Latrepirdine is an orally active,and neuroactive antagonist of multiple drug targets, including histamine receptors, GluR, and 5-HT receptors, used as an antihistamine drug.
Latrepirdine 2HCl/拉曲吡啶二盐酸盐 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Mouse N2a neuroblastoma cells
500 pM-5 μM
6 h
To evaluate the effect of Latrepirdine on extracellular Aβ levels. Results showed that Latrepirdine at 500 nM significantly increased extracellular Aβ levels by 64% (p = 0.01).
Mol Neurodegener. 2009 Dec 17;4:51.
ATG5−/− MEFs
50 μM
3 h
No change in APP-CTF or p62 accumulation, confirming that the latrepirdine-related stimulation of clearance of APP metabolites and p62 was Atg5-dependent.
Mol Psychiatry. 2013 Aug;18(8):889-97.
WT MEFs
50 μM
3 h
Significant decreases in p62 and p-S6K levels, indicating enhanced autophagic activity.
Mol Psychiatry. 2013 Aug;18(8):889-97.
N2a neuroblastoma cells
500 nM or 50 μM
3 or 6 h
Significant and dose-dependent increase in LC3-II levels, indicating enhanced autophagosome formation and activity.
Mol Psychiatry. 2013 Aug;18(8):889-97.
HeLa cells
50 μM
6 h
Enhanced the number of eGFP-LC3 punctae, indicating that latrepirdine induced formation of autophagosomes.
Mol Psychiatry. 2013 Aug;18(8):889-97.
Yeast strain 2XαSyn
100 μM
Protected yeast from α-synuclein toxicity by inducing autophagy
Mol Psychiatry. 2013 Aug;18(8):882-8.
SH-SY5Y neurons
10 nM
14 days
Reduced levels of α-synuclein, including soluble and insoluble forms, promoting its degradation via autophagy
Mol Psychiatry. 2013 Aug;18(8):882-8.
cerebellar granule neurons (CGNs)
0.1 nM
24 h
To investigate the neuroprotective effects of Latrepirdine against glutamate excitotoxicity, results showed significant neuroprotection at 0.1 nM concentration.
Transl Psychiatry. 2013 Oct 22;3(10):e317.
Latrepirdine 2HCl/拉曲吡啶二盐酸盐 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Tg2576 mice
Transgenic mice overexpressing Swedish mutant APP
Intraperitoneal injection
3.5 mg/kg
Single injection, observed for 10 hours
To evaluate the effect of Latrepirdine on brain interstitial fluid Aβ levels. Results showed that a single injection of Latrepirdine significantly increased ISF Aβx-40 levels by 40% (p = 0.01).
Mol Neurodegener. 2009 Dec 17;4:51.
Mice
TgCRND8 transgenic mice
Intraperitoneal injection
3.5 mg/kg
Once daily for 31 days
Improved learning behavior and reduced accumulation of Aβ42 and α-synuclein.
Mol Psychiatry. 2013 Aug;18(8):889-97.
Wild-type mice
Wild-type mice
Intraperitoneal injection
3.5 mg/kg
Once daily for 21 days
Enhanced autophagy activity and reduced α-synuclein monomer levels in the brain
Mol Psychiatry. 2013 Aug;18(8):882-8.
Mice
FUS transgenic mouse model
Oral administration via drinking water
12 mg/kg/day
From the age of 42 days onwards
DF402 delayed the onset and slowed the progression of pathology, increasing animal lifespan by 13%.
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