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Identification
NameProcarbazine
Accession NumberDB01168  (APRD00695)
TypeSmall Molecule
GroupsApproved
Description

An antineoplastic agent used primarily in combination with mechlorethamine, vincristine, and prednisone (the MOPP protocol) in the treatment of Hodgkin’s disease. [PubChem]

Structure
Thumb
Synonyms
1-Methyl-2-(P-(isopropylcarbamoyl)benzyl)hydrazine
2-(P-Isopropylcarbamoylbenzyl)-1-methylhydrazine
4-((2-Methylhydrazino)methyl)-N-isopropylbenzamide
N-(1-Methylethyl)-4-((2-methylhydrazino)methyl)benzamide
N-4-Isopropylcarbamoylbenzyl-n'-methylhydrazine
N-Isopropyl-4-[(2-methylhydrazino)methyl]benzamide
N-Isopropyl-alpha-(2-methylhydrazino)-P-toluamide
N-Isopropyl-P-(2-methylhydrazinomethyl)-benzamide
P-(2-Methylhydrazinomethyl)-N-isopropylbenzamide
Procarbazin
Procarbazina
Procarbazinum
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Matulanecapsule50 mg/1oralSigma Tau Pharmaceuticals, Inc.1985-12-27Not applicableUs
Matulanecapsule50 mgoralSigma Tau Pharmaceuticals Inc1970-12-31Not applicableCanada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
IndicarbNot Available
NatulanNot Available
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Procarbazine hydrochloride
Thumb
  • InChI Key: OCSSHHHAHMCFDV-UHFFFAOYSA-N
  • Monoisotopic Mass: 293.106167723
  • Average Mass: 294.221
DBSALT000731
Categories
UNII35S93Y190K
CAS number671-16-9
WeightAverage: 221.2988
Monoisotopic: 221.152812245
Chemical FormulaC12H19N3O
InChI KeyInChIKey=CPTBDICYNRMXFX-UHFFFAOYSA-N
InChI
InChI=1S/C12H19N3O/c1-9(2)15-12(16)11-6-4-10(5-7-11)8-14-13-3/h4-7,9,13-14H,8H2,1-3H3,(H,15,16)
IUPAC Name
4-[(2-methylhydrazin-1-yl)methyl]-N-(propan-2-yl)benzamide
SMILES
CNNCC1=CC=C(C=C1)C(=O)NC(C)C
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as benzamides. These are organic compounds containing a carboxamido substituent attached to a benzene ring.
KingdomOrganic compounds
Super ClassBenzenoids
ClassBenzene and substituted derivatives
Sub ClassBenzamides
Direct ParentBenzamides
Alternative Parents
Substituents
  • Benzoic acid or derivatives
  • Benzamide
  • Phenylmethylamine
  • Benzylamine
  • Benzoyl
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Hydrazine derivative
  • Carbonyl group
  • Aromatic homomonocyclic compound
Molecular FrameworkAromatic homomonocyclic compounds
External Descriptors
Pharmacology
IndicationFor use with other anticancer drugs for the treatment of stage III and stage IV Hodgkin's disease.
PharmacodynamicsProcarbazine is an antineoplastic in the class of alkylating agents and is used to treat various forms of cancer. Alkylating agents are so named because of their ability to add alkyl groups to many electronegative groups under conditions present in cells. They stop tumor growth by cross-linking guanine bases in DNA double-helix strands - directly attacking DNA. This makes the strands unable to uncoil and separate. As this is necessary in DNA replication, the cells can no longer divide. In addition, these drugs add methyl or other alkyl groups onto molecules where they do not belong which in turn inhibits their correct utilization by base pairing and causes a miscoding of DNA. Procarbazine is cell-phase specific for the S phase of cell division.
Mechanism of actionThe precise mode of cytotoxic action of procarbazine has not been clearly defined. There is evidence that the drug may act by inhibition of protein, RNA and DNA synthesis. Studies have suggested that procarbazine may inhibit transmethylation of methyl groups of methionine into t-RNA. The absence of functional t-RNA could cause the cessation of protein synthesis and consequently DNA and RNA synthesis. In addition, procarbazine may directly damage DNA. Hydrogen peroxide, formed during the auto-oxidation of the drug, may attack protein sulfhydryl groups contained in residual protein which is tightly bound to DNA.
