Cat. No.: HY-14862

Latrepirdine

(Synonyms: Dimebolin; Dimebone)

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Latrepirdine is a neuroactive compound with antagonist activity at histaminergic, α-adrenergic, and serotonergic receptors. Latrepirdine stimulates amyloid precursor protein (APP) catabolism and amyloid-β (Aβ) secretion.

For research use only. We do not sell to patients.

Purity: 99.51%
CAS No.: 3613-73-8
Formula: C₂₁H₂₅N₃
Molecular Weight:319.44

Storage:

Powder -20°C, 3 years , 4°C, 2 years ; In solvent -80°C, 6 months , -20°C, 1 month

Latrepirdine Chemical Structure

CAS No.: 3613-73-8

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Top Publications Citing

Use of MCE Products

Fluorescent Dye

Strong Fluorescence Signal / Multi-Disciplinary Applications / High Fluorescence Specificity

Biological Activity
- Description
- IC₅₀ & Target
- Cellular Effect
- In Vitro
- In Vivo
- Clinical Trial
Chemical Information
Solvent & Solubility
- In Vitro
- In Vivo
Protocol
Purity & Documentation
References
Help & FAQs
Classifications
Bioz

Biological Activity

Description

IC₅₀ & Target

Amyloid-β (Aβ), Histaminergic receptor, α-adrenergic receptor, Serotonergic receptor^[1]

All Histamine Receptor Isoforms :

All Adrenergic Receptor Isoforms :

All 5-HT Receptor Isoforms :

Cellular Effect

Cell Line	Type	Value	Description	References
HEK293	IC₅₀	0.89 μM Compound: 3{1}, I, Dimebone, dimebolin	Antagonist activity at human recombinant 5-HT6 receptor expressed in HEK293 cells assessed as inhibition of serotonin-induced intracellular cAMP accumulation by LANCE technique Antagonist activity at human recombinant 5-HT6 receptor expressed in HEK293 cells assessed as inhibition of serotonin-induced intracellular cAMP accumulation by LANCE technique	[PMID: 19443217]
HEK293	IC₅₀	0.89 μM Compound: Dimebolin	Antagonist activity at human recombinant 5HT6 receptor expressed in HEK293 cells assessed as inhibition of serotonin-induced cAMP production by LANCE assay Antagonist activity at human recombinant 5HT6 receptor expressed in HEK293 cells assessed as inhibition of serotonin-induced cAMP production by LANCE assay	[PMID: 19939513]
HEK293	IC₅₀	1.16 μM Compound: Dimebolin	Antagonist activity at human recombinant 5HT6 receptor expressed in HEK293 cells assessed as inhibition of serotonin-induced increase in intracellular cAMP level by cAMP-LANCE method Antagonist activity at human recombinant 5HT6 receptor expressed in HEK293 cells assessed as inhibition of serotonin-induced increase in intracellular cAMP level by cAMP-LANCE method	[PMID: 19945877]
SK-N-SH	IC₅₀	0.158 μM Compound: Dimebolin	Antagonist activity at histamine H1 receptor in human SK-N-SH cells assessed as histamine-induced maximum intracellular calcium spike at phase 1 treated 10 to 15 seconds before histamine challenge Antagonist activity at histamine H1 receptor in human SK-N-SH cells assessed as histamine-induced maximum intracellular calcium spike at phase 1 treated 10 to 15 seconds before histamine challenge	[PMID: 19945877]
SK-N-SH	IC₅₀	0.16 μM Compound: 3{1}, I, Dimebone, dimebolin	Antagonist activity at human histamine H1 receptor in SK-N-SH cells assessed as inhibition of histamine-induced calcium level increase during phase-1 compound incubated before histamine addition by Fura-2 based fluorometric assay Antagonist activity at human histamine H1 receptor in SK-N-SH cells assessed as inhibition of histamine-induced calcium level increase during phase-1 compound incubated before histamine addition by Fura-2 based fluorometric assay	[PMID: 19443217]
SK-N-SH	IC₅₀	1.58 μM Compound: 3{1}, I, Dimebone, dimebolin	Antagonist activity at human histamine H1 receptor in SK-N-SH cells assessed as inhibition of histamine-induced calcium flow during phase-II compound dosed after histamine addition by Fura-2 based fluorometric assay Antagonist activity at human histamine H1 receptor in SK-N-SH cells assessed as inhibition of histamine-induced calcium flow during phase-II compound dosed after histamine addition by Fura-2 based fluorometric assay	[PMID: 19443217]
SK-N-SH	IC₅₀	1.58 μM Compound: Dimebolin	Antagonist activity at histamine H1 receptor in human SK-N-SH cells assessed as reduction of histamine-induced intracellular calcium spike at phase 2 treated 20 to 30 seconds after histamine challenge Antagonist activity at histamine H1 receptor in human SK-N-SH cells assessed as reduction of histamine-induced intracellular calcium spike at phase 2 treated 20 to 30 seconds after histamine challenge	[PMID: 19945877]

