Identification

Name
Dimetacrine
Accession Number
DB08996
Type
Small Molecule
Groups
Approved, Withdrawn
Description

Dimetacrine (Istonil, Istonyl, Linostil, Miroistonil), also known as dimethacrine and acripramine, is a tricyclic antidepressant (TCA) with imipramine-like effects used in Europe and formerly in Japan for the treatment of depression.

Structure
Thumb
Synonyms
  • 3-(9,9-dimethylacridin-10-yl)-N,N-dimethyl-propan-1-amine
  • Dimetacrine
  • Istonil
  • Istonyl
  • Linostil
  • Miroistonil
Product Ingredients
IngredientUNIICASInChI Key
Dimetacrine bitartrateDVH164X0IF3759-07-7IIYKUJVECNNTEY-LREBCSMRSA-N
Dimetacrine tartrateNot AvailableNot AvailableNot applicable
Categories
UNII
O341NY501N
CAS number
4757-55-5
Weight
Average: 294.4338
Monoisotopic: 294.209598842
Chemical Formula
C20H26N2
InChI Key
RYQOGSFEJBUZBX-UHFFFAOYSA-N
InChI
InChI=1S/C20H26N2/c1-20(2)16-10-5-7-12-18(16)22(15-9-14-21(3)4)19-13-8-6-11-17(19)20/h5-8,10-13H,9,14-15H2,1-4H3
IUPAC Name
[3-(9,9-dimethyl-9,10-dihydroacridin-10-yl)propyl]dimethylamine
SMILES
CN(C)CCCN1C2=CC=CC=C2C(C)(C)C2=CC=CC=C12

Pharmacology

Indication
Not Available
Structured Indications
Not Available
Pharmacodynamics

Little is known about the pharmacology of dimetacrine.

Mechanism of action
TargetActionsOrganism
AAcetylcholinesterase
antagonist
Human
Absorption
Not Available
Volume of distribution

The highest concentrations of dimetacrine were found at 1 hour after administration but at 3 hours in brain, heart, lung, liver, spleen, kidney, skeletal muscle and adipose tissue of testes. (Carried out in mice, PMID 5312397).

Protein binding
Not Available
Metabolism
Not Available
Route of elimination

Approximately 70% of the doses were excreted in urine and feces within 2 days after treatment. (PMID 5312397)

Half life

Approximately 10 hours. (PMID 5312397)

Clearance
Not Available
Toxicity

Dimetacrine may induce severe cardiac toxicity in overdose. This property is unique among the tricyclic antidepressants.

Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
VemurafenibThe risk or severity of QTc prolongation can be increased when Vemurafenib is combined with Dimetacrine.Approved
Food Interactions
Not Available

References

Synthesis Reference

GB933875

General References
  1. Ishitani R, Saito E, Kitagawa H: The pharmacological studies on dimetacrine. I. Studies on the absorption, distribution and excretion of H3-labeled dimetacrine in the rat. Jpn J Pharmacol. 1970 Sep;20(3):432-8. [PubMed:5312397]
External Links
KEGG Drug
D02565
KEGG Compound
C12959
PubChem Compound
94280
PubChem Substance
310264957
ChemSpider
85085
ChEBI
135233
ChEMBL
CHEMBL1328913
Wikipedia
Dimetacrine
ATC Codes
N06AA18 — Dimetacrine

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Patent NumberPediatric ExtensionApprovedExpires (estimated)
US3284454No1966-11-081986-11-08Us

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)155-156U.S. Patent 3,284,454.
Predicted Properties
PropertyValueSource
Water Solubility0.0343 mg/mLALOGPS
logP4.96ALOGPS
logP4.42ChemAxon
logS-3.9ALOGPS
pKa (Strongest Basic)9.2ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count2ChemAxon
Hydrogen Donor Count0ChemAxon
Polar Surface Area6.48 Å2ChemAxon
Rotatable Bond Count4ChemAxon
Refractivity105.52 m3·mol-1ChemAxon
Polarizability35.87 Å3ChemAxon
Number of Rings3ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
Not Available

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This compound belongs to the class of organic compounds known as acridines. These are organic compounds containing the acridine moiety, a linear tricyclic heterocycle which consists of two benzene rings joined by a pyridine ring.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Quinolines and derivatives
Sub Class
Benzoquinolines
Direct Parent
Acridines
Alternative Parents
Alkyldiarylamines / Benzenoids / Trialkylamines / Azacyclic compounds / Organopnictogen compounds / Hydrocarbon derivatives
Substituents
Acridine / Alkyldiarylamine / Tertiary aliphatic/aromatic amine / Benzenoid / Tertiary aliphatic amine / Tertiary amine / Azacycle / Organic nitrogen compound / Organopnictogen compound / Hydrocarbon derivative
Molecular Framework
Aromatic heteropolycyclic compounds
External Descriptors
Not Available

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Antagonist
General Function
Serine hydrolase activity
Specific Function
Terminates signal transduction at the neuromuscular junction by rapid hydrolysis of the acetylcholine released into the synaptic cleft. Role in neuronal apoptosis.
Gene Name
ACHE
Uniprot ID
P22303
Uniprot Name
Acetylcholinesterase
Molecular Weight
67795.525 Da
References
  1. Ishitani R, Sato T, Suga T, Kitagawa H: Studies on the ultrastructural distribution of H 3 -dimetacrine in rat cerebral cortex. Jpn J Pharmacol. 1972 Jun;22(3):313-23. [PubMed:4539395]

Drug created on June 16, 2014 13:04 / Updated on December 01, 2017 17:19