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Details

Stereochemistry ACHIRAL
Molecular Formula C5H5N3O
Molecular Weight 123.1127
Optical Activity UNSPECIFIED
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of PYRAZINAMIDE

SMILES

NC(=O)C1=CN=CC=N1

InChI

InChIKey=IPEHBUMCGVEMRF-UHFFFAOYSA-N
InChI=1S/C5H5N3O/c6-5(9)4-3-7-1-2-8-4/h1-3H,(H2,6,9)

HIDE SMILES / InChI

Description

Pyrazinamide is indicated for the initial treatment of active tuberculosis in adults and children when combined with other antituberculous agents. (The current recommendation of the CDC for drug-susceptible disease is to use a six-month regimen for initial treatment of active tuberculosis, consisting of isoniazid, rifampin and pyrazinamide given for 2 months, followed by isoniazid and rifampin for 4 months. Pyrazinamide should only be used in conjunction with other effective antituberculous agents. Pyrazinamide diffuses into M. tuberculosis, where the enzyme pyrazinamidase converts pyrazinamide to the active form pyrazinoic acid. Under acidic conditions, the pyrazinoic acid that slowly leaks out converts to the protonated conjugate acid, which is thought to diffuse easily back into the bacilli and accumulate. The net effect is that more pyrazinoic acid accumulates inside the bacillus at acid pH than at neutral pH. Pyrazinoic acid was thought to inhibit the enzyme fatty acid synthase (FAS) I, which is required by the bacterium to synthesise fatty acids. However, this theory was thought to have been discounted. However, further studies reproduced the results of FAS I inhibition as the putative mechanism first in whole cell assay of replicating M. tuberculosis bacilli which have shown that pyrazinoic acid and its ester inhibit the synthesis of fatty acids . This study was followed by in vitro assay of tuberculous FAS I enzyme that tested the activity with pyrazinamide, pyrazinoic acid and several classes of pyrazinamide analogs. Pyrazinamide and its analogs inhibited the activity of purified FAS I. It has also been suggested that the accumulation of pyrazinoic acid disrupts membrane potential and interferes with energy production, necessary for survival of M. tuberculosis at an acidic site of infection. Pyrazinoic acid has also been shown to bind to the ribosomal protein S1 (RpsA) and inhibit trans-translation. This may explain the ability of the drug to kill dormant mycobacteria

