LatrepirdineBrain cell death inhibitor CAS# 97657-92-6 |
2D Structure
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Quality Control & MSDS
3D structure
Package In Stock
Number of papers citing our products
Cas No. | 97657-92-6 | SDF | Download SDF |
PubChem ID | 23729232 | Appearance | Powder |
Formula | C21H27Cl2N3 | M.Wt | 392.37 |
Type of Compound | N/A | Storage | Desiccate at -20°C |
Synonyms | Dimebone, Latrepirdine | ||
Solubility | DMSO : 6.4 mg/mL (16.31 mM; Need warming) | ||
Chemical Name | 2,8-dimethyl-5-[2-(6-methylpyridin-3-yl)ethyl]-3,4-dihydro-1H-pyrido[4,3-b]indole;dihydrochloride | ||
SMILES | CC1=CC2=C(C=C1)N(C3=C2CN(CC3)C)CCC4=CN=C(C=C4)C.Cl.Cl | ||
Standard InChIKey | GTWLIQOLGOZTLF-UHFFFAOYSA-N | ||
Standard InChI | InChI=1S/C21H25N3.2ClH/c1-15-4-7-20-18(12-15)19-14-23(3)10-9-21(19)24(20)11-8-17-6-5-16(2)22-13-17;;/h4-7,12-13H,8-11,14H2,1-3H3;2*1H | ||
General tips | For obtaining a higher solubility , please warm the tube at 37 ℃ and shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months. We recommend that you prepare and use the solution on the same day. However, if the test schedule requires, the stock solutions can be prepared in advance, and the stock solution must be sealed and stored below -20℃. In general, the stock solution can be kept for several months. Before use, we recommend that you leave the vial at room temperature for at least an hour before opening it. |
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About Packaging | 1. The packaging of the product may be reversed during transportation, cause the high purity compounds to adhere to the neck or cap of the vial.Take the vail out of its packaging and shake gently until the compounds fall to the bottom of the vial. 2. For liquid products, please centrifuge at 500xg to gather the liquid to the bottom of the vial. 3. Try to avoid loss or contamination during the experiment. |
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Shipping Condition | Packaging according to customer requirements(5mg, 10mg, 20mg and more). Ship via FedEx, DHL, UPS, EMS or other couriers with RT, or blue ice upon request. |
Description | Non-selective antihistamine that displays cognitive enhancing abilities. Also displays high affinity for 5-HT (particularly 5-HT6 and 5-HT7), α-adrenergic, dopaminergic, AMPA and NMDA receptors, and L-type calcium channels. Does not inhibit acetylcholinesterase activity. Exhibits neuroprotective activity in cellular models of Alzheimer's and Huntington's disease and preserves cognitive function following administration to AF64A lesioned rats. Protects neurons against the neurotoxic action of β-amyloid fragment; shown to enhance autophagy in yeast and reduce intracellular Aβ42 levels. |
Latrepirdine Dilution Calculator
Latrepirdine Molarity Calculator
1 mg | 5 mg | 10 mg | 20 mg | 25 mg | |
1 mM | 2.5486 mL | 12.7431 mL | 25.4861 mL | 50.9723 mL | 63.7154 mL |
5 mM | 0.5097 mL | 2.5486 mL | 5.0972 mL | 10.1945 mL | 12.7431 mL |
10 mM | 0.2549 mL | 1.2743 mL | 2.5486 mL | 5.0972 mL | 6.3715 mL |
50 mM | 0.051 mL | 0.2549 mL | 0.5097 mL | 1.0194 mL | 1.2743 mL |
100 mM | 0.0255 mL | 0.1274 mL | 0.2549 mL | 0.5097 mL | 0.6372 mL |
* Note: If you are in the process of experiment, it's necessary to make the dilution ratios of the samples. The dilution data above is only for reference. Normally, it's can get a better solubility within lower of Concentrations. |
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Latrepirdine is an orally active, small molecule compound that has been shown to inhibit brain cell death in animal models of Alzheimer's disease and Huntington's disease. Research suggests it may also have cognition-enhancing effects in healthy individua
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Novel Sites of Neuroprotective Action of Dimebon (Latrepirdine).[Pubmed:26123670]
Mol Neurobiol. 2015 Oct;52(2):970-8.
