Procarbazine is an antineoplastic agent indicated for the treatment of stage III and stage IV Hodgkin's disease in combination with other chemotherapeutic agents.
- Brand Names
- Generic Name
- DrugBank Accession Number
An antineoplastic agent used primarily in combination with mechlorethamine, vincristine, and prednisone (the MOPP protocol) in the treatment of Hodgkin's disease.
- Small Molecule
- Approved, Investigational
- 3DSimilar Structures
- Average: 221.2988
- Chemical Formula
- External IDs
For use with other anticancer drugs for the treatment of stage III and stage IV Hodgkin's disease.Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.
- Associated Conditions
- Contraindications & Blackbox Warnings
- Avoid life-threatening adverse drug eventsImprove clinical decision support with information on contraindications & blackbox warnings, population restrictions, harmful risks, & more.Avoid life-threatening adverse drug events & improve clinical decision support.
Procarbazine 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 action
The 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.
Target Actions Organism AMonoamine oxidaseinhibitor Humans ADNAcross-linking/alkylation Humans
Procarbazine is rapidly and completely absorbed.
- Volume of distribution
- Protein binding
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.
Hover over products below to view reaction partners
- Route of elimination
- Adverse Effects
- Improve decision support & research outcomesWith structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.Improve decision support & research outcomes with our structured adverse effects data.
LD50=785 mg/kg (orally in rats)
- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug InteractionIntegrate drug-drug
interactions in your software
1,2-Benzodiazepine The risk or severity of adverse effects can be increased when Procarbazine is combined with 1,2-Benzodiazepine. Abaloparatide Procarbazine may increase the orthostatic hypotensive activities of Abaloparatide. Abatacept The risk or severity of adverse effects can be increased when Procarbazine is combined with Abatacept. Abciximab The risk or severity of bleeding and hemorrhage can be increased when Procarbazine is combined with Abciximab. Acarbose Procarbazine may increase the hypoglycemic activities of Acarbose. Acebutolol Procarbazine may increase the hypotensive activities of Acebutolol. Acenocoumarol The risk or severity of bleeding and hemorrhage can be increased when Procarbazine is combined with Acenocoumarol. Acetazolamide The risk or severity of adverse effects can be increased when Acetazolamide is combined with Procarbazine. Acetohexamide Procarbazine may increase the hypoglycemic activities of Acetohexamide. Acetophenazine The risk or severity of extrapyramidal symptoms can be increased when Procarbazine is combined with Acetophenazine.Identify potential medication risksEasily compare up to 40 drugs with our drug interaction checker.Get severity rating, description, and management advice.Learn more
- Food Interactions
- Avoid alcohol. Ingesting alcohol may potentiate the CNS depressant effects of procarbazine and may precipitate a disulfiram-like-reaction (nausea, flushing).
- Avoid tyramine-containing foods and supplements. Foods that contain tyramine include yogurt, aged cheese, ripe bananas, wine, and sourdough bread.
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Product Ingredients
Ingredient UNII CAS InChI Key Procarbazine hydrochloride XH0NPH5ZX8 366-70-1 OCSSHHHAHMCFDV-UHFFFAOYSA-N
- International/Other Brands
- Indicarb / Natulan
- Brand Name Prescription Products
Name Dosage Strength Route Labeller Marketing Start Marketing End Region Image Matulane Capsule 50 mg/1 Oral Sigma-Tau Pharmaceuticals, Inc. 1985-12-27 2020-03-31 Matulane Capsule 50 mg/1 Oral Leadiant Biosciences, Inc. 1985-12-27 Not applicable Matulane Capsule 50 mg Oral Leadiant Biosciences, Inc 1970-12-31 Not applicable
- ATC Codes
- L01XB01 — Procarbazine
- Drug Categories
- Acids, Carbocyclic
- Agents Causing Muscle Toxicity
- Alkylating Activity
- Alkylating Drugs
- Antidepressive Agents
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- Benzamides and benzamide derivatives
- Benzene Derivatives
- Central Nervous System Depressants
- Immunosuppressive Agents
- Monoamine Oxidase Inhibitors
- Myelosuppressive Agents
- Narrow Therapeutic Index Drugs
- Serotonergic Drugs Shown to Increase Risk of Serotonin Syndrome
- Serotonin Agents
- Serotonin Modulators
- Chemical TaxonomyProvided by Classyfire
- This compound belongs to the class of organic compounds known as benzamides. These are organic compounds containing a carboxamido substituent attached to a benzene ring.