CNS Activity

Originator

Approval Year

Targets

Targets

Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
PYRAZINAMIDE
PubMed

PubMed

TitleDatePubMed
Serial counts of Mycobacterium tuberculosis in sputum as surrogate markers of the sterilising activity of rifampicin and pyrazinamide in treating pulmonary tuberculosis.
2001
The molecular basis of resistance to isoniazid, rifampin, and pyrazinamide in Mycobacterium tuberculosis.
2001
[Effectiveness of chemotherapy of intrathoracic tuberculosis in children: late follow-up data].
2001
Pancreatic mass caused by Mycobacterium tuberculosis with reduced drug sensitivity.
2001 Apr
[Functional role of the red nucleus in the cerebral cortex-cerebellum-spinal cord communication system].
2001 Apr-Jun
Renal handling of uric acid assessed by means of pharmacological tests in obese women.
2001 Aug
Rifampicin allergy confirmed by an intradermal test, but with a negative patch test.
2001 Aug
Tubercular laryngeal abscess.
2001 Aug
Childhood and adolescent tuberculosis in northern Taiwan: an institutional experience during 1994-1999.
2001 Aug
Can serial qualitative polymerase chain reaction monitoring predict outcome of pulmonary tuberculosis treatment?
2001 Dec
[Treatment outcomes of multidrug-resistant tuberculosis--comparison between success and failure cases].
2001 Dec
Isonicotinic acid hydrazide induced anagen effluvium and associated lichenoid eruption.
2001 Dec
Pyrazinamide use as a method of estimating under-reporting of tuberculosis.
2001 Dec
Side effects of antituberculosis treatment.
2001 Dec
Postantibiotic effects of antituberculosis agents alone and in combination.
2001 Dec
New mutations in pncA of in vitro selected pyrazinamide-resistant strains of Mycobacterium tuberculosis.
2001 Fall
Pattern of some haematological indices in newly diagnosed pulmonary tuberculosis cases in Iwo, Nigeria: diagnostic and therapeutic implications.
2001 Jan-Mar
Reintroducing antituberculosis therapy after Stevens-Johnson syndrome in human immunodeficiency virus-infected patients with tuberculosis: role of desensitization.
2001 Jul
[Multiple intracranial tuberculomas in infancy].
2001 Jul 1-15
Tuberculosis and HIV infection: epidemiology, immunology, and treatment.
2001 Jul-Aug
[Two cases of exercise-induced acute renal failure with idiopathic renal hypouricemia].
2001 May
Antimycobacterial plant terpenoids.
2001 Nov
Pyrazinamide induced photoallergy.
2001 Nov
Tuberculous meningitis: is a 6-month treatment regimen sufficient?
2001 Nov
Tuberculosis infection in Chinese patients undergoing continuous ambulatory peritoneal dialysis.
2001 Nov
Rapamycin and less immunosuppressive analogs are toxic to Candida albicans and Cryptococcus neoformans via FKBP12-dependent inhibition of TOR.
2001 Nov
Crystal structure and mechanism of catalysis of a pyrazinamidase from Pyrococcus horikoshii.
2001 Nov 27
[Orchiectomy for tuberculous epididymitis: a report of two cases with intractable to antituberculosis treatment].
2001 Oct
Characterization of pncA mutations of pyrazinamide-resistant Mycobacterium tuberculosis in Korea.
2001 Oct
Characterisation of the pncA gene in Mycobacterium tuberculosis isolates from Gauteng, South Africa.
2001 Oct
Treatment of tuberculosis in Haiti.
2001 Oct
Hepatotoxicity from rifampin plus pyrazinamide: lessons for policymakers and messages for care providers.
2001 Oct 1
Antitubercular drugs (isoniazid, rifampin and pyrazinamide): hepatobiliary reactions.
2001 Oct 2
[Vesical uric acid lithiasis in a child with renal hypouricemia].
2001 Sep
Safety of an ofloxacin-based antitubercular regimen for the treatment of tuberculosis in patients with underlying chronic liver disease: a preliminary report.
2001 Sep
Intramedullary tuberculoma of the conus medullaris: case report and review of the literature.
2001 Sep
Modulating effect of Liv.100, an ayurvedic formulation on antituberculosis drug-induced alterations in rat liver microsomes.
2001 Sep
Tuberculosis: guidelines changed for latent TB treatment.
2001 Sep 21
From the Centers for Disease Control and Prevention. Update: Fatal and severe liver injuries associated with Rifampin and Pyrazinamide for latent tuberculosis infection, and revisions in American Thoracic Society/CDC recommendations--United States, 2001.
2001 Sep 26
US guidelines for treatment of latent tuberculosis revised.
2001 Sep 8
Treatment of childhood tuberculosis with a six month directly observed regimen of only two weeks of daily therapy.
2002 Feb
Tuberculosis presenting as immune thrombocytopenic purpura.
2002 Feb
Conditions that may affect the results of susceptibility testing of Mycobacterium tuberculosis to pyrazinamide.
2002 Jan
Susceptibility testing of Mycobacterium tuberculosis to pyrazinamide.
2002 Jan
High rates of tuberculosis in end-stage renal failure: the impact of international migration.
2002 Jan
Surveillance for antimicrobial resistance in Croatia.
2002 Jan
Rapidly progressive glomerulonephritis due to rifampicin therapy.
2002 Jan
Liquid chromatographic determination of isoniazid, pyrazinamide and rifampicin from pharmaceutical preparations and blood.
2002 Jan 25
Therapeutic isoniazid monitoring using a simple high-performance liquid chromatographic method with ultraviolet detection.
2002 Jan 5
Tuberculoma of the conus medullaris: case report.
2002 Mar
Patents

