Identification

Name
Almitrine
Accession Number
DB01430
Type
Small Molecule
Groups
Approved
Description

A respiratory stimulant that enhances respiration by acting as an agonist of peripheral chemoreceptors located on the carotid bodies. The drug increases arterial oxygen tension while decreasing arterial carbon dioxide tension in patients with chronic obstructive pulmonary disease. It may also prove useful in the treatment of nocturnal oxygen desaturation without impairing the quality of sleep. [PubChem]

Structure
Thumb
Synonyms
  • 2,4-Bis(allylamino)-6-(4-(bis(P-fluorophenyl)methyl)-1-piperazinyl)-S-triazine
  • Almitrina
  • Almitrinum
Product Ingredients
IngredientUNIICASInChI Key
Almitrine mesylate6RY6V6XM8T29608-49-9MRDBGMJEPGXQHJ-UHFFFAOYSA-N
International/Other Brands
Duxil (Servier) / Vectarion
Categories
UNII
9A1222NBG4
CAS number
27469-53-0
Weight
Average: 477.5522
Monoisotopic: 477.245250373
Chemical Formula
C26H29F2N7
InChI Key
OBDOVFRMEYHSQB-UHFFFAOYSA-N
InChI
InChI=1S/C26H29F2N7/c1-3-13-29-24-31-25(30-14-4-2)33-26(32-24)35-17-15-34(16-18-35)23(19-5-9-21(27)10-6-19)20-7-11-22(28)12-8-20/h3-12,23H,1-2,13-18H2,(H2,29,30,31,32,33)
IUPAC Name
6-{4-[bis(4-fluorophenyl)methyl]piperazin-1-yl}-N2,N4-bis(prop-2-en-1-yl)-1,3,5-triazine-2,4-diamine
SMILES
FC1=CC=C(C=C1)C(N1CCN(CC1)C1=NC(NCC=C)=NC(NCC=C)=N1)C1=CC=C(F)C=C1

Pharmacology

Indication

For the treatment of chronic obstructive pulmonary disease.

Pharmacodynamics

Almitrine is a respiratory stimulant that enhances respiration by acting as an agonist of peripheral chemoreceptors located on the carotid bodies. The drug increases arterial oxygen tension while decreasing arterial carbon dioxide tension in patients with chronic obstructive pulmonary disease. It may also prove useful in the treatment of nocturnal oxygen desaturation without impairing the quality of sleep.

Mechanism of action

Almitrine enhances respiration by acting as an agonist of peripheral chemoreceptors located on the carotid bodies. The drug increases arterial oxygen tension while decreasing arterial carbon dioxide tension in patients with chronic obstructive pulmonary disease.

TargetActionsOrganism
ASodium/potassium-transporting ATPase subunit alpha-1
binder
Human
Absorption
Not Available
Volume of distribution
Not Available
Protein binding
Not Available
Metabolism
Not Available
Route of elimination
Not Available
Half life
Not Available
Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Humans and other mammals
Pathways
Not Available
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
Not Available
Food Interactions
Not Available

References

General References
Not Available
External Links
Human Metabolome Database
HMDB0015499
KEGG Drug
D02822
PubChem Compound
33887
PubChem Substance
46505517
ChemSpider
31235
ChEBI
53778
ChEMBL
CHEMBL1183717
Therapeutic Targets Database
DAP000468
PharmGKB
PA164750492
Wikipedia
Almitrine
ATC Codes
R07AB07 — Almitrine

