Latrepirdine | CAS#3613-73-8 | β-amyloid inhibitor

MedKoo Cat#: 598435 | Name: Latrepirdine

Description:

WARNING: This product is for research use only, not for human or veterinary use.

Latrepirdine (also known as Dimebon) is a small-molecule antihistamine that was initially developed in Russia and later investigated for neurodegenerative diseases. It exhibits moderate affinity for multiple CNS targets, including histamine H1 receptors (Ki ≈ 3–5 nM), serotonin receptors such as 5-HT6 (Ki ≈ 16–70 nM), and α-adrenergic and muscarinic receptors, contributing to its cognitive-enhancing effects. Latrepirdine has also been reported to inhibit NMDA receptors and block mitochondrial permeability transition pores, thereby reducing oxidative stress and preserving mitochondrial function in neurons. In preclinical studies, it demonstrated neuroprotective and procognitive effects in rodent models of Alzheimer's and Huntington's diseases.

Chemical Structure

Latrepirdine

CAS#3613-73-8 (free base)

Theoretical Analysis

MedKoo Cat#: 598435

Name: Latrepirdine

CAS#: 3613-73-8 (free base)

Chemical Formula: C21H25N3

Exact Mass: 319.2048

Molecular Weight: 319.45

Elemental Analysis: C, 78.96; H, 7.89; N, 13.15

Price and Availability

Size	Price	Availability
100mg	USD 750.00	2 Weeks
200mg	USD 1,250.00	2 Weeks
500mg	USD 2,650.00	2 Weeks
1g	USD 4,450.00	2 Weeks
2g	USD 6,450.00	2 Weeks

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Related CAS #

3613-73-8 (free base) 97657-92-6 (HCl)

Synonym

Latrepirdine; Dimebon; Dimeboline; Dimebolin; Preparation 84;

IUPAC/Chemical Name

2,8-dimethyl-5-(2-(6-methylpyridin-3-yl)ethyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole

InChi Key

JNODQFNWMXFMEV-UHFFFAOYSA-N

InChi Code

InChI=1S/C21H25N3/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

SMILES Code

CC1=CC=C(CCN2C3=C(CN(C)CC3)C4=C2C=CC(C)=C4)C=N1

Appearance

Solid powder

Purity

>98% (or refer to the Certificate of Analysis)

Shipping Condition

Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition

Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility

Soluble in DMSO

Shelf Life

>3 years if stored properly

Drug Formulation

This drug may be formulated in DMSO

Stock Solution Storage

0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code

2934.99.03.00

More Info

Product Data

Product Data

Instruction

View handling instruction

Biological target:

Latrepirdine is an orally-available drug, approved in Russia for use as a non-selective antihistamine, that has shown promise in the treatment of neurodegenerative diseases, including Alzheimer’s and Huntington’s disease.

In vitro activity:

The ability of latrepirdine to alter the formation of Aβ42 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 Aβ aggregates. The ability of latrepirdine to modulate Aβ aggregation appears to be independent of its neuroprotective effects, and is unlikely to be a mechanism by which latrepirdine offers protection. Reference: J Alzheimers Dis. 2016;50(3):895-905. https://pubmed.ncbi.nlm.nih.gov/26836170/

In vivo activity:

Treatment with latrepirdine increased AMPK activity in primary mouse motor neuron cultures and in SOD1(G93A) lumbar spinal cords. Mice "preconditioned" with latrepirdine showed a delayed symptom onset and a significant increase in life span (p < 0.01). Reference: Neurobiol Aging. 2015 Feb;36(2):1140-50. https://pubmed.ncbi.nlm.nih.gov/25443289/

Preparing Stock Solutions

The following data is based on the product molecular weight 319.45 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Concentration / Solvent Volume / Mass	1 mg	5 mg	10 mg
1 mM	1.15 mL	5.76 mL	11.51 mL
5 mM	0.23 mL	1.15 mL	2.3 mL
10 mM	0.12 mL	0.58 mL	1.15 mL
50 mM	0.02 mL	0.12 mL	0.23 mL