Patents

Sample Use Guides

In Vivo Use Guide
15 to 30 mg/kg once daily
Route of Administration: Oral
Name Type Language
PYRAZINAMIDE
EP   HSDB   INN   MART.   MI   ORANGE BOOK   USP   USP-RS   VANDF   WHO-DD   WHO-IP  
INN  
Official Name English
PYRAZINAMIDE [USP-RS]
Common Name English
D-50
Code English
PYRAZIDE
Common Name English
PYRAZINAMIDE [MART.]
Common Name English
PYRAZINAMIDE COMPONENT OF RIFATER
Common Name English
PYRAZINAMIDE [HSDB]
Common Name English
PYRAZINAMIDE [EP]
Common Name English
PYRAFAT
Common Name English
PYRAMIZADE
Common Name English
PIRAZINAMID
Common Name English
PYRAZINAMIDE [MI]
Common Name English
RIFATER COMPONENT PYRAZINAMIDE
Common Name English
PYRAZINECARBOXAMIDE
Systematic Name English
ZINAMIDE
Common Name English
ALDINAMID
Common Name English
NOVAMID
Common Name English
PYRAZINAMIDE [VANDF]
Common Name English
ALDINAMIDE
Common Name English
FARMIZINA
Common Name English
NSC-14911
Code English
PYRAZINAMIDE [USP]
Common Name English
PYRAZINAMIDE [INN]
Common Name English
PYRAZINAMIDE [ORANGE BOOK]
Common Name English
UNIPYRANAMIDE
Common Name English
PIRAZIMIDA
Common Name English
PYRAZINAMIDUM [WHO-IP LATIN]
Common Name English
MK-56
Code English
PYRAZINE CARBOXYLAMIDE
Common Name English
.ALPHA.-PYRAZINAMIDE
Common Name English
ISOPAS
Common Name English
PYRAZINAMIDE [JAN]
Common Name English
PYRAZINAMIDE [WHO-DD]
Common Name English
PYRAZINAMIDE [WHO-IP]
Common Name English
ROZIDE
Common Name English
TEBRAZID
Common Name English
EPRAZIN
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C280
Created by admin on Mon Oct 21 19:47:24 UTC 2019 , Edited by admin on Mon Oct 21 19:47:24 UTC 2019
WHO-VATC QJ04AM05
Created by admin on Mon Oct 21 19:47:24 UTC 2019 , Edited by admin on Mon Oct 21 19:47:24 UTC 2019
WHO-ESSENTIAL MEDICINES LIST 6.2.4 (ISO/PYR/RIF)
Created by admin on Mon Oct 21 19:47:24 UTC 2019 , Edited by admin on Mon Oct 21 19:47:24 UTC 2019
WHO-ATC J04AM06
Created by admin on Mon Oct 21 19:47:24 UTC 2019 , Edited by admin on Mon Oct 21 19:47:24 UTC 2019
WHO-ATC J04AK01
Created by admin on Mon Oct 21 19:47:24 UTC 2019 , Edited by admin on Mon Oct 21 19:47:24 UTC 2019
WHO-ATC J04AM05
Created by admin on Mon Oct 21 19:47:24 UTC 2019 , Edited by admin on Mon Oct 21 19:47:24 UTC 2019
WHO-ESSENTIAL MEDICINES LIST 6.2.4 (ETH/ISO/PYR/RIF)
Created by admin on Mon Oct 21 19:47:24 UTC 2019 , Edited by admin on Mon Oct 21 19:47:24 UTC 2019
WHO-ESSENTIAL MEDICINES LIST 6.2.4
Created by admin on Mon Oct 21 19:47:24 UTC 2019 , Edited by admin on Mon Oct 21 19:47:24 UTC 2019
WHO-VATC QJ04AM06
Created by admin on Mon Oct 21 19:47:24 UTC 2019 , Edited by admin on Mon Oct 21 19:47:24 UTC 2019
LIVERTOX 817
