Tacrine
(Synonyms: 他克林) 目录号 : GC64882
Tacrine is a centrally acting anticholinesterase and indirect cholinergic agonist. Tacrine hydrochloride hydrate is an inhibitor of both acetyl (AChE) and butyryl-cholinestrase (BChE) with IC50s of 31 nM and 25.6 nM, respectively.
Cas No.:321-64-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Tacrine is a centrally acting anticholinesterase and indirect cholinergic agonist. Tacrine hydrochloride hydrate is an inhibitor of both acetyl (AChE) and butyryl-cholinestrase (BChE) with IC50s of 31 nM and 25.6 nM, respectively.
Tacrine hydrochloride is an inhibitor of three different hepatic microsomal cytochrome P-450 enzyme sub-families. Tacrine hydrochloride at 40 mg/mL, 80 mg/mL or 200 mg/mL inhibits 3-hydroxymethyl antipyrine (HMA) production by 17%, 24% and 41% and OHA production by 52%, 55% and 79%, respectively, in hepatic microsome. [1] Tacrine severely inhibits normal levels of secretion of soluble APP derivatives by cells into conditioned media in glial, fibroblast, pheochromocytoma (PC12), and neuroblastoma cells. Tacrine treatment does not alter the level of HSP-70 in cell extracts and tacrine affected mildly the secretion of PN-1 in neuroblastoma and PC12 cells. [2] Tacrine (1 μM) attenuates the neurotoxic effect of A beta(25-35) in rat PC12 cells. [3]
Tacrine (3 mg/kg, i.p.) prevents the avoidance impairment induced by 5 mg/kg amitriptyline on shuttle-box avoidance acquisition as well as on a previously learned avoidance response in mice. [4] Tacrine (5mg/kg) shows significant effects of the inhibition of brain AChE for more than 6 hours in the rat hippocampus. Tacrine (5mg/kg) increases acetylcholine concentration in the synaptic cleft of the hippocampus mostly through AChE inhibition in the rat hippocampus, and the maximum increases are observed at about 1.5 hours. [5]
[1] Danbury TC, et al. Eur J Drug Metab Pharmacokinet, 1999, 24(1), 91-96. [2] Lahiri DK, et al. J Neurosci Res, 1994, 37(6), 777-787. [3] Svensson AL, et al. Neuroreport, 1998, 9(7), 1519-1522.
| Cas No. | 321-64-2 | SDF | Download SDF |
| 别名 | 他克林 | ||
| 分子式 | C13H14N2 | 分子量 | 198.26 |
| 溶解度 | 储存条件 | 4°C, away from moisture and light | |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 5.0439 mL | 25.2194 mL | 50.4388 mL |
| 5 mM | 1.0088 mL | 5.0439 mL | 10.0878 mL |
| 10 mM | 0.5044 mL | 2.5219 mL | 5.0439 mL |
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| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
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2.
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Tacrine-Based Hybrids: Past, Present, and Future
Int J Mol Sci 2023 Jan 15;24(2):1717.PMID:36675233DOI:10.3390/ijms24021717.
Alzheimer's disease (AD) is a neurodegenerative disorder which is characterized by β-amyloid (Aβ) aggregation, τ-hyperphosphorylation, and loss of cholinergic neurons. The other important hallmarks of AD are oxidative stress, metal dyshomeostasis, inflammation, and cell cycle dysregulation. Multiple therapeutic targets may be proposed for the development of anti-AD drugs, and the "one drug-multiple targets" strategy is of current interest. Tacrine (THA) was the first clinically approved cholinesterase (ChE) inhibitor, which was withdrawn due to high hepatotoxicity. However, its high potency in ChE inhibition, low molecular weight, and simple structure make THA a promising scaffold for developing multi-target agents. In this review, we summarized THA-based hybrids published from 2006 to 2022, thus providing an overview of strategies that have been used in drug design and approaches that have resulted in significant cognitive improvements and reduced hepatotoxicity.
Tacrine: In vivo veritas
Pharmacol Res 2017 Feb;116:29-31.PMID:28040533DOI:10.1016/j.phrs.2016.12.033.
