Donepezil, as a acetylcholinesterase (AChE) inhibitors, inhibits AChE activity thereby increasing the acetylcholine (ACh) levels. Pretreatment with donepezil suppressed the TNFα-induced sustained intracellular Ca2+ elevation in both rat HAPI and mouse primary microglial cells[3]. Exposure to donepezil resulted in a rapid and reversible block of Kv1.5 currents, with an IC50 value of 72.5 μM. Donepezil can directly block Kv1.5 channels in its open and closed states[4]. Donepezil itself enhances neurogenesis and improves cognitive function following TBI(Traumatic Brain Injury), even when injury-induced neurogenesis was inhibited[5].
Donepezil/多奈哌齐 细胞实验
Cell Line
Concentration
Treated Time
Description
References
OPC-DRG neuron co-culture
10 μM
9 days
Donepezil promotes myelination in OPC-DRG neuron co-culture.
Acta Pharmacol Sin. 2019 Nov;40(11):1386-1393.
Primary OPCs
2.5–20 μM
4 days
Donepezil significantly increases the percentage of MBP+ OLs generated from primary OPCs.
Acta Pharmacol Sin. 2019 Nov;40(11):1386-1393.
Mouse 6-3 microglial cells
5 μM
12 hours
Pretreatment with donepezil suppressed the TNFα-induced sustained intracellular Ca2+ elevation
J Neuroinflammation. 2017 Dec 22;14(1):258.
Mouse primary microglial cells
5 μM
12 hours
Pretreatment with donepezil suppressed the TNFα-induced sustained intracellular Ca2+ elevation
J Neuroinflammation. 2017 Dec 22;14(1):258.
Rat HAPI microglial cells
5 μM
12 hours
Pretreatment with donepezil suppressed the TNFα-induced sustained intracellular Ca2+ elevation
J Neuroinflammation. 2017 Dec 22;14(1):258.
APPsw-SY5Y cells
10 μmol/L
2 hours
To evaluate the inhibitory effect of donepezil on copper-induced Aβ1-42 production, results showed that donepezil significantly reduced Aβ1-42 production
Acta Pharmacol Sin. 2016 Nov;37(11):1401-1412.
Th17 cells
5 μM
48 hours
To evaluate the effect of Donepezil on Th17 cell differentiation. Results showed that Donepezil significantly reduced the expression of IL17A in Th17 cells and inhibited the activation of the JAK2-STAT3 signaling pathway.
Theranostics. 2023 Mar 21;13(6):1826-1842.
NPC-derived OPCs
20 μM
4.5 days
Donepezil significantly promotes OPC to OL differentiation, increasing the percentage of MBP+ cells.
Acta Pharmacol Sin. 2019 Nov;40(11):1386-1393.
Donepezil/多奈哌齐 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
Rat
Passive avoidance test model
Oral
0.1 mg/kg
Single dose
Evaluate the effect of Donepezil in the passive avoidance test model
Cell. 2021 Nov 24;184(24):5886-5901.e22
C57BL/6 mice
BLM-induced lung fibrosis mouse model
Intraperitoneal injection
1 mg/kg
Once daily for 21 days
To evaluate the effect of Donepezil on BLM-induced lung fibrosis and pulmonary hypertension. Results showed that Donepezil significantly improved pulmonary artery and RV remodeling, reduced lung fibrosis, and inhibited Th17 cell infiltration and activation.
Theranostics. 2023 Mar 21;13(6):1826-1842.
Male mice
VGLUT3T8I/T8I mutant mice
Intraperitoneal injection
0.3 mg/kg
Daily throughout the entire ABA paradigm
To evaluate the effect of donepezil on reversing the self-starvation phenotype in VGLUT3T8I/T8I mice, showing that donepezil effectively reversed the self-starvation behavior in mutant mice.
Nat Commun. 2024 Jul 7;15(1):5691
Mice
VAChTcKO mice
Intraperitoneal injection
0.3 mg/kg
Chronic treatment
Increasing cholinergic signaling by AChE inhibition was fully effective to treat the anorexia-like phenotype in VAChTcKO mice.
J Clin Invest. 2020 Dec 1;130(12):6616-6630
Mice
Scopolamine-induced memory-deficient mouse model
Intracalvariosseous administration
5 mg/kg
Single administration, lasting four weeks
To evaluate the long-term cognitive improvement effect of DPZ@LAM, results showed that a single ICO of DPZ@LAM significantly recovered cognitive function in scopolamine-induced memory-deficient mice, along with decreased acetylcholinesterase activity and increased brain-derived neurotrophic factor.
Theranostics. 2024 Oct 14;14(17):6708-6725
Mouse
Drd1a-tdTomato/Drd2-mVenus double transgenic mice
Subcutaneous injection
0.4 mg/kg
Single dose
To investigate the enhancement of aversive learning by donepezil through M1R-PKC-PAK signaling
Mol Psychiatry. 2022 Aug;27(8):3479-3492.
Mice
Chronic stress model
Intraperitoneal injection
1.0 mg/kg
Single administration
Investigated the effects of Donepezil on cognitive and emotional deficits in chronically stressed mice. Results showed Donepezil alone improved cognitive deficits but exacerbated anxiety-like behaviors, while combined with vHPC M1 receptor blockade rescued both phenotypes.
Sci Adv. 2024 Nov 8;10(45):eado1508
C57BL/6 mice
Cuprizone-induced demyelination model
Intraperitoneal injection
1.5 and 5 mg/kg
Daily for 1–3 weeks
Donepezil significantly promotes remyelination in vivo, reducing demyelination area and increasing myelin formation.
Acta Pharmacol Sin. 2019 Nov;40(11):1386-1393.
Mice
3xTg and 5xFAD mouse models
Intraperitoneal injection
1.0 and 2.0 mg/kg
Daily for 4 weeks
Low-dose donepezil significantly ameliorated MS-hTau-induced spatial memory deficits and reduced tau accumulation, with more prominent effects than high dose.
Clin Transl Med. 2021 Jun;11(6):e428
C57BL6/J mice
AlCl3-induced Alzheimer's disease model
Nasal administration
30 mg/kg
Once daily for 7 weeks
To evaluate the improvement of cognitive function and memory ability in AlCl3-induced AD mice by GH/CeO2NPs, results showed significant improvement.
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