Formulation protocol:

1. Porter T, Bharadwaj P, Groth D, Paxman A, Laws SM, Martins RN, Verdile G. The Effects of Latrepirdine on Amyloid-β Aggregation and Toxicity. J Alzheimers Dis. 2016;50(3):895-905. doi: 10.3233/JAD-150790. PMID: 26836170; PMCID: PMC4927897. 2. Weisová P, Alvarez SP, Kilbride SM, Anilkumar U, Baumann B, Jordán J, Bernas T, Huber HJ, Düssmann H, Prehn JH. Latrepirdine is a potent activator of AMP-activated protein kinase and reduces neuronal excitability. Transl Psychiatry. 2013 Oct 22;3(10):e317. doi: 10.1038/tp.2013.92. PMID: 24150226; PMCID: PMC3818013. 3. Coughlan KS, Mitchem MR, Hogg MC, Prehn JH. "Preconditioning" with latrepirdine, an adenosine 5'-monophosphate-activated protein kinase activator, delays amyotrophic lateral sclerosis progression in SOD1(G93A) mice. Neurobiol Aging. 2015 Feb;36(2):1140-50. doi: 10.1016/j.neurobiolaging.2014.09.022. Epub 2014 Sep 26. PMID: 25443289. 4. Steele JW, Gandy S. Latrepirdine (Dimebon®), a potential Alzheimer therapeutic, regulates autophagy and neuropathology in an Alzheimer mouse model. Autophagy. 2013 Apr;9(4):617-8. doi: 10.4161/auto.23487. Epub 2013 Feb 4. PMID: 23380933; PMCID: PMC3627679.

In vitro protocol:

In vivo protocol:

1. Coughlan KS, Mitchem MR, Hogg MC, Prehn JH. "Preconditioning" with latrepirdine, an adenosine 5'-monophosphate-activated protein kinase activator, delays amyotrophic lateral sclerosis progression in SOD1(G93A) mice. Neurobiol Aging. 2015 Feb;36(2):1140-50. doi: 10.1016/j.neurobiolaging.2014.09.022. Epub 2014 Sep 26. PMID: 25443289. 2. Steele JW, Gandy S. Latrepirdine (Dimebon®), a potential Alzheimer therapeutic, regulates autophagy and neuropathology in an Alzheimer mouse model. Autophagy. 2013 Apr;9(4):617-8. doi: 10.4161/auto.23487. Epub 2013 Feb 4. PMID: 23380933; PMCID: PMC3627679.

