PZM21

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PZM21
PZM21.svg
PZM21.png
Identifiers
CAS Number
ChemSpider
Chemical and physical data
FormulaC19H27N3O2S
Molar mass361.50 g·mol−1
3D model (JSmol)

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. 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.[2] 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.[3] 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.[4]

See also[edit]

References[edit]

  1. ^ Kostic M (September 2016). "Biasing Opioid Receptors and Cholesterol as a Player in Developmental Biology". Cell Chem Biol. 23 (9): 1039–1040. doi:10.1016/j.chembiol.2016.09.007. PMID 27662248.
  2. ^ Manglik, Aashish; Lin, Henry; Aryal, Dipendra K.; McCorvy, John D.; Dengler, Daniela; Corder, Gregory; Levit, Anat; Kling, Ralf C.; Bernat, Viachaslau; Hübner, Harald; Huang, Xi-Ping; Sassano, Maria F.; Giguère, Patrick M.; Löber, Stefan; Da Duan; Scherrer, Grégory; Kobilka, Brian K.; Gmeiner, Peter; Roth, Bryan L.; Shoichet, Brian K. (2016). "Structure-based discovery of opioid analgesics with reduced side effects". Nature. 537: 185–190. doi:10.1038/nature19112. ISSN 1476-4687. PMC 5161585. PMID 27533032.
  3. ^ Kieffer BL (September 2016). "Drug discovery: Designing the ideal opioid". Nature. 537 (7619): 170–171. doi:10.1038/nature19424. PMID 27533037.
  4. ^ Hill R, Disney A, Conibear A, Sutcliffe K, Dewey W, Husbands S, Bailey C, Kelly E, Henderson G (July 2018). "The novel μ-opioid receptor agonist PZM21 depresses respiration and induces tolerance to antinociception". Br. J. Pharmacol. 175 (13): 2653–2661. doi:10.1111/bph.14224. PMC 6003631. PMID 29582414.