Procarbazine

Procarbazine
Clinical data


Trade names	Matulane, Natulan, Indicarb
AHFS/Drugs.com	Monograph
MedlinePlus	a682094
Pregnancy category	AU: D US: D (Evidence of risk)
Routes of administration	By mouth (gel capsule), intravenous
ATC code	L01XB01 (WHO)
Legal status
Legal status	℞ (Prescription only)
Pharmacokinetic data
Metabolism	Hepatic, Renal
Biological half-life	10 minutes
Excretion	Renal
Identifiers
IUPAC name N-Isopropyl-4-[(2-methylhydrazino)methyl]benzamide
CAS Number	671-16-9^Y
PubChem (CID)	4915
IUPHAR/BPS	7278
DrugBank	DB01168^Y
ChemSpider	4746^Y
UNII	35S93Y190K^Y
KEGG	D08423^Y
ChEBI	CHEBI:71417^N
ChEMBL	CHEMBL1321^Y
ECHA InfoCard	100.010.531
Chemical and physical data
Formula	C₁₂H₁₉N₃O
Molar mass	221.299 g/mol
3D model (Jmol)	Interactive image
SMILES O=C(c1ccc(cc1)CNNC)NC(C)C
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)^Y Key:CPTBDICYNRMXFX-UHFFFAOYSA-N^Y
^NY (what is this?) (verify)

Procarbazine is a chemotherapy medication for the treatment of Hodgkin's lymphoma and certain brain cancers (such as glioblastoma multiforme).

It is a member of a group of medicines called alkylating agents. The drug is metabolized and activated in the liver. It also inhibits MAO thus increasing the effects of sympathomimetics, TCAs, and tyramine.

It gained FDA Approved in July 1969. It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.^[1]

Medical uses

When used to treat Hodgkin's lymphoma, it is often delivered as part of the BEACOPP regimen that includes bleomycin, etoposide, adriamycin, cyclophosphamide, vincristine (tradename Oncovin), prednisone, and procarbazine. The first combination chemotherapy developed for Hodgkin's lymphoma (HL), MOPP also included procarbazine (ABVD has supplanted MOPP as standard first line treatment for HL, with BEACOPP as an alternative for advanced/unfavorable HL). Alternatively, when used to treat certain brain tumors (malignant gliomas), it is often dosed as PCV when combined with lomustine (often called CCNU) and vincristine.

Side effects

When combined with ethanol, procarbazine may cause a disulfiram-like reaction in some patients. It also inhibits the liver's CYP450 microsomal system, which leads to an increased effect of barbiturates, phenothiazenes, and narcotics normally metabolized by the CYP450 enzymes. Has monamine oxidase inhibition properties (MAOI), and should not be taken with most antidepressants and certain migraine medications.

Inhibits MAO in the gastrointestinal system thus can cause hypertensive crises if associated with the ingestion of tyramine-rich foods such as aged cheeses.

Procarbazine rarely causes chemotherapy-induced peripheral neuropathy,^[2] a progressive, enduring, often irreversible tingling numbness, intense pain, and hypersensitivity to cold, beginning in the hands and feet and sometimes involving the arms and legs.^[3]

Pharmacology

Its mechanism of action is not fully understood. Metabolism yields azo-procarbazine and hydrogen peroxide which results in the breaking of DNA strands.

Dose

Dose should be adjusted for renal (kidney) disease or hepatic (liver) disease.

References

↑ "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014.
↑ Lisa M. DeAngelis; Jerome B. Posner (2003). "Nonmetastatic Complications". In Kufe DW; Pollock RE; Weichselbaum RR; et al. Holland-Frei Cancer Medicine (6th ed.). Hamilton (ON): BC Decker.
↑ del Pino BM. Chemotherapy-induced Peripheral Neuropathy. NCI Cancer Bulletin. Feb 23, 2010;7(4):6.

External links

Intracellular chemotherapeutic agents / antineoplastic agents (L01)

SPs/MIs
(M phase)

Block microtubule assembly	Vinca alkaloids (Vinblastine^# Vincristine^# Vinflunine^§ Vindesine Vinorelbine)

Block microtubule disassembly	Taxanes (Cabazitaxel Docetaxel^# Larotaxel Ortataxel^† Paclitaxel^# Tesetaxel) Epothilones (Ixabepilone)

DNA replication
inhibitor

DNA precursors/
antimetabolites
(S phase)

Folic acid	Dihydrofolate reductase inhibitor (Aminopterin Methotrexate^# Pemetrexed Pralatrexate) Thymidylate synthase inhibitor (Raltitrexed Pemetrexed)

Purine	Adenosine deaminase inhibitor (Pentostatin) Halogenated/ribonucleotide reductase inhibitors (Cladribine Clofarabine Fludarabine) Nelarabine Thiopurine (Thioguanine^# Mercaptopurine^#)

Pyrimidine	Thymidylate synthase inhibitor (Fluorouracil^# Capecitabine Tegafur (+gimeracil/oteracil) Carmofur Floxuridine) DNA polymerase inhibitor (Cytarabine^#) Ribonucleotide reductase inhibitor (Gemcitabine) Hypomethylating agent (Azacitidine Decitabine)