In Vitro

Latrepirdine has been reported to possess several properties that are potentially relevant to the treatment of neurodegenerative diseases: (1) protection of cultured cells from the cytotoxicity of amyloid-β (Aβ) peptide; (2) stabilization of mitochondrial function and calcium homeostasis; (3) modulation of Aβ release from cultured cells, isolated intact nerve terminals, and from hippocampal neurons in living mouse brain; and (4) promotion of neurogenesis in the murine hippocampus. Treatment of cultured mammalian cells with Latrepirdine leads to enhanced mTOR- and Atg5-dependent autophagy. Latrepirdine modulates Atg5-dependent autophagic activity in a dose-dependent manner and via the mTOR-signaling pathway. HeLa cells stably expressing LC3 fused are treated with EGFP (eGFP-LC3) for 3 or 6 hours in the absence or presence of 50 μM Latrepirdine. Treatment with Latrepirdine for 3 or 6 hours markedly enhances the number of eGFP-LC3 punctae, indicating that Latrepirdine induces formation of autophagosomes. Next, mouse N2a neuroblastoma cells are treated in the absence (vehicle) or presence of 5 nM, 500 nM or 50 μM Latrepirdine for 3 or 6 hours in order to determine the effects of acute drug treatment on the regulation of autophagy. A significant and dose-dependent increase is observed in LC3-II levels in N2a cells following 3- or 6-hour treatment with either 500 nM or 50 μM Latrepirdine. A significant decrease of p-mTOR and p-S6K from N2a cells treated with 50 μM Latrepirdine for 3 hours is observed, whereas the total mTOR and p70S6K levels remain relatively constant^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

In Vivo

Latrepirdine treatment of TgCRND8 transgenic mice is associated with improved learning behavior and with a reduction in accumulation of Aβ42 and α-synuclein. Male, 90-day-old TgCRND8 mice or their wild-type littermates (nTg) receive 31 consecutive once daily i.p. injections of either 3.5 mg/kg Latrepirdine or 0.9% saline (vehicle). At the culmination of treatment, mice are tested for cued and contextual fear conditioning using a paradigm that has been widely accepted for evaluating learning and memory deficits in APP transgenic mice. A significant increase in cued memory only among Latrepirdine-versus vehicle-treated TgCRND8 mice (p=0.01) is observed. A weak, non-significant trend toward an improvement in contextual memory among Latrepirdine-versus vehicle-treated mice (p=0.099) is also observed^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Clinical Trial

NCT Number	Sponsor	Condition	Start Date	Phase A549
NCT01329991	Plexxikon\|		2011-05	PHASE1

Chemical Information

CAS No. 3613-73-8
Appearance Solid
Molecular Weight 319.44
Formula C₂₁H₂₅N₃
Color White to off-white
SMILES

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

Dimebolin; Dimebone
Shipping

Room temperature in continental US; may vary elsewhere.

Storage

Powder	-20°C	3 years
	4°C	2 years
In solvent	-80°C	6 months
	-20°C	1 month

Solvent & Solubility

In Vitro:

Ethanol : 25 mg/mL (78.26 mM; Need ultrasonic)

View the Complete Stock Solution Preparation Table

Preparing Stock Solutions

View the Complete Stock Solution Preparation Table

Concentration Solvent Mass

1 mg

5 mg

10 mg

Concentration

Solvent

Mass

1 mM

3.1305 mL

15.6524 mL

31.3048 mL

5 mM

0.6261 mL

3.1305 mL

6.2610 mL

10 mM

0.3130 mL

1.5652 mL

3.1305 mL

Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.

Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Molarity Calculator

Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

Mass Mass

Concentration Concentration

Volume Volume

Molecular Weight Molecular Weight

Dilution Calculator

Concentration _(start) × Volume _(start) = Concentration _(final) × Volume _(final)

Concentration _(start) Concentration _(start)

Volume _(start) Volume _(start)

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In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

Stock Solution Working Solution

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

Protocol 1

Add each solvent one by one: 10% EtOH 90% (20% SBE-β-CD in Saline)

Solubility: ≥ 2.5 mg/mL (7.83 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).

Taking 1 mL working solution as an example, add 100 μL EtOH stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.

Protocol 2

Add each solvent one by one: 10% EtOH 90% Corn Oil

Solubility: ≥ 2.5 mg/mL (7.83 mM); Clear solution

This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

Taking 1 mL working solution as an example, add 100 μL EtOH stock solution (25.0 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator

Please enter the basic information of animal experiments:

Dosage Dosage
mg/kg
Animal Weight (Per Animal) Animal Weight (Per Animal)
g
Dosing Volume (Per Animal) Dosing Volume (Per Animal)
μL
Number of Animals Number of Animals

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.

