scisignal.aaz3140. PMID 32234959. https://nottingham-repository.worktribe.com/output/4193457.
- ↑ "Structure-based discovery of opioid analgesics with reduced side effects". Nature 537 (7619): 185–190. September 2016. doi:10.1038/nature19112. PMID 27533032. Bibcode: 2016Natur.537..185M.
- ↑ "Drug discovery: Designing the ideal opioid". Nature 537 (7619): 170–171. September 2016. doi:10.1038/nature19424. PMID 27533037. Bibcode: 2016Natur.537..170K.
- ↑ "The novel μ-opioid receptor agonist PZM21 depresses respiration and induces tolerance to antinociception". British Journal of Pharmacology 175 (13): 2653–2661. July 2018. doi:10.1111/bph.14224. PMID 29582414.
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