Carbamazepine is an orally active anticonvulsant known for its ability to block pressure-sensitive sodium ion channels, with an IC50 of 131 μM. It inhibits not only voltage-gated Na+, Ca2+, and K+ channels but also acts as an HDAC inhibitor with an IC50 of 2 μM. It is utilized in the research of epilepsy and neuropathic pain[1].[2].[3].
体内研究
In animal models, a dose of 250 mg/kg administered orally promotes liver regeneration and increases survival in mice undergoing partial hepatectomy (PHx)[6].
Additionally, Carbamazepine included in food at concentrations between 0.25% to 0.75% demonstrates mood-stabilizing effects in various mouse models, including ICR and C57BL/6 mice[7].
体外研究
In cellular studies, Carbamazepine at concentrations ranging from 0 to 500 μM over 10 days inhibits pre-adipocyte differentiation and reduces triglyceride accumulation over 7 days in cell lines such as 3T3-L1, 3T3-F442A, and T37i[4].
At concentrations between 5 to 20 μM, administered 15 minutes before exposure to lipopolysaccharide (LPS), it significantly reduces the production of nitric oxide (NO), inducible nitric oxide synthase (iNOS) protein, and phosphorylation of Akt in microglial (BV-2) cells[5].
Furthermore, at 20 μM, Carbamazepine inhibits LPS-induced expression of COX-2 and production of TNF-α in the same cells[5].
Carbamazepine/卡马西平 细胞实验
Cell Line
Concentration
Treated Time
Description
References
C1R-HLA-B*15:02 transfectants
25 μg/mL
48 hours
Co-culture experiments showed TCR immune response to carbamazepine
Nat Commun. 2019 Aug 8;10(1):3569.
HeLa cells
20 μM
24 hours
Reduced ER stress caused by N617K collagen X mutation, decreased intracellular mutant collagen X protein levels
J Clin Invest. 2017 Oct 2;127(10):3861-3865.
RAW 264.7 cells
50 μM
24 hours
Enhanced autophagic killing of intracellular mycobacteria
EMBO Mol Med. 2015 Feb;7(2):127-39.
Primary human macrophages
50 μM
24 hours
Enhanced autophagic killing of intracellular M. tuberculosis
EMBO Mol Med. 2015 Feb;7(2):127-39.
HEK293T cells
8-64 μM
24 hours
To assess the effects of carbamazepine on Wnt signaling, results showed that carbamazepine can partially suppress Wnt3a-induced luciferase activity
J Med Chem. 2020 Mar 26;63(6):3252-3260.
Hippocampal neurons
100 µM
24 hours
Induced autophagic flux and restored mitochondrial homeostasis
Cell Rep. 2016 Oct 18;17(4):1053-1070.
Carbamazepine/卡马西平 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
HLA-B*15:02 transgenic mice
SCAR model
Oral
328 mg/kg/day
Daily administration for 4 weeks
Induced multi-organ injuries and SCAR symptoms
Nat Commun. 2019 Aug 8;10(1):3569.
Mice
PRRT2-deficient mouse model
Intraperitoneal injection
15 mg/kg
Single dose
Carbamazepine significantly alleviated paroxysmal dyskinesia phenotypes in PRRT2-deficient mice
Cell Res. 2018 Jan;28(1):90-110
Mice
MCDS mouse model
Gavage
250 mg/kg body weight/day
1 to 3 weeks
Reduced ER stress, improved chondrocyte differentiation, increased bone growth rates, reduced skeletal dysplasia
J Clin Invest. 2017 Oct 2;127(10):3861-3865.
C57BL/6 mice
Clostridioides difficile infection (CDI) model
Oral gavage
50 mg/kg
Every other day for 2 weeks
To evaluate the effect of carbamazepine on CDI symptoms and lysosomal function. Results showed that carbamazepine alleviated TcdB-induced lysosomal dysfunction, inflammation, and histological damage.
Autophagy. 2022 Sep;18(9):2050-2067.
Zebrafish
PTZ-induced seizure model
Immersion
50 μg/mL and 100 μg/mL
20 minutes
To evaluate the anti-seizure effect of carbamazepine in the PTZ-induced zebrafish seizure model. Results showed that carbamazepine significantly inhibited seizures at doses of 50 μg/mL and 100 μg/mL.
J Adv Res. 2024 Oct;64:249-262.
Mice
Trigeminal neuralgia model
Oral
60 mg/kg
12-hour interval
Carbamazepine significantly decreased S1 synchronization and alleviated mechanical allodynia and facial grooming behavior
J Clin Invest. 2023 Mar 1;133(5):e166408
Mice
Infected with highly virulent MDR M. tuberculosis CSU87
Intraperitoneal injection
50 mg/kg
Once daily for 30 days
Reduced bacterial burden in lung and spleen, improved lung pathology and stimulated adaptive immunity
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