Tacrine was initially synthesised in 1945 as part of a project seeking antibacterial drugs to treat infected wounds in soldiers. However, it was inactive in vitro against common strains of bacteria. Serendipitously, it was injected in vivo into dogs anaesthetised with chloroform and morphine and noted to immediately counter the respiratory rate depression caused by morphine but not block analgesia. Subsequent studies showed that Tacrine was an acetylcholinesterase inhibitor. When combined with morphine in ampoules it was possible to inject larger doses of morphine without causing respiratory depression and it was marketed for 10 years in Australia. Tacrine was also used alone for treating acute anticholinergic syndrome in the 1980s. Shortly after this, it was hypothesised by William Summers that it could be of benefit in treating the early stages of Alzheimer's dementia and an IND was granted by the US Food and Drug Administration and a use patent awarded to Summers. It was the first of four anticholinesterases to be approved for treating this condition although its variable pharmacokinetics was a disadvantage.
Therapeutic Potential of Multifunctional Tacrine Analogues
Curr Neuropharmacol 2019;17(5):472-490.PMID:29651948DOI:10.2174/1570159X16666180412091908.
Tacrine is a potent inhibitor of cholinesterases (acetylcholinesterase and butyrylcholinesterase) that shows limiting clinical application by liver toxicity. In spite of this, analogues of Tacrine are considered as a model inhibitor of cholinesterases in the therapy of Alzheimer's disease. The interest in these compounds is mainly related to a high variety of their structure and biological properties. In the present review, we have described the role of cholinergic transmission and treatment strategies in Alzheimer's disease as well as the synthesis and biological activity of several recently developed classes of multifunctional Tacrine analogues and hybrids, which consist of a new paradigm to treat Alzheimer's disease. We have also reported potential of these analogues in the treatment of Alzheimer's diseases in various experimental systems.
Tacrine, and Alzheimer's treatments
J Alzheimers Dis 2006;9(3 Suppl):439-45.PMID:16914883DOI:10.3233/jad-2006-9s350.
The story of the development of Tacrine began from its synthesis as an intravenous antiseptic in 1940 by Adrian Albert in Australia. In the 1970's William Summers began using Tacrine in treating drug overdose coma and delirium. He felt it might have application in Alzheimer's based on work done in England by Peter Davies. In 1981, Summers et al. gave intravenous Tacrine to Alzheimer's patients showed measurable improvement. Between 1981 and 1986, Summers worked with Art Kling and his group at UCLA to demonstrate usefulness of oral Tacrine in treatment of Alzheimer's patients. The average length of Tacrine use in 14 completing patients was 12.6 months and improvement was robust. This sparked controversy in the field. In 1993, after larger studies replicated the positive effect of Tacrine, it was approved by the US Food and Drug Administration for treatment of Alzheimer's disease.
[Tacrine and its derivatives in the therapy of Alzheimers disease]
Ceska Slov Farm 2012 Oct;61(5):210-21.PMID:23256654doi
Cholinesterase inhibitors have beneficial effects on the cognitive, functional, and behavioural symptoms of Alzheimers disease (AD). Up to date, they represent almost the only drugs approved by the U.S. Food and Drug Administration agency for AD treatment. The group involves donepezil, rivastigmine and galantamine. Apart from the above mentioned cholinesterase inhibitors, memantine is used for AD treatment as well acting as Nmethyl-D-aspartate (NMDA) non-competitive antagonist. Tacrine (9-amino-1,2,3,4-tetrahydroacridine) was the first cholinesterase inhibitor approved for symptomatic AD treatment. However, its several side effects (hepatotoxicity and gastrointestinal discomfort) limited Tacrine further use. Recently, novel Tacrine analogues are extensively investigated in endeavour to find less toxic compounds with the "multi-target directed ligand" profile affecting more AD pathological mechanisms. The following study summarizes the knowledge of up to date published Tacrine analogues, their structural aspects and biological properties. According to structural aspects, Tacrine derivatives are divided into three groups, where they are discussed.