Tacrine hydrochloride hydrate
(Synonyms: 他克林盐酸盐水合物；他克林盐酸盐一水合物) 目录号 : GC37718
Tacrine (Tetrahydroaminacrine, Tetrahydroaminoacridine) is a centerally active cholinesterase inhibitor that has been used to counter the effects of muscle relaxants, as a respiratory stimulant, and in the treatment of Alzheimer's disease and other central nervous system disorders. It also acts as a histamine N-methyltransferase inhibitor.
Cas No.:206658-92-6
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
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- Purity: >99.50%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Tacrine (Tetrahydroaminacrine, Tetrahydroaminoacridine) is a centerally active cholinesterase inhibitor that has been used to counter the effects of muscle relaxants, as a respiratory stimulant, and in the treatment of Alzheimer's disease and other central nervous system disorders. It also acts as a histamine N-methyltransferase inhibitor.
Tacirne is an active cholinesterase inhibitor that blocks the degradation of cholinergic nerves in the cerebral cortex and hippocampus to increase cholinergic transmission. Tacrine induces hepatic damages in vitro. It can also induce oxidative stress and mitochondrial dysfunction. Tacrine treatment in HepG2 cells markedly inhibits the phosphorylation of GSK3β[1].
In rats, tacrine increased markers of liver damages (ALT and AST), degenerative region areas, and numbers of infiltrating inflammatory cells. Tacrine is known to induce hepatocyte necrosis and degeneration[1]. In the past, tacrine was used for the treatment of cognitive dysfunction during vascular dementia and Alzheimer disease. It is found to abolish lipopolysaccharide induced inflammation including IL-6 secretion in the central nervous system. Tacrine can aggravate the progress of tularemia in a mouse model--the effect would be beneficial in several pathologies such as neurodegenerative disorders; e.g. the positive effect of tacrine when used in therapy for Alzheimer's disease would be attributed to its anti-inflammatory action in addition to any improvement in cognitive functions[2].
[1] Park SM, et al. Biol Pharm Bull. 2015, 38(2):184-92. [2] Miroslav Pohanka, et al. Journal of Applied Biomedicine. 2013, 11(3)：187-193. [3] Cumming P, et al. Biochem Pharmacol. 1992, 44(5):989-92.
| Cas No. | 206658-92-6 | SDF | |
| 别名 | 他克林盐酸盐水合物；他克林盐酸盐一水合物 | ||
| Canonical SMILES | NC1=C(CCCC2)C2=NC3=CC=CC=C31.[H]Cl.O | ||
| 分子式 | C13H17ClN2O | 分子量 | 252.74 |
| 溶解度 | DMSO: 32 mg/mL (126.61 mM and warming) | 储存条件 | Store at -20°C |
| 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 | 3.9566 mL | 19.7832 mL | 39.5664 mL |
| 5 mM | 0.7913 mL | 3.9566 mL | 7.9133 mL |
| 10 mM | 0.3957 mL | 1.9783 mL | 3.9566 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 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 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Solid-state characterization of Tacrine hydrochloride
J Pharm Biomed Anal 2012 Apr 7;63:53-61.PMID:22326286DOI:10.1016/j.jpba.2011.12.023.
The present study deals with the physicochemical characterization of solid forms of Tacrine monohydrochloride (TCR), a centrally active reversible acetylcholinesterase inhibitor for treating the symptoms of mild to moderate Alzheimer's disease, obtained by recrystallization of hot saturated solutions from different solvents. Recrystallization of the commercially available hydrate, TCR·H₂O, from water, hydroalcoholic solutions with ethanol, n-propanol, methanol and isopropanol (1:1, v/v) and isopropanol/water (8:2, v/v) afforded a new dihydrate phase TCR·2H₂O form I. The TCR samples obtained by desolvation of TCR·H₂O and TCR·2H₂O show temperature and melting enthalpy values very similar, thus confirming the existence of a unique anhydrous crystalline phase. Exposure of anhydrous TCR powder samples under different atmospheric conditions at room temperature, resulted in rehydration to TCR·H₂O at 32% relative humidity (RH), whereas at 100% RH a new solid form of TCR·2H₂O (TCR·2H₂O form II), i.e. a polymorph of the dihydrate isolated by recrystallization, was obtained. Differential scanning calorimetry (DSC), simultaneous thermogravimetric analysis (TGA/DSC), and thermo optical analysis (TOA) with support from X-ray powder diffractometry (PXRD) and Fourier transform infrared spectroscopy (FT-IR), were used for the characterization of the isolated solid forms of TCR and monitoring the water uptake of anhydrous TCR.
