Synonym
Latrepirdine HCl, Dimebolin HCl, Dimebon HCl,
IUPAC/Chemical Name
2,8-dimethyl-5-(2-(6-methylpyridin-3-yl)ethyl)-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole dihydrochloride
InChi Key
GTWLIQOLGOZTLF-UHFFFAOYSA-N
InChi Code
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
SMILES Code
CC1=CC=C(CCN2C3=C(CN(C)CC3)C4=C2C=CC(C)=C4)C=N1.[H]Cl.[H]Cl
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
>2 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
2934.99.9001
Biological target:
Latrepirdine dihydrochloride is a neuroactive compound with antagonist activity at histaminergic, α-adrenergic, and serotonergic receptors.
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/
|
Solvent |
mg/mL |
mM |
| Solubility |
| DMF |
1.0 |
2.55 |
| DMSO |
7.1 |
18.18 |
| Ethanol |
6.5 |
16.57 |
| PBS (pH 7.2) |
10.0 |
25.49 |
| Water |
100.0 |
254.86 |
Note: There can be variations in solubility for the same chemical from different vendors or different batches from the same vendor. The following factors can affect the solubility of the same chemical: solvent used for crystallization, residual solvent content, polymorphism, salt versus free form, degree of hydration, solvent temperature. Please use the solubility data as a reference only. Warming and sonication will facilitate dissolving. Still have questions? Please contact our Technical Support scientists.
Preparing Stock Solutions
The following data is based on the
product
molecular weight
392.37
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:
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.
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: Vignisse J, Steinbusch HW, Bolkunov A, Nunes J, Santos AI, Grandfils C, Bachurin S, Strekalova T. Dimebon enhances hippocampus-dependent learning in both appetitive and inhibitory memory tasks in mice. Prog Neuropsychopharmacol Biol Psychiatry. 2010 Dec 14. [Epub ahead of print] PubMed PMID: 21163318.
2: Bachurin SO, Ustyugov AA, Peters O, Shelkovnikova TA, Buchman VL, Ninkina NN. Hindering of proteinopathy-induced neurodegeneration as a new mechanism of action for neuroprotectors and cognition enhancing compounds. Dokl Biochem Biophys. 2009 Sep-Oct;428:235-8. PubMed PMID: 20848907.
3: Tabira T. [Development of new drugs for Alzheimer's disease]. Brain Nerve. 2010 Jul;62(7):787-96. Review. Japanese. PubMed PMID: 20675883.
4: Shoji M. [Drug therapy for Alzheimer's disease]. Brain Nerve. 2010 Jul;62(7):777-85. Review. Japanese. PubMed PMID: 20675882.
5: Learning from failure. Nat Rev Drug Discov. 2010 Jul;9(7):499. PubMed PMID: 20614555.
6: 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. PubMed PMID: 20555134.
7: Sachdeva D, Burns A. Dimebolin in Dementia. CNS Neurosci Ther. 2010 Jun 11. [Epub ahead of print] PubMed PMID: 20553307.
8: Mechanism matters. Nat Med. 2010 Apr;16(4):347. PubMed PMID: 20376007.
9: Gao M, Wang M, Hutchins GD, Zheng QH. [(11)C]Dimebon, radiosynthesis and lipophilicity of a new potential PET agent for imaging of Alzheimer's disease and Huntington's disease. Bioorg Med Chem Lett. 2010 Apr 15;20(8):2529-32. Epub 2010 Mar 3. PubMed PMID: 20299213.
10: Miller G. Pharmacology. The puzzling rise and fall of a dark-horse Alzheimer's drug. Science. 2010 Mar 12;327(5971):1309. PubMed PMID: 20223954.