Related Articles
AbsorptionProcarbazine is rapidly and completely absorbed.
Volume of distributionNot Available
Protein bindingNot Available
Metabolism

Procarbazine is metabolized primarily in the liver and kidneys. The drug appears to be auto-oxidized to the azo derivative with the release of hydrogen peroxide. The azo derivative isomerizes to the hydrazone, and following hydrolysis splits into a benzylaldehyde derivative and methylhydrazine. The methylhydrazine is further degraded to CO2 and CH4 and possibly hydrazine, whereas the aldehyde is oxidized to N-isopropylterephthalamic acid, which is excreted in the urine.

SubstrateEnzymesProduct
Procarbazine
Not Available
HydrazineDetails
Procarbazine
Not Available
N-isopropylterephthalamic acidDetails
Route of eliminationNot Available
Half life10 minutes
ClearanceNot Available
ToxicityLD50=785 mg/kg (orally in rats)
Affected organisms
  • Humans and other mammals
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9954
Blood Brain Barrier+0.9855
Caco-2 permeable+0.6013
P-glycoprotein substrateNon-substrate0.5748
P-glycoprotein inhibitor INon-inhibitor0.8839
P-glycoprotein inhibitor IINon-inhibitor0.9771
Renal organic cation transporterNon-inhibitor0.7974
CYP450 2C9 substrateNon-substrate0.8293
CYP450 2D6 substrateNon-substrate0.702
CYP450 3A4 substrateNon-substrate0.5484
CYP450 1A2 substrateInhibitor0.9107
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorInhibitor0.8994
CYP450 3A4 inhibitorNon-inhibitor0.8308
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.9414
Ames testNon AMES toxic0.9132
CarcinogenicityCarcinogens 0.6428
BiodegradationNot ready biodegradable0.9741
Rat acute toxicity2.4348 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9785
hERG inhibition (predictor II)Non-inhibitor0.9287
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
ManufacturersNot Available
Packagers
Dosage forms
FormRouteStrength
Capsuleoral50 mg/1
Capsuleoral50 mg
Prices
Unit descriptionCostUnit
Matulane 50 mg capsule55.68USD capsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point223 °CNot Available
water solubility1420 mg/LNot Available
logP0.06HANSCH,C ET AL. (1995)
Predicted Properties
PropertyValueSource
Water Solubility0.228 mg/mLALOGPS
logP0.53ALOGPS
logP0.99ChemAxon
logS-3ALOGPS
pKa (Strongest Acidic)15.03ChemAxon
pKa (Strongest Basic)5.6ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count3ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area53.16 Å2ChemAxon
Rotatable Bond Count5ChemAxon
Refractivity86.98 m3·mol-1ChemAxon
Polarizability25.88 Å3ChemAxon
Number of Rings1ChemAxon
Bioavailability1ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
Spectra
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, PositiveNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, PositiveNot Available
MSMass Spectrum (Electron Ionization)splash10-016u-6900000000-6488b097a4640e8af61aView in MoNA
References
Synthesis Reference

DrugSyn.org

US3520926
General ReferencesNot Available
External Links
ATC CodesL01XB01
AHFS Codes
  • 10:00.00
PDB EntriesNot Available
FDA labelNot Available
MSDSDownload (63.2 KB)
Interactions
Drug Interactions
Drug
AcepromazineThe risk or severity of adverse effects can be increased when Procarbazine is combined with Acepromazine.
AcetophenazineThe risk or severity of adverse effects can be increased when Procarbazine is combined with Acetophenazine.
AltretamineAltretamine may increase the orthostatic hypotensive activities of Procarbazine.
AmisulprideThe risk or severity of adverse effects can be increased when Procarbazine is combined with Amisulpride.
AmitriptylineProcarbazine may increase the serotonergic activities of Amitriptyline.
AmphetamineProcarbazine may increase the hypertensive activities of Amphetamine.
ApraclonidineThe risk or severity of adverse effects can be increased when Procarbazine is combined with Apraclonidine.
AripiprazoleThe risk or severity of adverse effects can be increased when Procarbazine is combined with Aripiprazole.
AtomoxetineProcarbazine may increase the central neurotoxic activities of Atomoxetine.
AtropineProcarbazine may increase the hypertensive activities of Atropine.