Pharmacologic treatments of dementia
Med Clin North Am 2002 May;86(3):657-74.PMID:12171061DOI:10.1016/s0025-7125(02)00007-x.
The management of dementia patients encompasses pharmacologic, behavioral, and psychosocial intervention strategies. Before pharmacologic intervention is instituted, it is important that sources of excess disability and comorbidity be eliminated or reduced. Identification of comorbid medical and psychiatric conditions, such as depression and delirium, should be identified and appropriately treated. Providing caregivers with education, support, and practical advice is a critical component of the management of the demented patient. The current standard of care for pharmacologic management of the cognitive and functional disabilities of AD consists of the combination of a cholinesterase inhibitor and high-dose vitamin E. This standard is based on the results of large-scale, double-blind, placebo-controlled trials. Cholinesterase inhibitors are the only FDA-approved pharmacologic treatments for AD. Cholinesterase inhibitors have been shown to be effective in the treatment of the cognitive, behavioral, and functional deficits of AD. Large-scale placebo-controlled trials of Tacrine, donepezil, rivastigmine, and galantamine have demonstrated moderate benefits in patients with mild to moderate AD. Donepezil, rivastigmine, and galantamine are the first-line choices in the treatment of AD because of their lack of hepatotoxicity, ease of administration, few significant drug-drug interactions, and mild to moderate side effects. There are few contraindications to the use of cholinesterase inhibitors. Known hypersensitivity to a specific drug or its derivatives is the only true contraindication. Cautious administration of cholinesterase inhibitors is advised in patients who have a previous history of allergy or adverse reactions to prior cholinesterase inhibitors, severe liver disease, preexisting bradycardia, peptic ulcer disease, current alcoholism, asthma, or chronic obstructive pulmonary disease. Nausea, vomiting, diarrhea, and anorexia are the most common side effects of cholinesterase inhibitors. These gastrointestinal side effects can be minimized by gradual dose increases, administration with food, adequate hydration, and judicious use of an antiemetic. Vitamin E has been demonstrated to slow the progression of AD in several small and one large placebo-controlled trials. Because of its low cost and safety, it is recommended in addition to a cholinesterase inhibitor for the treatment of AD. There are no FDA-approved treatments for DLB and VaD. One small placebo-controlled trial demonstrated that rivastigmine may be effective in the treatment of DLB. More large-scale placebo-controlled trials are needed to confirm the results of this study. Treatment of VaD focuses on the control, identification, and management of cerebrovascular disease and vascular risk factors. Although there are no peer-reviewed reports on the efficacy of cholinesterase inhibitors for VaD or mixed AD/VaD, early reports suggest that these agents may also be effective for mixed AD/VaD. The indications for the use of cholinesterase inhibitor drugs are eventually likely to broaden to include DLB, mixed AD/VaD, and AD in its more advanced stages.
Microparticles based on chitosan/pectin polyelectrolyte complexes for nasal delivery of Tacrine hydrochloride
Drug Deliv Transl Res 2013 Feb;3(1):33-41.PMID:25787866DOI:10.1007/s13346-012-0086-y.