Dimebon (Latrepirdine) is an anti-histaminergic agent which belongs to a fast-growing group of "old" medicines suggested to be of therapeutic utility for pathological conditions different from their original design ("repositioning"). Here, we overview the most recent studies on Dimebon directed to pathological processes in the brain-involving in vivo models of proteinopathies. In the latter, neurodegenerative effects are attributed to a group of aggregate-prone proteins such as gamma-synuclein, hyperphosphorylated tau, and fused in sarcoma (FUS), which are engaged in numerous neurological diseases. We also focus on in vitro models comprised of cultured SH-SY5Y neuroblastoma cells expressing mutant forms of transactive response DNA binding protein 43 kDa (TDP-43) and showing a reduced number of TDP-43 inclusion-containing cells upon Dimebon treatment along with activation of autophagy markers. Finally, we discuss Dimebon's action in improving cellular energy balance, stabilizing mitochondrial function by increasing the threshold for nonselective mitochondrial pore opening, as well as increasing the calcium retention capacity of mitochondria and reducing lipid peroxidation. Our results, together with data from other laboratories, warrant re-evaluation of the therapeutic potential of Dimebon and its newly designed analogs as promising disease-modifying agents to treat neurodegenerative disorders. Further, emerging data favor a possible anti-aging effect and application of Dimebon for the treatment of depression, anxiety, and ischemia. The most pronounced effect of Dimebon is observed when treatment starts early in disease onset. This is a major factor which needs to be taken into account when planning future clinical trials.
Minimization of CYP2D6 Polymorphic Differences and Improved Bioavailability via Transdermal Administration: Latrepirdine Example.[Pubmed:27072954]
Pharm Res. 2016 Aug;33(8):1873-80.
PURPOSE: Transdermal delivery has the potential to offer improved bioavailability by circumventing first-pass gut and hepatic metabolism. This study evaluated the pharmacokinetics of oral immediate release and transdermal Latrepirdine in extensive and poor CYP2D6 metabolizers (EM/PM). METHODS: Latrepirdine transdermal solution was prepared extemporaneously. The solution was applied with occlusive dressing to upper or middle back for 24 h. Each subject received a single dose of 8.14 mg oral, 5 mg transdermal, and 10 mg transdermal (EMs only) Latrepirdine free base in a fixed sequence. RESULTS: Twelve EMs and 7 PMs (50-79 years) enrolled and completed the study. Latrepirdine was well tolerated following both routes of administration. Dose-normalized Latrepirdine total exposures were approximately 11-fold and 1.5-fold higher in EMs and PMs, respectively following administration of transdermal relative to oral. Differences between EM and PM Latrepirdine exposures were decreased, with PMs having 1.9- and 2.7-fold higher peak and total exposures, respectively, following transdermal administration compared to 11- and 20-fold higher exposures, respectively, following oral administration. CONCLUSION: Transdermal delivery can potentially mitigate the large intersubject differences observed with compounds metabolized primarily by CYP2D6. Transdermal delivery was readily accomplished in the clinic using an extemporaneously prepared solution [NCT00990613].
Latrepirdine for Alzheimer's disease.[Pubmed:25897825]
Cochrane Database Syst Rev. 2015 Apr 21;(4):CD009524.
BACKGROUND: Current treatments for Alzheimer's disease (AD) provide modest symptomatic relief but do not slow the progression of the disease. Latrepirdine may modulate several targets involved in AD pathology, including lipid peroxidation, mitochondrial permeability, voltage-gated calcium ion channels as well as neurotransmitter receptor activity, and thus potentially represents both a symptomatic and disease-modifying intervention. Several randomized, placebo-controlled trials have sought to evaluate the effect of Latrepirdine on cognition, function and behaviour in patients with AD. OBJECTIVES: To evaluate the efficacy and safety of Latrepirdine for the treatment of AD. SEARCH METHODS: We searched the Specialized Register of the Cochrane Dementia and Cognitive Improvement Group on 4 June 2014 using the terms: Latrepirdine OR dimebon OR dimebolin OR 2,3,4,5-tetrahydro-2,8-dimethyl-5- (2-(6-methyl-3-pyridyl)ethyl)-1H-pyrido(4,3-b)indole. SELECTION CRITERIA: We included all randomized, double-blind, placebo-controlled trials where Latrepirdine was administered to patients with mild, moderate or severe AD. DATA COLLECTION AND ANALYSIS: We