BenzquinamideThe risk or severity of adverse effects can be increased when Procarbazine is combined with Benzquinamide.
BetahistineThe serum concentration of Betahistine can be increased when it is combined with Procarbazine.
BezafibrateThe risk or severity of adverse effects can be increased when Procarbazine is combined with Bezafibrate.
BrimonidineThe risk or severity of adverse effects can be increased when Procarbazine is combined with Brimonidine.
BuprenorphineThe risk or severity of adverse effects can be increased when Buprenorphine is combined with Procarbazine.
BupropionProcarbazine may increase the hypertensive activities of Bupropion.
BuspironeThe risk or severity of adverse effects can be increased when Buspirone is combined with Procarbazine.
CarbamazepineThe risk or severity of adverse effects can be increased when Carbamazepine is combined with Procarbazine.
CarbocisteineThe risk or severity of adverse effects can be increased when Procarbazine is combined with Carbocisteine.
CarphenazineThe risk or severity of adverse effects can be increased when Procarbazine is combined with Carphenazine.
CathinoneProcarbazine may increase the hypertensive activities of Cathinone.
ChlormezanoneThe risk or severity of adverse effects can be increased when Procarbazine is combined with Chlormezanone.
ChlorpromazineThe risk or severity of adverse effects can be increased when Procarbazine is combined with Chlorpromazine.
ChlorprothixeneThe risk or severity of adverse effects can be increased when Procarbazine is combined with Chlorprothixene.
ClozapineThe risk or severity of adverse effects can be increased when Procarbazine is combined with Clozapine.
CyclobenzaprineCyclobenzaprine may increase the serotonergic activities of Procarbazine.
CyproheptadineProcarbazine may increase the anticholinergic activities of Cyproheptadine.
DapoxetineThe risk or severity of adverse effects can be increased when Dapoxetine is combined with Procarbazine.
DenosumabThe risk or severity of adverse effects can be increased when Denosumab is combined with Procarbazine.
DexmethylphenidateProcarbazine may increase the hypertensive activities of Dexmethylphenidate.
DextromethorphanProcarbazine may increase the serotonergic activities of Dextromethorphan.
DiethylpropionProcarbazine may increase the hypertensive activities of Diethylpropion.
DomperidoneThe risk or severity of adverse effects can be increased when Procarbazine is combined with Domperidone.
DoxapramProcarbazine may increase the hypertensive activities of Doxapram.
DroperidolThe risk or severity of adverse effects can be increased when Procarbazine is combined with Droperidol.
EpinephrineProcarbazine may increase the hypertensive activities of Epinephrine.
FencamfamineThe risk or severity of adverse effects can be increased when Procarbazine is combined with Fencamfamine.
FlupentixolThe risk or severity of adverse effects can be increased when Procarbazine is combined with Flupentixol.
FluphenazineThe risk or severity of adverse effects can be increased when Procarbazine is combined with Fluphenazine.
FluspirileneThe risk or severity of adverse effects can be increased when Procarbazine is combined with Fluspirilene.
FluvoxamineThe risk or severity of adverse effects can be increased when Fluvoxamine is combined with Procarbazine.
GranisetronGranisetron may increase the serotonergic activities of Procarbazine.
HaloperidolThe risk or severity of adverse effects can be increased when Procarbazine is combined with Haloperidol.
HydrocodoneThe risk or severity of adverse effects can be increased when Procarbazine is combined with Hydrocodone.
HydromorphoneThe risk or severity of adverse effects can be increased when Procarbazine is combined with Hydromorphone.
Insulin HumanProcarbazine may increase the hypoglycemic activities of Insulin Regular.
IsomethepteneThe risk or severity of adverse effects can be increased when Procarbazine is combined with Isometheptene.
L-TryptophanThe risk or severity of adverse effects can be increased when L-Tryptophan is combined with Procarbazine.
LeflunomideThe risk or severity of adverse effects can be increased when Procarbazine is combined with Leflunomide.
LevodopaThe risk or severity of adverse effects can be increased when Levodopa is combined with Procarbazine.
LevonordefrinProcarbazine may increase the hypertensive activities of Levonordefrin.
LinezolidThe risk or severity of adverse effects can be increased when Procarbazine is combined with Linezolid.
LithiumThe risk or severity of adverse effects can be increased when Procarbazine is combined with Lithium.
