U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ACHIRAL
Molecular Formula C21H25N3
Molecular Weight 319.4433
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of LATREPIRDINE

SMILES

CN1CCC2=C(C1)C3=C(C=CC(C)=C3)N2CCC4=CN=C(C)C=C4

InChI

InChIKey=JNODQFNWMXFMEV-UHFFFAOYSA-N
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

HIDE SMILES / InChI
Molecular Formula C21H25N3
Molecular Weight 319.4433
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/21031168 | https://www.ncbi.nlm.nih.gov/pubmed/18939977

Dimebon (latrepirdine) is an orally available, small molecule, gamma carboline derivative that was developed and used in Russia as an over-the-counter oral antihistamine for allergy treatment since 1980s. In 1990s it was shown that Dimebon has promising potential in treating neurodegenerative diseases. In 2003, Medivation Inc acquired the rights to Dimebon. Medivation went public in December 2004, with Dimebon as the only drug in its pipeline. The product was being developed by Medivation and Pfizer as a treatment for early-stage Alzheimer's disease and Huntington's disease. However, development was discontinued by Medivation and Pfizer in early 2012. Dimebon inhibits alpha-Adrenergic receptors (alpha1A, alpha1B, alpha1D, and alpha2A), Histamine H1 and H2 receptors and Serotonin 5-HT2c, 5-HT5A, 5-HT6 receptors with high affinity. Dimebon may act by blocking NMDA receptors or voltage-gated Ca2+ channels and by preventing mitochondrial permeability pore transition.

CNS Activity

Originator

Shadurski, K.S. et al.
2
Sources: Shadurski KS, Danusevich IK, Kost AN, Vinogradova EV. 1138164 US Patent No. Chem Abstr. 1985;102:190810.
Curator's Comment: Reference retrieved from https://www.ncbi.nlm.nih.gov/pubmed/21517088

Approval Year

Unknown
139594
Targets

Targets

Primary TargetPharmacologyConditionPotency
Antagonist
2778
Antagonist
2778
Inhibitor
8297
 42.0 µM [IC50]
Inhibitor
8297
 7.9 µM [IC50]
Blocker
537
 57.0 µM [IC50]
Inhibitor
8297
Inhibitor
8297
Inhibitor
8297
Inhibitor
8297
Inhibitor
8297
Inhibitor
8297
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Approved
8429
Dimebon

Approved Use

Dimebon was initially developed and launched in Russia (USSR at the time) in 1983 as an over-the-counter oral antihistamine for allergy treatment.

Launch Date

4.10140803E11
Primary
Phase III
656
Unknown

Approved Use

Unknown
Primary
Phase III
656
Unknown

Approved Use

Unknown
PubMed

PubMed

TitleDatePubMed
Antihistamine agent Dimebon as a novel neuroprotector and a cognition enhancer.
2001 Jun
Effect of dimebon on cognition, activities of daily living, behaviour, and global function in patients with mild-to-moderate Alzheimer's disease: a randomised, double-blind, placebo-controlled study.
2008 Jul 19
Evaluation of Dimebon in cellular model of Huntington's disease.
2008 Oct 21
The rise and fall of Dimebon.
2010 Oct
Latrepirdine improves cognition and arrests progression of neuropathology in an Alzheimer's mouse model.
2013 Aug
Patents