Working solution concentration: 0.22 mg/mL

Protocol

Cell Assay^[1]

N2a cells, stable human cervical carcinoma (HeLa) cells expressing EGFP-LC3, and mouse embryonic fibroblasts (MEFs) derived from wildtype mice or ATG5^-/- mice are maintained in “growth medium” (high glucose Dulbecco's modified Eagle's medium supplemented with 10% FBS and 100 units/mL Penicillin/Streptomycin) at 37°C, 5% CO₂. N2a cells stably transfected with APPK670N, M671L are maintained in growth medium supplemented with 0.2 mg/mL G418. Cells are washed 1× with ice cold PBS (pH 7.4) then incubated with either Latrepirdine (5 nM, 500 nM or 50 μM) or vehicle (growth medium). Following 3-, 6-, or 24-hour of treatment, cells are washed 1x with ice cold PBS, and collected in lysis buffer (50 mM Tris-HCl, 150 mM NaCl, 1 mM Pepstatin, 1 mM PMSF, 1% Triton X-100, EDTA-free mini-complete protease inhibitor cocktail tablet) then centrifuged (14,000 RPM) for 15 minutes at 4°C. For time-course experiments, cells are washed 2× with ice-cold PBS (pH 7.4) and incubated for the indicated time in serum-free DMEM containing 50 μg/mL CHX or 50 μg/mL Cycloheximide (CHX)+50 μg/mL Chloroquine (CQ). Baseline (T₀) samples are collected immediately prior to treatment^[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Administration^[1]

Mice^[1]
Male 53-55-day-old TgCRND8 mice (N=25) are randomly distributed into either of the two treatment groups: Latrepirdine (n=13 TgCRND8) or vehicle (n=12 TgCRND8). Animals receive 21 consecutive once daily intraperitoneal injections of either 3.5 mg/kg Latrepirdine or 0.9% saline (vehicle). 90-day-old male TgCRND8 mice (N=28) or their wild-type littermates (N=56) are randomly distributed into either of two treatment groups: Latrepirdine (n=13 TgCRND8; n=21 nTg) or vehicle (n=15 TgCRND8; n=25 nTg). Following treatment, animals are sacrificed and transcardially perfused with ice-cold PBS (pH 7.4). Male 90-day-old (n=5 per genotype) or 120-day-old (n=6 per genotype) TgCRND8 mice or their non-transgenic littermates are sacrificed and transcardially perfused with ice-cold PBS (pH 7.4). One hemisphere from each mouse is post-fixed in 4% paraformaldeyhde in PBS (pH 7.4) for histological analysis and the other hemisphere is dissected and snap-frozen for biochemical analysis.

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Purity & Documentation

Select Batch:

Purity: 99.98%

Assay: 99.98%

ee.: 99.98%

Data Sheet (280 KB)
SDS (393 KB)
- English - EN (393 KB)
- Français - FR (393 KB)
- Deutsch - DE (393 KB)
- Norwegian - NO (393 KB)
- Español - ES (393 KB)
- Swedish - SV (393 KB)
- Italian - IT (393 KB)
- Korean - KR (393 KB)
- Portuguese - PT (393 KB)
COA (2659 KB)
Elemental Analysis Report (2659 KB)
HNMR (2659 KB)
CNMR (2659 KB)
RP-HPLC (2659 KB)
NP-HPLC (2659 KB)
MS (2659 KB)
LCMS (2659 KB)
IR (2659 KB)
GC (2659 KB)
OR (2659 KB)
SDS-PAGE (2659 KB)
SEC-HPLC (2659 KB)
Other Report (2659 KB)
Handling Instructions (2659 KB)

References

[1]. Steele JW, et al. Latrepirdine improves cognition and arrests progression of neuropathology in an Alzheimer's mouse model. Mol Psychiatry. 2013 Aug;18(8):889-97. [Content Brief]

Help & FAQs

How should lyophilized recombinant proteins be reconstituted and stored?

1. Before opening the cap, centrifuge the vial at 13000 rpm for 20-30 seconds. This step will ensure that any lyophilized powder that may have adhered to the cap or walls is collected at the bottom of the vial, minimizing the risk of product loss.

Complete Stock Solution Preparation Table

Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Optional Solvent	Concentration Solvent Mass	1 mg	5 mg	10 mg	25 mg
Ethanol	1 mM	3.1305 mL	15.6524 mL	31.3048 mL	78.2620 mL
	5 mM	0.6261 mL	3.1305 mL	6.2610 mL	15.6524 mL
	10 mM	0.3130 mL	1.5652 mL	3.1305 mL	7.8262 mL
	15 mM	0.2087 mL	1.0435 mL	2.0870 mL	5.2175 mL
	20 mM	0.1565 mL	0.7826 mL	1.5652 mL	3.9131 mL
	25 mM	0.1252 mL	0.6261 mL	1.2522 mL	3.1305 mL
	30 mM	0.1043 mL	0.5217 mL	1.0435 mL	2.6087 mL
	40 mM	0.0783 mL	0.3913 mL	0.7826 mL	1.9565 mL
	50 mM	0.0626 mL	0.3130 mL	0.6261 mL	1.5652 mL
	60 mM	0.0522 mL	0.2609 mL	0.5217 mL	1.3044 mL

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Latrepirdine

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All Histamine Receptor Isoforms

All Adrenergic Receptor Isoforms

All 5-HT Receptor Isoforms

Biological Activity

Chemical Information

Solvent & Solubility

Protocol

Purity & Documentation

References

Help & FAQs

Complete Stock Solution Preparation Table

Latrepirdine Related Classifications

Cat. No.: HY-14862