PRE-084 hydrochloride is a high affinity, selective σ1 agonist, has an IC50 of 44 nM in the sigma receptor assay.
PRE-084 HCl 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Jurkat human leukemic T cells
0.1 nM to 10 μM
120 min
To evaluate the binding ability of PRE-084 and Amylovis-201 to the σ1 receptor, PRE-084 showed inhibition of the σ1 receptor, while Amylovis-201 did not show any inhibition.
Acta Pharm Sin B. 2024 Oct;14(10):4345-4359.
Fibroblasts from WS patients
0.03 μM to 1 μM
PRE-084 restored calcium ion transfer from the ER to the cytosol or mitochondria and improved mitochondrial respiration.
Sci Transl Med. 2022 Feb 9;14(631):eabh3763.
NG-108 cells
0.03 μM to 1 μM
PRE-084 increased calcium ion transfer from the ER to the cytosol or mitochondria and improved mitochondrial function.
Sci Transl Med. 2022 Feb 9;14(631):eabh3763.
PC6.3 cells
0.3 µM
24 h
PRE084 increased cell survival and counteracted the deleterious effects caused by N-terminal mutant huntingtin proteins.
Cell Death Dis. 2013 May 23;4(5):e646.
PRE-084 HCl 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Mice
Amnesia models induced by CO exposure or trimethyltin intoxication
Subcutaneous or intraperitoneal injection
1 mg/kg
Single administration, 30 minutes before testing
To evaluate the ameliorating effects of σ receptor ligands on learning and memory impairments induced by CO or trimethyltin. Results showed that the selective σ1 receptor agonist PRE-084 and non-selective σ1/σ2 ligands DTG, BD1008, and haloperidol significantly reversed the spontaneous alternation deficits observed after CO exposure or trimethyltin intoxication.
Br J Pharmacol. 1999 May;127(2):335-42
Mice
Dizocilpine-induced learning deficit model
Oral
0.01 to 1 mg/kg
Single administration
To evaluate the alleviating effect of Amylovis-201 on Dizocilpine-induced learning deficits, Amylovis-201 significantly attenuated Dizocilpine-induced memory impairment, and this effect was blocked by the σ1 receptor antagonist NE-100.
Acta Pharm Sin B. 2024 Oct;14(10):4345-4359.
Mice
Wfs1ΔExon8 mice
Intraperitoneal injection
0.3 mg/kg
Single injection
PRE-084 improved learning and memory deficits and alleviated anxiety behavior in Wfs1ΔExon8 mice.
Sci Transl Med. 2022 Feb 9;14(631):eabh3763.
Zebrafish
TDP43G348C zebrafish model
Bath water administration
5 μM and 10 μM
24 hours
PRE-084 treatment ameliorated maximal mitochondrial respiration in the TDP43 context and enhanced ER stress response and antioxidant cascade through NRF2 signaling, alleviating TDP43 toxicity.
Redox Biol. 2022 Dec;58:102542
Rats
Myocardial ischemia/reperfusion model
Intraperitoneal injection
1 mg/kg
Single dose 1 hour before surgery
PRE-084 pretreatment significantly improved cardiac function, reduced myocardial apoptosis, and exerted cardioprotective effects by activating the Akt/eNOS pathway.
Chin Med J (Engl). 2018 Mar 5;131(5):539-543
Mice
Dicer conditional knockout mouse model
Intraperitoneal injection
1 mg/kg
Daily for 8 weeks
To evaluate the neuroprotective effects of PRE-084 in Dicer cKO mice, the results showed that PRE-084 significantly attenuated the loss of DA neurons and motor impairments.
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