| Bioactivity | PZM21 is a potent and selective μ opioid receptor agonist with an EC50 of 1.8 nM[1][2][3]. | ||||||||||||
| Target | EC50: 1.8 nM (μ opioid receptor) | ||||||||||||
| Invitro | PZM21 has no detectable κOR or nociceptin receptor agonist activity-it is actually an 18 nM κOR antagonist-while it is a 500-fold weaker δOR agonist, making it a selective μOR agonist. At hERG, PZM21 has an IC50 of between 2 and 4 μM, 500- to 1,000-fold weaker than its potency as a μOR agonist. Signalling by PZM21 and other μOR agonists appears to be mediated primarily by the heterotrimeric G protein Gi/o, as its effect on cAMP levels is eliminated by pertussis toxin and no activity is observed in a calcium release assay [1]. | ||||||||||||
| In Vivo | PZM21 is a potent Gi activator with exceptional selectivity for μOR and minimal β-arrestin-2 recruitment. PZM21 is efficacious for the affective component of analgesia versus the reflexive component and is devoid of respiratory depression in mice at equi-analgesic doses. PZM21 displays dose-dependent analgesia in a mouse hotplate assay, with a per cent maximal possible effect (% MPE) of 87% reached 15 min after administration of the highest dose of drug tested [1].PZM21 has a long-lasting analgesic effect on CNS mediated-pain responses, but does not cause respiratory depression and constipation, two key side effects of opioid agonists[2]. | ||||||||||||
| Name | PZM21 | ||||||||||||
| CAS | 1997387-43-5 | ||||||||||||
| Formula | C19H27N3O2S | ||||||||||||
| Molar Mass | 361.50 | ||||||||||||
| Appearance | Solid | ||||||||||||
| Transport | Room temperature in continental US; may vary elsewhere. | ||||||||||||
| Storage |
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| Reference | [1]. Manglik A, et al. Structure-based discovery of opioid analgesics with reduced side effects. Nature. 2016 Sep 8;537(7619):185-190. [2]. Kostic M, et al. Biasing Opioid Receptors and Cholesterol as a Player in Developmental Biology. [3]. Araldi D, et al. Mu-opioid Receptor (MOR) Biased Agonists Induce Biphasic Dose-dependent Hyperalgesia and Analgesia, and Hyperalgesic Priming in the Rat. Neuroscience. 2018 Oct 17;394:60-71. |