assessed the quality of studies and two authors extracted data. We calculated mean difference (MD), risk ratio (RR) and 95% confidence interval (CI) on an intention-to-treat (ITT) basis for all relevant outcome measures. MAIN RESULTS: Seven trials involving a total of 1697 participants were found and six were included in the quantitative analyses. No data were available from the seventh trial. Three trials involving 1243 patients were included in analyses of efficacy outcomes, and four trials involving 1034 patients were included in analyses of safety and tolerability outcomes. We judged five trials to be at high risk of bias due to selective outcome reporting and three to be at high risk of attrition bias. There was low quality evidence favouring Latrepirdine on the Clinician's Interview - Based Impression of Change Plus Caregiver Input after 26 weeks (CIBIC-Plus) (MD -0.60, 95% CI -0.89 to -0.31, 1 study, P < 0.001). Due to imprecision in the results, it was not possible to determine whether Latrepirdine had any effect on cognition measured with the Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-Cog) (MD -1.49, 95% CI -3.47 to 0.49, 3 studies, P = 0.14) or the Mini-Mental State Examination (MMSE) (MD 0.59, 95% CI -0.94 to 2.11, 3 studies, P = 0.45), or on function measured with the Alzheimer's Disease Co-operative Study - Activities of Daily Living scale (ADCS-ADL) (MD 1.00, 95% CI -1.15 to 3.15, 3 studies, P = 0.36) at study endpoint (26 or 52 weeks). We considered the evidence provided on these outcomes to be of overall low quality. However, there was some high quality evidence showing a very small benefit of Latrepirdine on the Neuropsychiatric Inventory (NPI) (MD -1.77, 95% CI -3.09 to -0.45, 3 studies, P = 0.009) at study endpoint (26 or 52 weeks). Additionally, moderate quality evidence suggested that Latrepirdine and placebo were comparable in adverse events (RR 1.03, 95% CI 0.93 to 1.14, P = 0.51), serious adverse events (RR 0.86, 95% CI 0.55 to 1.35, P = 0.52), dropouts (RR 0.91, 95% CI 0.65 to 1.27, P = 0.57) and dropouts due to adverse events (RR 0.98, 95% CI 0.57 to 1.67, P = 0.93). AUTHORS' CONCLUSIONS: Our meta-analysis is limited by the small number of studies, imprecision, inconsistencies between studies and likelihood of bias. Nevertheless, the evidence to date suggests that while not associated with an increased risk of adverse events compared with placebo, there is no effect of Latrepirdine on cognition and function in mild-to-moderate AD patients, though there appears to be a modest benefit for behaviour. Further studies should investigate the potential benefit of Latrepirdine on neuropsychiatric symptoms in AD.
The Effects of Latrepirdine on Amyloid-beta Aggregation and Toxicity.[Pubmed:26836170]
J Alzheimers Dis. 2016;50(3):895-905.
Latrepirdine (Dimebon) has been demonstrated to be a neuroprotective and cognition improving agent in neurodegenerative diseases that feature protein aggregation and deposition, such as Alzheimer's disease (AD). The accumulation of amyloid-beta (Abeta) protein aggregates is a key event in the neurodegenerative process in AD. This study explores if Latrepirdine modulation of protein aggregation contributes to its neuroprotective mechanism of action. Assessment of neuronal cell death showed that there was a significant reduction in lactate dehydrogenase release at an equimolar ratio of Abeta:Latrepirdine and with lower concentrations of Latrepirdine. The ability of Latrepirdine to alter the formation of Abeta42 aggregates was assessed by thioflavin-T fluorescence, western immunoblotting and atomic force microscopy (AFM). Despite showing a reduction in thioflavin-T fluorescence with Latrepirdine treatment, indicating a decrease in aggregation, immunoblotting and AFM showed a modest increase in both the formation and size of Abeta aggregates. The discrepancies between thioflavin-T and the other assays are consistent with previous evidence that cyclic molecules can interfere with thioflavin-T binding of amyloid protein preparations. The ability of Latrepirdine to modulate Abeta aggregation appears to be independent of its neuroprotective effects, and is unlikely to be a mechanism by which Latrepirdine offers protection. This study investigates the effect of Latrepirdine on Abeta aggregation, and presents evidence suggesting that caution should be applied in the use of thioflavin-T fluorescence based assays as a method for screening compounds for protein aggregation altering properties.
Latrepirdine (dimebon) enhances autophagy and reduces intracellular GFP-Abeta42 levels in yeast.[Pubmed:22903131]
J Alzheimers Dis. 2012;32(4):949-67.
