Benztropine mesylate is a centrally acting anticholinergic agent for the treatment of Parkinson's disease. In a multiple sclerosis mouse model, benztropine mesylate induced the differentiation of oligodendrocytes through M1 and M3 muscarinic receptors and enhanced re-myelination. Benztropine mesylate also acts as an anti-histamine and a dopamine re-uptake inhibitor, and as an allosteric antagonist of the human D2 dopamine receptor. For 4T1-luc2 spheres, the IC50 value of benztropine mesylate was around 5 μM[3]. Benztropine (BZT) and its analogues inhibit dopamine uptake and bind with moderate to high affinity to the dopamine transporter (DAT). The BZT analogues showed a wide range of histamine H(1) receptor (Ki=16-37,600 nM) and DAT (Ki=8.5-6370 nM) binding affinities[4].
Benztropine mesylate/甲磺酸苯扎托品 细胞实验
Cell Line
Concentration
Treated Time
Description
References
Primary rat optic-nerve-derived progenitor cells (OPCs)
500 nM (EC50)
6 days
Induced differentiation of OPCs into mature oligodendrocytes, significantly increased MBP expression
Nature. 2013 Oct 17;502(7471):327-332.
COS7 cells
0.1 nM to 1,000,000 nM
5 minutes
Evaluate the inhibitory effect of compound 10a on dopamine uptake, showing a Ki value of 47 nM, which is >4 times more potent than cocaine (Ki=198 nM)
J Med Chem. 2017 Dec 28;60(24):10172-10187.
CHO-BC cells
44 ± 9 μM
Benztropine was identified as a competitive inhibitor of the B0AT1 transporter, showing high selectivity and blocking neutral amino acid uptake in mouse intestine.
Br J Pharmacol. 2017 Mar;174(6):468-482.
HCT116 cells
20 µM
72 h
To evaluate the effect of Benztropine on tumoroid formation in human colon cancer cells HCT116. Results showed that Benztropine significantly inhibited tumoroid growth and exerted cytotoxicity.
Cancers (Basel). 2020 Feb 24;12(2):523.
LuM1/m9 reporter cells
20 µM
72 h
To evaluate the effect of Benztropine on tumoroid formation, MMP9 promoter activity, and cancer cell survival. Results showed that Benztropine significantly inhibited tumoroid formation, MMP9 promoter activity, and cancer cell viability.
Cancers (Basel). 2020 Feb 24;12(2):523.
Primary rat oligodendrocyte progenitor cells (OPCs)
0.5 μM
4 days
Benztropine upregulated myelination-related gene expression and restored the α-synuclein-induced myelination deficit.
Benztropine restored the α-synuclein-induced myelination deficit.
Acta Neuropathol. 2016 Jul;132(1):59-75.
OPCs co-cultured with mouse embryonic-stem-cell-derived neurons
1.5 μM
6 days
Promoted OPC differentiation and myelination, increased the number of MBP-positive oligodendrocytes
Nature. 2013 Oct 17;502(7471):327-332.
N2a cells (mouse brain neuroblastoma)
7.5–30 μM
24 hours
To evaluate the effect of Benztropine on neuron-like cell viability and oxidative stress. Results showed that Benztropine reduced the cytotoxic effect of oxaliplatin on N2a cells, increased glutathione levels, and decreased reactive oxygen species production.
Acta Neuropathol Commun. 2019 Jan 18;7(1):9.
CT26 cells (mouse colon carcinoma)
7.5–30 μM
24 hours
To evaluate the effect of Benztropine on tumor cell viability and oxidative stress. Results showed that Benztropine potentiated the cytotoxic effect of oxaliplatin on CT26 cells, reduced glutathione levels, and increased reactive oxygen species production.
Acta Neuropathol Commun. 2019 Jan 18;7(1):9.
Benztropine mesylate/甲磺酸苯扎托品 动物实验
Species
Animal Model
Administration
Dosage
Frequency
Description
References
BALB/c mice
Tumor allograft model
Intraperitoneal injection
0.5 mg/mouse
Thrice a week for three weeks
To evaluate the effect of Benztropine on tumor growth, circulating tumor cells, and metastasis. Results showed that Benztropine significantly suppressed tumor growth, reduced the number of circulating tumor cells, and attenuated the rate of metastasis.
Cancers (Basel). 2020 Feb 24;12(2):523.
Mice
MBP29 transgenic mice
Intraperitoneal injection
2 mg/kg
Daily for 30 consecutive days
Benztropine ameliorated the myelin deficit in MBP29 mice and prevented neuronal cell loss.
Acta Neuropathol. 2016 Jul;132(1):59-75.
SJL/J mice
Experimental autoimmune encephalomyelitis (EAE) model
Intraperitoneal injection
10 mg/kg
Daily for 30 days
Significantly reduced clinical severity in the EAE model and promoted remyelination
Nature. 2013 Oct 17;502(7471):327-332.
BALB/cJRj mice
Acute and chronic oxaliplatin-induced peripheral neuropathy models
Intraperitoneal injection
10 mg/kg
Daily for 6–8 weeks
To evaluate the protective effect of Benztropine on oxaliplatin-induced peripheral neuropathy. Results showed that Benztropine significantly improved cold hyperalgesia, tactile and cold hypoesthesia, and prevented demyelination and axonal morphological changes in the sciatic nerve.
Acta Neuropathol Commun. 2019 Jan 18;7(1):9.
C57BL/6 mice
Experimental autoimmune encephalomyelitis (EAE) and cuprizone-induced demyelination model
Subcutaneous implantation of mini-osmotic pumps
18 µg/µl
14-day pumps (rate of infusion 0.25 µL/h, 100 µL total volume)
Combination of benztropine with tuftsin significantly improved pathological outcomes in both EAE and cuprizone models, including alleviating demyelination and promoting remyelination.
Front Immunol. 2018 Nov 28;9:2784
Mice
Spastic mouse model
Intraperitoneal injection
2mg/kg
Single injection
Increased muscle rigidity
Br J Pharmacol. 1982 Jan;75(1):23-35
Mice
C57BL/6J mice
Oral
1.25 mg/5 g chow
Once daily for 14 days
To evaluate the efficacy of benztropine in inhibiting SLC6A19, results showed that at a pharmacologically active dose, benztropine did not significantly inhibit SLC6A19.
United States, California
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Miami, Florida, United States, 33316
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Worcester, Massachusetts, United States, 01605
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Detroit, Michigan, United States, 48201
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Minneapolis, Minnesota, United States, 55454
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New York, New York, United States, 10032
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Butner, North Carolina, United States, 27509
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Dallas, Texas, United States, 75235
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