Deoxyribonucleotide	Ribonucleotide reductase inhibitor (Hydroxycarbamide)

Topoisomerase inhibitors
(S phase)

I	Camptotheca (Camptothecin Cositecan^† Belotecan Gimatecan Exatecan Irinotecan Lurtotecan^‡ Silatecan^§ Topotecan Rubitecan^‡)

II	Podophyllum (Etoposide^# Teniposide)

II+Intercalation	Anthracyclines (Aclarubicin Daunorubicin^# Doxorubicin^# Epirubicin Idarubicin Amrubicin^† Pirarubicin Valrubicin Zorubicin) Anthracenediones (Mitoxantrone Pixantrone)

Crosslinking of DNA
(CCNS)

Alkylating	Nitrogen mustards: Mechlorethamine Cyclophosphamide^# (Ifosfamide Trofosfamide) Chlorambucil^# (Melphalan Prednimustine) Bendamustine Uramustine Estramustine Nitrosoureas: Carmustine Lomustine (Semustine) Fotemustine Nimustine Ranimustine Streptozocin Alkyl sulfonates: Busulfan (Mannosulfan Treosulfan) Aziridines: Carboquone ThioTEPA Triaziquone Triethylenemelamine

Platinum-based	Carboplatin Cisplatin Dicycloplatin Nedaplatin Oxaliplatin Satraplatin

Nonclassical	Hydrazines (Procarbazine^#) Triazenes (Dacarbazine^# Temozolomide) Altretamine Mitobronitol Pipobroman

Intercalation	Streptomyces (Actinomycin^# Bleomycin^# Mitomycin Plicamycin)

Photosensitizers/PDT

Other

Enzyme inhibitors	FI (Tipifarnib^§) CDK inhibitors (Alvocidib^† Seliciclib^† Palbociclib) PrI Bortezomib Carfilzomib Ixazomib PhI (Anagrelide) IMPDI (Tiazofurin^§) LI (Masoprocol) PARP inhibitor (Olaparib) HDAC (Belinostat Panobinostat Romidepsin Vorinostat) PIKI (Idelalisib)

Receptor antagonists	ERA (Atrasentan) Retinoid X receptor (Bexarotene) Sex steroid (Testolactone)

Other/ungrouped	Amsacrine Trabectedin Retinoids (Alitretinoin Tretinoin) Arsenic trioxide Asparagine depleters (Asparaginase^#/Pegaspargase) Celecoxib Demecolcine Elesclomol^§ Elsamitrucin Etoglucid Lonidamine Lucanthone Mitoguazone Mitotane Oblimersen^† Omacetaxine mepesuccinate Eribulin

^#WHO-EM
^‡Withdrawn from market
Clinical trials:
- ^†Phase III
- ^§Never to phase III

Monoamine metabolism modulators

Common
(non-specific)

AAAD

MAO

Inhibitors: Non-selective: Benmoxin Caroxazone Echinopsidine Furazolidone Guineesine Hydralazine Indantadol Iproclozide Iproniazid Isocarboxazid Isoniazid Linezolid Mebanazine Metfendrazine Nialamide Octamoxin Paraxazone Phenelzine Pheniprazine Phenoxypropazine Pivhydrazine Procarbazine Safrazine Tranylcypromine

Inhibitors: MAO-A-selective: Amiflamine Bazinaprine Befloxatone Brofaromine Cimoxatone Clorgiline CX157 (Tyrima) Eprobemide Esuprone Harmala alkaloids (e.g., harmine, harmaline, harman, norharman, tetrahydroharmine) Methylene blue Metralindole Minaprine Moclobemide Pirlindole Sercloremine Tetrindole Toloxatone

Inhibitors: MAO-B selective: Almoxatone D-Deprenyl Ethanol Ladostigil Lazabemide Milacemide Mofegiline Nicotine Pargyline^‡ Rasagiline Safinamide Selegiline (L-Deprenyl)

Phenethylamines
(dopamine, epinephrine,
norepinephrine)

PAH	Inhibitors: 3,4-Dihydroxystyrene

TH	Inhibitors: 2-Hydroxyestradiol 2-Hydroxyestrone 3-Iodotyrosine Aquayamycin Bulbocapnine Metirosine Oudenone

DBH	Inhibitors: Bupicomide Disulfiram Dopastin Fusaric acid Nepicastat Phenopicolinic acid Tropolone

PNMT	Inhibitors: CGS-19281A SKF-64139 SKF-7698

COMT	Inhibitors: 2-Hydroxyestradiol 2-Hydroxyestrone Entacapone Nitecapone Tolcapone

Tryptamines
(serotonin, melatonin)

TPH	Inhibitors: AGN-2979 Fenclonine (PCPA) Telotristat

See also: Adrenergics • Dopaminergics • Melatonergics • Serotonergics • Monoamine reuptake and release modulators • Monoamine neurotoxins

Hydrazines

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