1: Chau S, Herrmann N, Ruthirakuhan MT, Chen JJ, Lanctôt KL. Latrepirdine for Alzheimer's disease. Cochrane Database Syst Rev. 2015 Apr 21;(4):CD009524. doi: 10.1002/14651858.CD009524.pub2. Review. PubMed PMID: 25897825. 2: Cano-Cuenca N, Solís-García del Pozo J, Jordán J. [Latrepirdine: a systematic review of the preclinical studies]. Rev Neurol. 2015 Jan 1;60(1):35-42. Review. Spanish. PubMed PMID: 25522862. 3: Bharadwaj PR, Bates KA, Porter T, Teimouri E, Perry G, Steele JW, Gandy S, Groth D, Martins RN, Verdile G. Latrepirdine: molecular mechanisms underlying potential therapeutic roles in Alzheimer's and other neurodegenerative diseases. Transl Psychiatry. 2013 Dec 3;3:e332. doi: 10.1038/tp.2013.97. Review. PubMed PMID: 24301650; PubMed Central PMCID: PMC4030329. 4: Porter T, Bharadwaj P, Groth D, Paxman A, Laws SM, Martins RN, Verdile G. The Effects of Latrepirdine on Amyloid-β Aggregation and Toxicity. J Alzheimers Dis. 2016;50(3):895-905. doi: 10.3233/JAD-150790. PubMed PMID: 26836170; PubMed Central PMCID: PMC4927897. 5: Weisová P, Alvarez SP, Kilbride SM, Anilkumar U, Baumann B, Jordán J, Bernas T, Huber HJ, Düssmann H, Prehn JH. Latrepirdine is a potent activator of AMP-activated protein kinase and reduces neuronal excitability. Transl Psychiatry. 2013 Oct 22;3:e317. doi: 10.1038/tp.2013.92. PubMed PMID: 24150226; PubMed Central PMCID: PMC3818013. 6: HORIZON Investigators of the Huntington Study Group and European Huntington's Disease Network. A randomized, double-blind, placebo-controlled study of latrepirdine in patients with mild to moderate Huntington disease. JAMA Neurol. 2013 Jan;70(1):25-33. doi: 10.1001/2013.jamaneurol.382. PubMed PMID: 23108692. 7: Cano-Cuenca N, Solís-García del Pozo JE, Jordán J. Evidence for the efficacy of latrepirdine (Dimebon) treatment for improvement of cognitive function: a meta-analysis. J Alzheimers Dis. 2014;38(1):155-64. doi: 10.3233/JAD-130872. PubMed PMID: 23948924. 8: Coughlan KS, Mitchem MR, Hogg MC, Prehn JH. "Preconditioning" with latrepirdine, an adenosine 5'-monophosphate-activated protein kinase activator, delays amyotrophic lateral sclerosis progression in SOD1(G93A) mice. Neurobiol Aging. 2015 Feb;36(2):1140-50. doi: 10.1016/j.neurobiolaging.2014.09.022. Epub 2014 Sep 26. PubMed PMID: 25443289. 9: Ustyugov A, Shevtsova E, Bachurin S. Novel Sites of Neuroprotective Action of Dimebon (Latrepirdine). Mol Neurobiol. 2015 Oct;52(2):970-8. doi: 10.1007/s12035-015-9249-4. Epub 2015 Jun 30. Review. PubMed PMID: 26123670. 10: Steele JW, Ju S, Lachenmayer ML, Liken J, Stock A, Kim SH, Delgado LM, Alfaro IE, Bernales S, Verdile G, Bharadwaj P, Gupta V, Barr R, Friss A, Dolios G, Wang R, Ringe D, Protter AA, Martins RN, Ehrlich ME, Yue Z, Petsko GA, Gandy S. Latrepirdine stimulates autophagy and reduces accumulation of α-synuclein in cells and in mouse brain. Mol Psychiatry. 2013 Aug;18(8):882-8. doi: 10.1038/mp.2012.115. Epub 2012 Aug 7. PubMed PMID: 22869031; PubMed Central PMCID: PMC3523214. 11: Steele JW, Gandy S. Latrepirdine (Dimebon®), a potential Alzheimer therapeutic, regulates autophagy and neuropathology in an Alzheimer mouse model. Autophagy. 2013 Apr;9(4):617-8. doi: 10.4161/auto.23487. Epub 2013 Feb 4. PubMed PMID: 23380933; PubMed Central PMCID: PMC3627679. 