The aim of this study was the investigation of powder-based formulations for nasal administration of Tacrine hydrochloride. The anti-Alzheimer drug was encapsulated in mucoadhesive microparticles based on chitosan/pectin polyelectrolyte complexes. Microparticles were prepared by means of two different technological approaches (direct spray-drying and spray-drying followed by lyophilization) and analysed in terms of size, morphology and physico-chemical characteristics. Moreover, water uptake and mucoadhesion ability were evaluated as well as drug release and permeation behaviour. The results suggest that lyophilization favours the formation of small particle aggregates with a size of 10 μm, instead of single particles (size smaller than 5 μm) such as direct spray-drying. Particles obtained with the two loading methods present different functional properties according to the different physical state of the loaded drug and its possible interaction with chitosan/pectin complex. Moreover, the presence of different amount of chitosan and pectin in the complex influences their ability to hydrate, interact with mucin and favour drug permeation.
Tacrine accelerates spatial long-term memory via improving impaired neural oscillations and modulating GAD isomers including neuro-receptors in the hippocampus of APP/PS1 AD mice
Brain Res Bull 2020 Aug;161:166-176.PMID:32473192DOI:10.1016/j.brainresbull.2020.05.007.
Tacrine (Amino tetrahydroacridine hydrochloride hydrate) is a non-competitive and reversible inhibitor of acetylcholine esterase, and butylcholinesterase. Alzheimer's disease (AD) shows multiple types of pathological pathway in which cholinergic neuron deficiency is 95 % popular and the oldest pathological mechanism. However, the effect of Tacrine on the hippocampal dependent memory is not yet known. In this study, we did verify that Tacrine induced recovery of the specific pattern associated memory along with long-term memory through the improvement in the pattern of neural oscillation from deficits condition in the hippocampus of 6th month old AD mice. Our results showed that Tacrine improved the performance of Morris water maze related spatial cognitive functions, and enhanced LTP in AD-TAC mice. Furthermore, our results implied that Tacrine strongly improve the patterns of neural oscillations, and hippocampal synaptic plasticity in the 6th month old APP-PS1 double transgenic AD-TAC mice via changing the theta and alpha power spectra including with the improvement in theta, alpha and gamma synchronization. Moreover, Tacrine generated the improvement in the theta cross spectra, theta-gamma phase-phase synchronization and theta-gamma phase-amplitude coupling. Besides, the data represented that Tacrine accelerated the expression of NR2B, SYP and GAD65 while it caused deceleration on the expression of GAD67 neurotransmitter and Aβ. Thus, our results infer that Tacrine works as a strong causative agent for improving the specific pattern-associated spatial long-term memory in the AD mice without showing any side effect.
Long-lasting antiamnesic effect of a novel anticholinesterase inhibitor (MF268)
Pharmacol Biochem Behav 1998 Apr;59(4):897-901.PMID:9586846DOI:10.1016/s0091-3057(97)00526-1.
In the present study a short (120 min) and long-lasting (360 min) antagonism of scopolamine-induced amnesia in rats was investigated in an eight-arm radial maze, by (3a S, 8a R)-1,2,3,3a,8,8a-hexahydro-1,3a,8-trimethylpyrrolo[2,3-b]indol-5-o l[8-(cis2,6-dimethyl-morpholin-4-yl)octyl]-carbamate L-bitartrate hydrate (MF268), a new cholinesterase inhibitor. Upon completing the training session, the rats were orally administered increasing doses of MF268 (2, 3, 6, 7, and 8 mg/kg) 60 min prior to s.c. injection of scopolamine (0.25 mg/kg). Following a further 60 min the rat was placed in the maze. The reversal of scopolamine-induced impairment was characterized by an inverted U-shaped dose-response curve. A significant reduction in the number of errors, and time taken to complete the maze was observed with a dose of 6 mg/kg. The compound improved memory retention without affecting scopolamine-induced hypermotility. When the same dose was administered 360 min prior to the test a significant reduction in the number of amnesic animals was observed, whereas no cognitive improvement was detected when either 1-Benzil-4-[(5,6-dimethoxy-1-indanon)-2-yl]-methyl piperidine hydrochloride (E2020) (0.25 mg/kg) or Tacrine (0.5 mg/kg) were administered 360 min prior to the test. The kinetics of whole-brain cholinesterase confirmed the long-lasting activity for MF268. A clinical relevance for the use of MF268 in AD treatment is suggested.