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
  • Centocor Ortho Biotech Inc.
Dosage forms
Not Available
Prices
Unit descriptionCostUnit
Doxil 2 mg/ml vial115.78USD ml
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
Not Available
Predicted Properties
PropertyValueSource
Water Solubility0.0144 mg/mLALOGPS
logP4.9ALOGPS
logP6.05ChemAxon
logS-4.5ALOGPS
pKa (Strongest Acidic)14.27ChemAxon
pKa (Strongest Basic)7.49ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area69.21 Å2ChemAxon
Rotatable Bond Count10ChemAxon
Refractivity140.88 m3·mol-1ChemAxon
Polarizability51.12 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9844
Blood Brain Barrier+0.8158
Caco-2 permeable-0.5851
P-glycoprotein substrateSubstrate0.7054
P-glycoprotein inhibitor IInhibitor0.8951
P-glycoprotein inhibitor IIInhibitor0.7886
Renal organic cation transporterInhibitor0.6628
CYP450 2C9 substrateNon-substrate0.8937
CYP450 2D6 substrateNon-substrate0.7478
CYP450 3A4 substrateNon-substrate0.6653
CYP450 1A2 substrateInhibitor0.8218
CYP450 2C9 inhibitorNon-inhibitor0.6926
CYP450 2D6 inhibitorInhibitor0.6928
CYP450 2C19 inhibitorInhibitor0.5949
CYP450 3A4 inhibitorNon-inhibitor0.6962
CYP450 inhibitory promiscuityHigh CYP Inhibitory Promiscuity0.7983
Ames testNon AMES toxic0.7426
CarcinogenicityNon-carcinogens0.8823
BiodegradationNot ready biodegradable1.0
Rat acute toxicity2.6869 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Strong inhibitor0.7124
hERG inhibition (predictor II)Inhibitor0.8337
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)
Not Available
Spectra
SpectrumSpectrum TypeSplash Key
Predicted GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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 diphenylmethanes. These are compounds containing a diphenylmethane moiety, which consists of a methane wherein two hydrogen atoms are replaced by two phenyl groups.
Kingdom
Organic compounds
Super Class
Benzenoids
Class
Benzene and substituted derivatives
Sub Class
Diphenylmethanes
Direct Parent
Diphenylmethanes
Alternative Parents
N-arylpiperazines / Dialkylarylamines / Secondary alkylarylamines / N-alkylpiperazines / N-aliphatic s-triazines / Fluorobenzenes / Aralkylamines / Aryl fluorides / 1,3,5-triazines / Heteroaromatic compounds
show 5 more
Substituents
Diphenylmethane / N-arylpiperazine / Dialkylarylamine / Amino-1,3,5-triazine / Aminotriazine / Halobenzene / Fluorobenzene / Secondary aliphatic/aromatic amine / Aralkylamine / N-aliphatic s-triazine
show 21 more
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
triamino-1,3,5-triazine, piperazines (CHEBI:53778)

Targets

Kind
Protein
Organism
Human
Pharmacological action
Yes
Actions
Binder
General Function
Steroid hormone binding
Specific Function
This is the catalytic component of the active enzyme, which catalyzes the hydrolysis of ATP coupled with the exchange of sodium and potassium ions across the plasma membrane. This action creates th...
Gene Name
ATP1A1
Uniprot ID
P05023
Uniprot Name
Sodium/potassium-transporting ATPase subunit alpha-1
Molecular Weight
112895.01 Da
References
  1. Rigoulet M: Control processes in oxidative phosphorylation: kinetic constraints and stoichiometry. Biochim Biophys Acta. 1990 Jul 25;1018(2-3):185-9. [PubMed:2144185]
  2. Rigoulet M, Fraisse L, Ouhabi R, Guerin B, Fontaine E, Leverve X: Flux-dependent increase in the stoichiometry of charge translocation by mitochondrial ATPase/ATP synthase induced by almitrine. Biochim Biophys Acta. 1990 Jul 17;1018(1):91-7. [PubMed:2165421]
  3. Rigoulet M, Ouhabi R, Leverve X, Putod-Paramelle F, Guerin B: Almitrine, a new kind of energy-transduction inhibitor acting on mitochondrial ATP synthase. Biochim Biophys Acta. 1989 Aug 3;975(3):325-9. [PubMed:2527061]
  4. Benzi G, Gorini A, Ghigini B, Arnaboldi R, Villa RF: Synaptosomal non-mitochondrial ATPase activities and drug treatment. Neurochem Res. 1993 Jun;18(6):719-26. [PubMed:8099718]
  5. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. [PubMed:11752352]

Drug created on July 24, 2007 09:02 / Updated on October 01, 2018 16:30