LoxapineThe risk or severity of adverse effects can be increased when Procarbazine is combined with Loxapine.
MaprotilineThe risk or severity of adverse effects can be increased when Maprotiline is combined with Procarbazine.
MequitazineProcarbazine may increase the anticholinergic activities of Mequitazine.
MesoridazineThe risk or severity of adverse effects can be increased when Procarbazine is combined with Mesoridazine.
MetamizoleThe risk or severity of adverse effects can be increased when Metamizole is combined with Procarbazine.
MethadoneThe risk or severity of adverse effects can be increased when Procarbazine is combined with Methadone.
MethotrimeprazineThe risk or severity of adverse effects can be increased when Procarbazine is combined with Methotrimeprazine.
MethyldopaThe risk or severity of adverse effects can be increased when Procarbazine is combined with Methyldopa.
Methylene blueProcarbazine may increase the serotonergic activities of Methylene blue.
MethylphenidateProcarbazine may increase the hypertensive activities of Methylphenidate.
MetoclopramideThe risk or severity of adverse effects can be increased when Procarbazine is combined with Metoclopramide.
MianserinProcarbazine may increase the neurotoxic activities of Mianserin.
MidodrineProcarbazine may increase the hypertensive activities of Midodrine.
MirtazapineProcarbazine may increase the central neurotoxic activities of Mirtazapine.
MoclobemideThe risk or severity of adverse effects can be increased when Procarbazine is combined with Moclobemide.
MolindoneThe risk or severity of adverse effects can be increased when Procarbazine is combined with Molindone.
MorphineThe risk or severity of adverse effects can be increased when Procarbazine is combined with Morphine.
MoxonidineProcarbazine may increase the hypotensive activities of Moxonidine.
NatalizumabThe risk or severity of adverse effects can be increased when Procarbazine is combined with Natalizumab.
NorepinephrineProcarbazine may increase the hypertensive activities of Norepinephrine.
OlanzapineThe risk or severity of adverse effects can be increased when Procarbazine is combined with Olanzapine.
OndansetronThe risk or severity of adverse effects can be increased when Procarbazine is combined with Ondansetron.
OrciprenalineThe risk or severity of adverse effects can be increased when Procarbazine is combined with Orciprenaline.
OxycodoneThe risk or severity of adverse effects can be increased when Procarbazine is combined with Oxycodone.
OxymorphoneThe risk or severity of adverse effects can be increased when Oxymorphone is combined with Procarbazine.
PaliperidoneThe risk or severity of adverse effects can be increased when Procarbazine is combined with Paliperidone.
ParoxetineProcarbazine may increase the serotonergic activities of Paroxetine.
PerphenazineThe risk or severity of adverse effects can be increased when Procarbazine is combined with Perphenazine.
PethidineProcarbazine may increase the serotonergic activities of Pethidine.
PhenelzinePhenelzine may increase the orthostatic hypotensive activities of Procarbazine.
PholcodinePholcodine may increase the serotonergic activities of Procarbazine.
PimecrolimusThe risk or severity of adverse effects can be increased when Pimecrolimus is combined with Procarbazine.
PimozideThe risk or severity of adverse effects can be increased when Procarbazine is combined with Pimozide.
PiperacetazineThe risk or severity of adverse effects can be increased when Procarbazine is combined with Piperacetazine.
PizotifenProcarbazine may increase the anticholinergic activities of Pizotifen.
ProchlorperazineThe risk or severity of adverse effects can be increased when Procarbazine is combined with Prochlorperazine.
PromazineThe risk or severity of adverse effects can be increased when Procarbazine is combined with Promazine.
QuetiapineThe risk or severity of adverse effects can be increased when Procarbazine is combined with Quetiapine.
RemoxiprideThe risk or severity of adverse effects can be increased when Procarbazine is combined with Remoxipride.
ReserpineThe risk or severity of adverse effects can be increased when Procarbazine is combined with Reserpine.
RisperidoneThe risk or severity of adverse effects can be increased when Procarbazine is combined with Risperidone.
RoflumilastRoflumilast may increase the immunosuppressive activities of Procarbazine.
SertindoleThe risk or severity of adverse effects can be increased when Procarbazine is combined with Sertindole.
Sipuleucel-TThe therapeutic efficacy of Sipuleucel-T can be decreased when used in combination with Procarbazine.