Latrepirdine (Dimebon), an anti-histamine, has shown some benefits in trials of neurodegenerative diseases characterized by accumulation of aggregated or misfolded protein such as Alzheimer's disease (AD) and has been shown to promote the removal of alpha-synuclein protein aggregates in vivo. An important pathway for removal of aggregated or misfolded proteins is the autophagy-lysosomal pathway, which has been implicated in AD pathogenesis, and enhancing this pathway has been shown to have therapeutic potential in AD and other proteinopathies. Here we use a yeast model, Saccharomyces cerevisiae, to investigate whether Latrepirdine can enhance autophagy and reduce levels of amyloid-beta (Abeta)42 aggregates. Latrepirdine was shown to upregulate yeast vacuolar (lysosomal) activity and promote transport of the autophagic marker (Atg8) to the vacuole. Using an in vitro green fluorescent protein (GFP) tagged Abeta yeast expression system, we investigated whether Latrepirdine-enhanced autophagy was associated with a reduction in levels of intracellular GFP-Abeta42. GFP-Abeta42 was localized into punctate patterns compared to the diffuse cytosolic pattern of GFP and the GFP-Abeta42 (19:34), which does not aggregate. In the autophagy deficient mutant (Atg8Delta), GFP-Abeta42 showed a more diffuse cytosolic localization, reflecting the inability of this mutant to sequester GFP-Abeta42. Similar to rapamycin, we observed that Latrepirdine significantly reduced GFP-Abeta42 in wild-type compared to the Atg8Delta mutant. Further, Latrepirdine treatment attenuated Abeta42-induced toxicity in wild-type cells but not in the Atg8Delta mutant. Together, our findings provide evidence for a novel mechanism of action for Latrepirdine in inducing autophagy and reducing intracellular levels of GFP-Abeta42.
Dimebolin is a 5-HT6 antagonist with acute cognition enhancing activities.[Pubmed:19549510]
Biochem Pharmacol. 2009 Oct 15;78(8):1035-42.
Dimebolin (Dimebon), is a non-selective antihistamine approved in Russia for the treatment of allergy. Recently, this drug has been shown to be neuroprotective in cellular models of Alzheimer's disease and Huntington's disease, and to preserve cognitive function when chronically administered to AF64A lesioned rats. Interests in identifying the molecular targets of dimebolin have intensified with reports of efficacy in clinical trials with Alzheimer's patients. Dimebolin has been found to interact with a number of molecular targets including acetylcholinesterases, N-methyl-d-aspartate receptors, and voltage-gated calcium channels, with potencies in the range of 5-50 microM. In the present study, the action of dimebolin at the serotonin 5-HT(6) receptor was investigated. Dimebolin binds with moderate affinity to both the human and rat recombinant 5-HT(6) receptor (K(i)=26.0+/-2.5 nM and 119.0+/-14.0 nM respectively) as well as the native rat 5-HT(6) receptor, and acts as an antagonist in functional cAMP assays. Furthermore, dimebolin occupies the 5-HT(6) receptor in vivo as assessed by ex vivo autoradiography, with a dose-occupancy relationship similar to that of the selective 5-HT(6) antagonist SB-399885. Finally, both SB-399885 and dimebolin produce an acute enhancement of short-term social recognition memory, although dimebolin is approximately 10-fold less potent than SB-399885. Taken together, these studies demonstrate that dimebolin antagonizes the 5-HT(6) receptor with higher affinity than other targets characterized to date, and suggest that this activity may play a role in the acute cognition enhancing effects of this compound in preclinical models and in the clinic.
Antihistamine agent Dimebon as a novel neuroprotector and a cognition enhancer.[Pubmed:11462798]
Ann N Y Acad Sci. 2001 Jun;939:425-35.
Dimebon, launched earlier in Russia as an antihistamine drug, was evaluated as a representative of a new generation of anti-Alzheimer's drugs that have two beneficial actions: (1) to alleviate symptoms, and (2) to prevent progression of the disease. The drug demonstrated cognition and memory-enhancing properties in the active avoidance test in rats treated with the neurotoxin AF64A, which selectively destroys cholinergic neurons. Dimebon protected neurons in the cerebellum cell culture against the neurotoxic action of beta-amyloid fragment (A beta 25-35, EC50 = 25 microM). In vitro, Dimebon displayed Ca(2+)-blocking properties (IC50 = 57 microM, on isolated rat ileum intestine) and pronounced anticholinesterase activity (IC50 = 7.9 microM and 42 microM for butyrylcholine esterase and acetylcholine esterase, respectively). It also exhibited strong anti-NMDA activity in the prevention of NMDA-induced seizures in mice (EC50 = 42 +/- 6 mg/kg i.p.). A beneficial effect of Dimebon in the therapy of Alzheimer's disease was demonstrated in a pilot clinical trial performed in the Moscow Center of Gerontology. Fourteen patients who participated in the trial were evaluated for their state of personality and for the severity of the disease. The evaluation included orientation (space, place, time, and patient personality), memory for the past and present, life in present, speech, irritability, and so forth. During and after the eight-week therapy with Dimebon, cognitive and self-service functions of patients improved significantly, and psychopathic symptoms, anxiety, depression, tearfulness, and headache were substantially diminished. The results of these studies suggest Dimebon as a new candidate for the therapy of Alzheimer's-like disorders.