12: Steele JW, Lachenmayer ML, Ju S, Stock A, Liken J, Kim SH, Delgado LM, Alfaro IE, Bernales S, Verdile G, Bharadwaj P, Gupta V, Barr R, Friss A, Dolios G, Wang R, Ringe D, Fraser P, Westaway D, St George-Hyslop PH, Szabo P, Relkin NR, Buxbaum JD, Glabe CG, Protter AA, Martins RN, Ehrlich ME, Petsko GA, Yue Z, Gandy S. Latrepirdine improves cognition and arrests progression of neuropathology in an Alzheimer's mouse model. Mol Psychiatry. 2013 Aug;18(8):889-97. doi: 10.1038/mp.2012.106. Epub 2012 Jul 31. PubMed PMID: 22850627; PubMed Central PMCID: PMC3625697. 13: Bharadwaj PR, Verdile G, Barr RK, Gupta V, Steele JW, Lachenmayer ML, Yue Z, Ehrlich ME, Petsko G, Ju S, Ringe D, Sankovich SE, Caine JM, Macreadie IG, Gandy S, Martins RN. Latrepirdine (dimebon) enhances autophagy and reduces intracellular GFP-Aβ42 levels in yeast. J Alzheimers Dis. 2012;32(4):949-67. doi: 10.3233/JAD-2012-120178. PubMed PMID: 22903131; PubMed Central PMCID: PMC3529125. 14: Chew ML, Mordenti J, Yeoh T, Ranade G, Qiu R, Fang J, Liang Y, Corrigan B. Minimization of CYP2D6 Polymorphic Differences and Improved Bioavailability via Transdermal Administration: Latrepirdine Example. Pharm Res. 2016 Aug;33(8):1873-80. doi: 10.1007/s11095-016-1922-4. Epub 2016 Apr 12. PubMed PMID: 27072954. 15: Day M, Chandran P, Luo F, Rustay NR, Markosyan S, LeBlond D, Fox GB. Latrepirdine increases cerebral glucose utilization in aged mice as measured by [18F]-fluorodeoxyglucose positron emission tomography. Neuroscience. 2011 Aug 25;189:299-304. doi: 10.1016/j.neuroscience.2011.05.032. Epub 2011 May 19. PubMed PMID: 21619913. 16: Kieburtz K, McDermott MP, Voss TS, Corey-Bloom J, Deuel LM, Dorsey ER, Factor S, Geschwind MD, Hodgeman K, Kayson E, Noonberg S, Pourfar M, Rabinowitz K, Ravina B, Sanchez-Ramos J, Seely L, Walker F, Feigin A; Huntington Disease Study Group DIMOND Investigators. A randomized, placebo-controlled trial of latrepirdine in Huntington disease. Arch Neurol. 2010 Feb;67(2):154-60. doi: 10.1001/archneurol.2009.334. Erratum in: Arch Neurol. 2010 Apr;67(4):492. Dimebon in Subjects With Huntington Disease (DIMOND)Investigators of the Huntington Study Group [corrected to Huntington Disease Study Group DIMOND Investigators]. PubMed PMID: 20142523; PubMed Central PMCID: PMC4134015. 17: Sabbagh MN, Shill HA. Latrepirdine, a potential novel treatment for Alzheimer's disease and Huntington's chorea. Curr Opin Investig Drugs. 2010 Jan;11(1):80-91. Review. PubMed PMID: 20047162; PubMed Central PMCID: PMC3346261. 18: Huang Y, Yang Y, Song H, Liu Y, Wang Q. Synthesis of Structurally Diverse 2,3-Fused Indoles via Microwave-Assisted AgSbF6-Catalysed Intramolecular Difunctionalization of o-Alkynylanilines. Sci Rep. 2015 Aug 27;5:13516. doi: 10.1038/srep13516. PubMed PMID: 26310858; PubMed Central PMCID: PMC4550932. 19: Zhang S, Hedskog L, Petersen CA, Winblad B, Ankarcrona M. Dimebon (latrepirdine) enhances mitochondrial function and protects neuronal cells from death. J Alzheimers Dis. 2010;21(2):389-402. doi: 10.3233/JAD-2010-100174. PubMed PMID: 20555134. 20: Steele JW, Kim SH, Cirrito JR, Verges DK, Restivo JL, Westaway D, Fraser P, Hyslop PS, Sano M, Bezprozvanny I, Ehrlich ME, Holtzman DM, Gandy S. Acute dosing of latrepirdine (Dimebon), a possible Alzheimer therapeutic, elevates extracellular amyloid-beta levels in vitro and in vivo. Mol Neurodegener. 2009 Dec 17;4:51. doi: 10.1186/1750-1326-4-51. PubMed PMID: 20017949; PubMed Central PMCID: PMC2806870.