SufentanilSufentanil may increase the serotonergic activities of Procarbazine.
SulpirideThe risk or severity of adverse effects can be increased when Procarbazine is combined with Sulpiride.
TacrolimusThe risk or severity of adverse effects can be increased when Tacrolimus is combined with Procarbazine.
TapentadolThe risk or severity of adverse effects can be increased when Tapentadol is combined with Procarbazine.
Tedizolid PhosphateTedizolid Phosphate may increase the serotonergic activities of Procarbazine.
TetrabenazineThe risk or severity of adverse effects can be increased when Tetrabenazine is combined with Procarbazine.
TetryzolineProcarbazine may increase the hypertensive activities of Tetryzoline.
ThioridazineThe risk or severity of adverse effects can be increased when Procarbazine is combined with Thioridazine.
ThiothixeneThe risk or severity of adverse effects can be increased when Procarbazine is combined with Thiothixene.
TianeptineThe risk or severity of adverse effects can be increased when Tianeptine is combined with Procarbazine.
TofacitinibProcarbazine may increase the immunosuppressive activities of Tofacitinib.
TolcaponeThe risk or severity of adverse effects can be increased when Tolcapone is combined with Procarbazine.
TramadolTramadol may increase the neuroexcitatory activities of Procarbazine.
TranylcypromineTranylcypromine may increase the orthostatic hypotensive activities of Procarbazine.
TrastuzumabTrastuzumab may increase the neutropenic activities of Procarbazine.
TrazodoneThe risk or severity of adverse effects can be increased when Procarbazine is combined with Trazodone.
TrifluoperazineThe risk or severity of adverse effects can be increased when Procarbazine is combined with Trifluoperazine.
TriflupromazineThe risk or severity of adverse effects can be increased when Procarbazine is combined with Triflupromazine.
VenlafaxineProcarbazine may increase the serotonergic activities of Venlafaxine.
ZiprasidoneThe risk or severity of adverse effects can be increased when Procarbazine is combined with Ziprasidone.
ZuclopenthixolThe risk or severity of adverse effects can be increased when Procarbazine is combined with Zuclopenthixol.
Food InteractionsNot Available

Targets

1. DNA
Kind
Nucleotide
Organism
Human
Pharmacological action
yes
Actions
cross-linking/alkylation
General Function:
Used for biological information storage.
Specific Function:
DNA contains the instructions needed for an organism to develop, survive and reproduce.
Molecular Weight:
2.15 x 1012 Da
References
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [PubMed:17139284 ]
  2. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [PubMed:17016423 ]
  3. Ogawa K, Hiraku Y, Oikawa S, Murata M, Sugimura Y, Kawamura J, Kawanishi S: Molecular mechanisms of DNA damage induced by procarbazine in the presence of Cu(II). Mutat Res. 2003 Aug 5;539(1-2):145-55. [PubMed:12948823 ]
  4. Kyrtopoulos SA, Anderson LM, Chhabra SK, Souliotis VL, Pletsa V, Valavanis C, Georgiadis P: DNA adducts and the mechanism of carcinogenesis and cytotoxicity of methylating agents of environmental and clinical significance. Cancer Detect Prev. 1997;21(5):391-405. [PubMed:9307842 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
General Function:
Xanthine oxidase activity
Specific Function:
Key enzyme in purine degradation. Catalyzes the oxidation of hypoxanthine to xanthine. Catalyzes the oxidation of xanthine to uric acid. Contributes to the generation of reactive oxygen species. Has also low oxidase activity towards aldehydes (in vitro).
Gene Name:
XDH
Uniprot ID:
P47989
Molecular Weight:
146422.99 Da
Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
substrate
General Function:
Oxygen binding
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 unrelated compounds, including steroids, fatty acids, retinoid and xenobiotics. Preferentially oxidizes 17beta-estradiol to the carcinogenic 4-hydroxy derivative, and a variety of procarcinogenic compou...
Gene Name:
CYP1B1
Uniprot ID:
Q16678
Molecular Weight:
60845.33 Da
References
  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. doi: 10.1093/nar/gkp970. Epub 2009 Nov 24. [PubMed:19934256 ]
Comments
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Drug created on June 13, 2005 07:24 / Updated on October 08, 2013 14:25