PZM21

PZM21 is a potent and selective μ opioid receptor agonist with an EC₅₀ of 1.8 nM^[1][2][3]. IC50 & Target: EC50: 1.8 nM (μ opioid receptor)^[1] In Vitro: 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].