Patents

08338408
2
WO2008036400A3
2
WO2008051599A3
2
WO2008112238A1
2

Sample Use Guides

In Vivo Use Guide
As anti-allergic medicine Dimebon was used in doses 10–20 mg 2–3 times per day. Oral dimebon, 20 mg three times a day was tested in Alzheimer's disease patients.
Route of Administration: Oral
In Vitro Use Guide
50 uM Dimebon stabilized glutamate-induced Ca2+ signals in primary striatal neuronal cultures (MSN) from YAC128 HD transgenic mice (YAC128 MSN) and protected cultured YAC128 MSN from glutamate-induced apoptosis. Lower concentrations of Dimebon (5 uM and 10 uM) did not stabilize glutamate-induced Ca2+ signals and did not exert neuroprotective effects in experiments with YAC128 MSN.
Substance Class Chemical
Created
by admin
on Fri Dec 15 16:04:51 UTC 2023
Edited
by admin
on Fri Dec 15 16:04:51 UTC 2023
Record UNII
OD9237K1Z6
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
LATREPIRDINE
INN   MART.   USAN   WHO-DD  
INN   USAN  
Official Name English
Latrepirdine [WHO-DD]
Common Name English
PF-01913539
Common Name English
LATREPIRDINE [MART.]
Common Name English
DIMEBOLIN [MI]
Common Name English
DIMEBOLIN
MI  
Common Name English
2,8-Dimethyl-5-[2-(6-methylpyridin-3-yl)ethyl]-2,3,4,5-tetrahydro-1H-pyrido[4,3-b]indole
Systematic Name English
latrepirdine [INN]
Common Name English
1H-PYRIDO(4,3-B)INDOLE, 2,3,4,5-TETRAHYDRO-2,8-DIMETHYL-5-(2-(6-METHYL-3-PYRIDINYL)ETHYL)-
Systematic Name English
DIMEBON
Common Name English
LATREPIRDINE [USAN]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C29578
Created by admin on Fri Dec 15 16:04:51 UTC 2023 , Edited by admin on Fri Dec 15 16:04:51 UTC 2023
FDA ORPHAN DRUG 282309
Created by admin on Fri Dec 15 16:04:51 UTC 2023 , Edited by admin on Fri Dec 15 16:04:51 UTC 2023
Code System Code Type Description
ChEMBL
CHEMBL589390
Created by admin on Fri Dec 15 16:04:51 UTC 2023 , Edited by admin on Fri Dec 15 16:04:51 UTC 2023
PRIMARY
MERCK INDEX
m4495
Created by admin on Fri Dec 15 16:04:51 UTC 2023 , Edited by admin on Fri Dec 15 16:04:51 UTC 2023
PRIMARY Merck Index
NCI_THESAURUS
C78757
Created by admin on Fri Dec 15 16:04:51 UTC 2023 , Edited by admin on Fri Dec 15 16:04:51 UTC 2023
PRIMARY
SMS_ID
100000124365
Created by admin on Fri Dec 15 16:04:51 UTC 2023 , Edited by admin on Fri Dec 15 16:04:51 UTC 2023
PRIMARY
EPA CompTox
DTXSID20189705
Created by admin on Fri Dec 15 16:04:51 UTC 2023 , Edited by admin on Fri Dec 15 16:04:51 UTC 2023
PRIMARY
INN
9207
Created by admin on Fri Dec 15 16:04:51 UTC 2023 , Edited by admin on Fri Dec 15 16:04:51 UTC 2023
PRIMARY
EVMPD
SUB32096
Created by admin on Fri Dec 15 16:04:51 UTC 2023 , Edited by admin on Fri Dec 15 16:04:51 UTC 2023
PRIMARY
MESH
C010119
Created by admin on Fri Dec 15 16:04:51 UTC 2023 , Edited by admin on Fri Dec 15 16:04:51 UTC 2023
PRIMARY
CAS
3613-73-8
Created by admin on Fri Dec 15 16:04:51 UTC 2023 , Edited by admin on Fri Dec 15 16:04:51 UTC 2023
PRIMARY
DRUG BANK
DB11725
Created by admin on Fri Dec 15 16:04:51 UTC 2023 , Edited by admin on Fri Dec 15 16:04:51 UTC 2023
PRIMARY
FDA UNII
OD9237K1Z6
Created by admin on Fri Dec 15 16:04:51 UTC 2023 , Edited by admin on Fri Dec 15 16:04:51 UTC 2023
PRIMARY
USAN
WW-164
Created by admin on Fri Dec 15 16:04:51 UTC 2023 , Edited by admin on Fri Dec 15 16:04:51 UTC 2023
PRIMARY
PUBCHEM
197033
Created by admin on Fri Dec 15 16:04:51 UTC 2023 , Edited by admin on Fri Dec 15 16:04:51 UTC 2023
PRIMARY
WIKIPEDIA
Latrepirdine
Created by admin on Fri Dec 15 16:04:51 UTC 2023 , Edited by admin on Fri Dec 15 16:04:51 UTC 2023
PRIMARY
Related Record Type Details
5-HYDROXYTRYPTAMINE RECEPTOR 6
TARGET -> INHIBITOR
Ki
5-HYDROXYTRYPTAMINE RECEPTOR 7
TARGET -> INHIBITOR
Ki
HISTAMINE H1 RECEPTOR
TARGET -> INHIBITOR
IC50
HISTAMINE H2 RECEPTOR
TARGET->WEAK INHIBITOR
IC50
POTASSIUM VOLTAGE-GATED CHANNEL SUBFAMILY H MEMBER 2
OFF-TARGET->INHIBITOR
Related Record Type Details
Structure of LATREPIRDINE
ACTIVE MOIETY
NIH
NCATS
PRIVACY ACT
ACCESSIBILITY
DISCLAIMER
HHS VULNERABILITY DISCLOSURE
For language access assistance, contact the NCATS Public Information Officer
National Center for Advancing Translational Sciences (NCATS),
6701 Democracy Boulevard, Bethesda MD 20892-4874 • 301-594-8966