Identification

Name
Iproniazid
Accession Number
DB04818
Type
Small Molecule
Groups
Withdrawn
Description

Withdrawn from the Canadian market in July 1964 due to interactions with food products containing tyrosine.

Structure
Thumb
Synonyms
Not Available
International/Other Brands
Euphozid / Iprazid / Ipronid (A.F.I.) / Ipronin / Marsilid (Genopharm) / Rivivol (Zambeletti)
Categories
UNII
D892HFI3XA
CAS number
54-92-2
Weight
Average: 179.219
Monoisotopic: 179.105862053
Chemical Formula
C9H13N3O
InChI Key
NYMGNSNKLVNMIA-UHFFFAOYSA-N
InChI
InChI=1S/C9H13N3O/c1-7(2)11-12-9(13)8-3-5-10-6-4-8/h3-7,11H,1-2H3,(H,12,13)
IUPAC Name
N'-(propan-2-yl)pyridine-4-carbohydrazide
SMILES
CC(C)NNC(=O)C1=CC=NC=C1

Pharmacology

Indication

For the treatment of depression (originally intended to treat tuberculosis).

Pharmacodynamics

Iproniazid is a monoamine oxidase inhibitor (MAOI) that was developed as the first anti-depressant.

Mechanism of action
Not Available
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
DrugInteraction
(R)-warfarinThe risk or severity of bleeding and hemorrhage can be increased when Iproniazid is combined with (R)-warfarin.
(S)-WarfarinThe metabolism of (S)-Warfarin can be decreased when combined with Iproniazid.
1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic AcidIproniazid may increase the hypotensive activities of 1-(3-Mercapto-2-Methyl-Propionyl)-Pyrrolidine-2-Carboxylic Acid.
2,4-thiazolidinedioneIproniazid may increase the hypoglycemic activities of 2,4-thiazolidinedione.
2,5-Dimethoxy-4-ethylamphetamineIproniazid may increase the hypertensive activities of 2,5-Dimethoxy-4-ethylamphetamine.
2,5-Dimethoxy-4-ethylthioamphetamineIproniazid may increase the hypertensive activities of 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineIproniazid may increase the hypertensive activities of 3,4-Methylenedioxyamphetamine.
3,5-DinitrocatecholThe risk or severity of adverse effects can be increased when 3,5-Dinitrocatechol is combined with Iproniazid.
4-Bromo-2,5-dimethoxyamphetamineIproniazid may increase the hypertensive activities of 4-Bromo-2,5-dimethoxyamphetamine.
4-hydroxycoumarinThe risk or severity of bleeding and hemorrhage can be increased when Iproniazid is combined with 4-hydroxycoumarin.
Food Interactions
Not Available

References

Synthesis Reference

U.S. Patent 2,685,585.

General References
Not Available
External Links
KEGG Drug
D02579
KEGG Compound
C11777
PubChem Compound
3748
PubChem Substance
46505059
ChemSpider
3617
BindingDB
29136
ChEBI
5958
ChEMBL
CHEMBL92401
Wikipedia
Iproniazid

Clinical Trials

Clinical Trials
Not Available

Pharmacoeconomics

Manufacturers
Not Available
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)161-161.5U.S. Patent 2,685,585.
logP0.37HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility0.674 mg/mLALOGPS
logP0.02ALOGPS
logP0.31ChemAxon
logS-2.4ALOGPS
pKa (Strongest Acidic)13.66ChemAxon
pKa (Strongest Basic)3.82ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area54.02 Å2ChemAxon
Rotatable Bond Count3ChemAxon
Refractivity60.96 m3·mol-1ChemAxon
Polarizability19.19 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9929
Blood Brain Barrier+0.9799
Caco-2 permeable+0.6657
P-glycoprotein substrateNon-substrate0.7484
P-glycoprotein inhibitor INon-inhibitor0.9191
P-glycoprotein inhibitor IINon-inhibitor0.9932
Renal organic cation transporterNon-inhibitor0.9166
CYP450 2C9 substrateNon-substrate0.8608
CYP450 2D6 substrateNon-substrate0.873
CYP450 3A4 substrateNon-substrate0.614
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.9316
CYP450 2D6 inhibitorNon-inhibitor0.9522
CYP450 2C19 inhibitorNon-inhibitor0.9293
CYP450 3A4 inhibitorNon-inhibitor0.7165
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9221
Ames testNon AMES toxic0.5653
CarcinogenicityNon-carcinogens0.7081
BiodegradationNot ready biodegradable0.9893
Rat acute toxicity2.6600 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9869
hERG inhibition (predictor II)Non-inhibitor0.943
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 pyridinecarboxylic acids and derivatives. These are compounds containing a pyridine ring bearing a carboxylic acid group or a derivative thereof.
Kingdom
Organic compounds
Super Class
Organoheterocyclic compounds
Class
Pyridines and derivatives
Sub Class
Pyridinecarboxylic acids and derivatives
Direct Parent
Pyridinecarboxylic acids and derivatives
Alternative Parents
Heteroaromatic compounds / Carboxylic acid hydrazides / Azacyclic compounds / Organopnictogen compounds / Organooxygen compounds / Organonitrogen compounds / Organic oxides / Hydrocarbon derivatives
Substituents
Pyridine carboxylic acid or derivatives / Heteroaromatic compound / Carboxylic acid hydrazide / Azacycle / Carboxylic acid derivative / Organic nitrogen compound / Organic oxygen compound / Organopnictogen compound / Organic oxide / Hydrocarbon derivative
Molecular Framework
Aromatic heteromonocyclic compounds
External Descriptors
carbohydrazide, pyridines (CHEBI:5958) / a small molecule (IPRONIAZID)

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
Unknown
General Function
Primary amine oxidase activity
Specific Function
Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral...
Gene Name
MAOB
Uniprot ID
P27338
Uniprot Name
Amine oxidase [flavin-containing] B
Molecular Weight
58762.475 Da
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Responsible for the metabolism of many drugs and environmental chemicals that it oxidizes. It is involved in the metabolism of drugs such as antiarrhythmics, adrenoceptor antagonists, and tricyclic...
Gene Name
CYP2D6
Uniprot ID
P10635
Uniprot Name
Cytochrome P450 2D6
Molecular Weight
55768.94 Da
References
  1. Polasek TM, Elliot DJ, Somogyi AA, Gillam EM, Lewis BC, Miners JO: An evaluation of potential mechanism-based inactivation of human drug metabolizing cytochromes P450 by monoamine oxidase inhibitors, including isoniazid. Br J Clin Pharmacol. 2006 May;61(5):570-84. doi: 10.1111/j.1365-2125.2006.02627.x. [PubMed:16669850]
Kind
Protein
Organism
Human
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Steroid hydroxylase activity
Specific Function
Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally un...
Gene Name
CYP2C9
Uniprot ID
P11712
Uniprot Name
Cytochrome P450 2C9
Molecular Weight
55627.365 Da
References
  1. Polasek TM, Elliot DJ, Somogyi AA, Gillam EM, Lewis BC, Miners JO: An evaluation of potential mechanism-based inactivation of human drug metabolizing cytochromes P450 by monoamine oxidase inhibitors, including isoniazid. Br J Clin Pharmacol. 2006 May;61(5):570-84. doi: 10.1111/j.1365-2125.2006.02627.x. [PubMed:16669850]

Drug created on September 11, 2007 14:12 / Updated on November 02, 2018 06:05