PZM21 is a potent and selective μ opioid receptor agonist with an EC50 of 1.8 nM.
PZM21 细胞实验
Cell Line
Concentration
Treated Time
Description
References
LAD2 human mast cells
0.1 to 10 µM
2 hours
Evaluate the effect of PZM21 on mast cell degranulation; results showed no significant effect
Anesthesiology. 2019 Jul;131(1):132-147
HEK 293 cells
1- 30000 nM
2 minutes (Gi activation) and 10 minutes (arrestin-3 translocation)
Measure the effects of PZM21 on Gi protein activation and arrestin-3 translocation in HEK 293 cells. Results showed PZM21 is a low efficacy agonist for both Gi activation and arrestin-3 translocation.
Br J Pharmacol. 2018 Jul;175(13):2653-2661
Mouse Embryonic Fibroblasts (MEFs)
0.03 to 30 µM
48 hours
Evaluate the effect of PZM21 on fibroblast proliferation; results showed no significant effect
Anesthesiology. 2019 Jul;131(1):132-147
PZM21 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Rhesus macaques
Acute thermal nociception and drug self-administration model
To evaluate the antinociceptive effects, drug self-administration behavior, and pruritic effects of PZM21. Results showed PZM21 had similar antinociceptive effects and abuse potential as oxycodone, and intrathecal administration induced significant itch scratching.
Br J Anaesth. 2020 Oct;125(4):596-604
Mice
C57BL/6J mice
Subcutaneous injection
10 mg/kg, 20 mg/kg, 40 mg/kg
Single administration
PZM21 displayed 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 (40 mg/kg). The highest dose of morphine tested plateaued at 92% after 30 min. Intriguingly, no analgesic effect was observed for PZM21 in the tail-flick assay. PZM21 solely confers analgesia to the affective component of pain, with minimal effect on the reflexive component. Additionally, PZM21 was devoid of both respiratory depression and morphine-like reinforcing activity in mice at equi-analgesic doses.
Nature. 2016 Sep 8;537(7619):185-190
Mice (C57BL and CD-1)
Awake, freely moving mice
Intraperitoneal (i.p.) and subcutaneous (s.c.) injection
10–80 mg/kg
Single dose or twice daily administration for 3-5 days
Evaluate the effects of PZM21 on respiration and antinociception. Results showed PZM21 dose-dependently depressed respiration, similar to morphine. Repeated administration induced tolerance to antinociception but not to respiratory depression.
Evaluate the analgesic effects of the compounds. Results showed that compounds 6a, 6f, 6h, and 6k exhibited analgesia rates exceeding 97% in the acetic acid-induced writhing model, compounds 6a, 6b, and 6h showed significant antinociceptive action in the hot-water tail withdrawal test, and compounds 6a, 6f, and 6h exhibited prolonged antinociceptive effects in the formalin-induced paw licking assay
Molecules. 2024 Jun 21;29(13):2961
ICR mice
Formalin injection nociception assay and writhing test
To evaluate the analgesic effects of PZM21 and its analogues, PZM21 showed 77.9% and 92.8% analgesia in the formalin injection assay at 20 mg/kg and 40 mg/kg, respectively.
Molecules. 2019 Jan 11;24(2):259
Mice and rats
Thermal antinociception tests, conditioned place preference test, locomotor sensitization test, precipitated withdrawal test, self-administration test
Intraperitoneal or intrathecal
20, 40, or 80 mg/kg (i.p.); 2.5, 5, or 7.5 μg (intrathecal)
Single or repeated administration, lasting from hours to days
PZM21 exhibited antinociceptive efficacy, without rewarding or reinforcing properties. However, repeated administration led to antinociceptive tolerance and naloxone-precipitated withdrawal symptoms. PZM21 also enhanced morphine-induced antinociception and attenuated the expression of morphine reward.
Br J Pharmacol. 2019 Dec;176(23):4434-4445
Adult male Hartley guinea pigs
Lumbar intrathecal catheter connected to osmotic pump model
Intrathecal infusion
28 nmol/hour
Continuous for 14 days
Evaluate the effect of PZM21 on spinal mass formation in vivo; results showed no mass formation
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