- Organic compounds
- Super Class
- Benzene and substituted derivatives
- Sub Class
- Benzoic acids and derivatives
- Direct Parent
- Alternative Parents
- Benzoyl derivatives / Secondary carboxylic acid amides / Alkylhydrazines / Organopnictogen compounds / Organooxygen compounds / Organic oxides / Hydrocarbon derivatives
- Alkylhydrazine / Aromatic homomonocyclic compound / Benzamide / Benzoyl / Carboxamide group / Carboxylic acid derivative / Hydrazine derivative / Hydrocarbon derivative / Organic nitrogen compound / Organic oxide
- Molecular Framework
- Aromatic homomonocyclic compounds
- External Descriptors
- benzamides, hydrazines (CHEBI:71417)
- Affected organisms
- Humans and other mammals
- CAS number
- InChI Key
- IUPAC Name
- Synthesis Reference
- General References
- Not Available
- External Links
- Human Metabolome Database
- KEGG Drug
- KEGG Compound
- PubChem Compound
- PubChem Substance
- Therapeutic Targets Database
- RxList Drug Page
- Drugs.com Drug Page
- Download (63.2 KB)
- Clinical Trials
Phase Status Purpose Conditions Count 3 Active Not Recruiting Treatment Lymphoma 5 3 Completed Treatment Advanced Hodgkin Disease 1 3 Completed Treatment Brain Neoplasm / Central Nervous System Neoplasm 1 3 Completed Treatment Central Nervous System Neoplasm 4 3 Completed Treatment Hodgkin's Lymphoma 5 3 Completed Treatment Lymphoma 4 3 Not Yet Recruiting Treatment Classical Hodgkin's Lymphoma 1 3 Recruiting Treatment Central Nervous System Neoplasm 1 3 Recruiting Treatment Classical Hodgkin's Lymphoma 1 3 Recruiting Treatment Oligodendroglioma 1
- Not Available
- AAIPharma Inc.
- B&B Pharmaceuticals
- Kaiser Foundation Hospital
- Sigma-Tau Pharmaceuticals Inc.
- Dosage Forms
Form Route Strength Capsule Oral 50 mg/1 Capsule Oral 50 mg
Unit description Cost Unit Matulane 50 mg capsule 55.68USD capsuleDrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
- Not Available
- Experimental Properties
Property Value Source melting point (°C) 223 °C Not Available water solubility 1420 mg/L Not Available logP 0.06 HANSCH,C ET AL. (1995)
- Predicted Properties
Property Value Source Water Solubility 0.228 mg/mL ALOGPS logP 0.53 ALOGPS logP 0.99 Chemaxon logS -3 ALOGPS pKa (Strongest Acidic) 15.03 Chemaxon pKa (Strongest Basic) 5.56 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 3 Chemaxon Polar Surface Area 53.16 Å2 Chemaxon Rotatable Bond Count 5 Chemaxon Refractivity 86.98 m3·mol-1 Chemaxon Polarizability 25.88 Å3 Chemaxon Number of Rings 1 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon
- Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 0.9954 Blood Brain Barrier + 0.9855 Caco-2 permeable + 0.6013 P-glycoprotein substrate Non-substrate 0.5748 P-glycoprotein inhibitor I Non-inhibitor 0.8839 P-glycoprotein inhibitor II Non-inhibitor 0.9771 Renal organic cation transporter Non-inhibitor 0.7974 CYP450 2C9 substrate Non-substrate 0.8293 CYP450 2D6 substrate Non-substrate 0.702 CYP450 3A4 substrate Non-substrate 0.5484 CYP450 1A2 substrate Inhibitor 0.9107 CYP450 2C9 inhibitor Non-inhibitor 0.9071 CYP450 2D6 inhibitor Non-inhibitor 0.9231 CYP450 2C19 inhibitor Inhibitor 0.8994 CYP450 3A4 inhibitor Non-inhibitor 0.8308 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9414 Ames test Non AMES toxic 0.9132 Carcinogenicity Carcinogens 0.6428 Biodegradation Not ready biodegradable 0.9741 Rat acute toxicity 2.4348 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9785 hERG inhibition (predictor II) Non-inhibitor 0.9287
- Mass Spec (NIST)
- Not Available
Spectrum Spectrum Type Splash Key Predicted GC-MS Spectrum - GC-MS Predicted GC-MS Not Available Mass Spectrum (Electron Ionization) MS splash10-016u-6900000000-6488b097a4640e8af61a Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available MS/MS Spectrum - , positive LC-MS/MS splash10-0096-0910000000-161c214dc9eb9c75895b
- Protein group
- Pharmacological action
- General Function
- Serotonin binding
- 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...
- Holt A, Sharman DF, Callingham BA, Kettler R: Characteristics of procarbazine as an inhibitor in-vitro of rat semicarbazide-sensitive amine oxidase. J Pharm Pharmacol. 1992 Jun;44(6):487-93. [Article]
- Kraft SL, Baker NM, Carpenter J, Bostwick JR: Procarbazine and antidepressants: a retrospective review of the risk of serotonin toxicity. Psychooncology. 2014 Jan;23(1):108-13. doi: 10.1002/pon.3378. Epub 2013 Aug 29. [Article]
- Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. [Article]
- 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. [Article]
- 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. [Article]
- 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. [Article]
- Pharmacological action
- 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. Ha...
- Gene Name
- Uniprot ID
- Uniprot Name
- Xanthine dehydrogenase/oxidase
- Molecular Weight
- 146422.99 Da
- Tweedie DJ, Fernandez D, Spearman ME, Feldhoff RC, Prough RA: Metabolism of azoxy derivatives of procarbazine by aldehyde dehydrogenase and xanthine oxidase. Drug Metab Dispos. 1991 Jul-Aug;19(4):793-803. [Article]
Drug created at June 13, 2005 13:24 / Updated at March 22, 2023 23:54