Created by admin on Mon Oct 21 19:47:24 UTC 2019 , Edited by admin on Mon Oct 21 19:47:24 UTC 2019
NDF-RT N0000175483
Created by admin on Mon Oct 21 19:47:24 UTC 2019 , Edited by admin on Mon Oct 21 19:47:24 UTC 2019
WHO-VATC QJ04AK01
Created by admin on Mon Oct 21 19:47:24 UTC 2019 , Edited by admin on Mon Oct 21 19:47:24 UTC 2019
FDA ORPHAN DRUG 6585
Created by admin on Mon Oct 21 19:47:24 UTC 2019 , Edited by admin on Mon Oct 21 19:47:24 UTC 2019
Code System Code Type Description
EPA CompTox
98-96-4
Created by admin on Mon Oct 21 19:47:24 UTC 2019 , Edited by admin on Mon Oct 21 19:47:24 UTC 2019
PRIMARY
ChEMBL
CHEMBL614
Created by admin on Mon Oct 21 19:47:24 UTC 2019 , Edited by admin on Mon Oct 21 19:47:24 UTC 2019
PRIMARY
WIKIPEDIA
PYRAZINAMIDE
Created by admin on Mon Oct 21 19:47:24 UTC 2019 , Edited by admin on Mon Oct 21 19:47:24 UTC 2019
PRIMARY
WHO INTERNATIONAL PHARMACOPEIA
PYRAZINAMIDE
Created by admin on Mon Oct 21 19:47:24 UTC 2019 , Edited by admin on Mon Oct 21 19:47:24 UTC 2019
PRIMARY Description: A white or almost white, crystalline powder; odourless. Solubility: Sparingly soluble in water; slightly soluble in ethanol (~750 g/l) TS. Category: Antituberculosis drug. Storage: Pyrazinamide should be kept in a well-closed container. Definition: Pyrazinamide contains not less than 98.5% and not more than 101.0% of C5H5N3O, calculated with reference to the anhydrous substance.
ECHA (EC/EINECS)
202-717-6
Created by admin on Mon Oct 21 19:47:24 UTC 2019 , Edited by admin on Mon Oct 21 19:47:24 UTC 2019
PRIMARY
PUBCHEM
1046
Created by admin on Mon Oct 21 19:47:24 UTC 2019 , Edited by admin on Mon Oct 21 19:47:24 UTC 2019
PRIMARY
EVMPD
SUB10163MIG
Created by admin on Mon Oct 21 19:47:24 UTC 2019 , Edited by admin on Mon Oct 21 19:47:24 UTC 2019
PRIMARY
INN
786
Created by admin on Mon Oct 21 19:47:24 UTC 2019 , Edited by admin on Mon Oct 21 19:47:24 UTC 2019
PRIMARY
IUPHAR
7287
Created by admin on Mon Oct 21 19:47:24 UTC 2019 , Edited by admin on Mon Oct 21 19:47:24 UTC 2019
PRIMARY
MESH
D011718
Created by admin on Mon Oct 21 19:47:24 UTC 2019 , Edited by admin on Mon Oct 21 19:47:24 UTC 2019
PRIMARY
LactMed
98-96-4
Created by admin on Mon Oct 21 19:47:24 UTC 2019 , Edited by admin on Mon Oct 21 19:47:24 UTC 2019
PRIMARY
HSDB
98-96-4
Created by admin on Mon Oct 21 19:47:24 UTC 2019 , Edited by admin on Mon Oct 21 19:47:24 UTC 2019
PRIMARY
DRUG BANK
DB00339
Created by admin on Mon Oct 21 19:47:24 UTC 2019 , Edited by admin on Mon Oct 21 19:47:24 UTC 2019
PRIMARY
CAS
98-96-4
Created by admin on Mon Oct 21 19:47:24 UTC 2019 , Edited by admin on Mon Oct 21 19:47:24 UTC 2019
PRIMARY
RXCUI
8987
Created by admin on Mon Oct 21 19:47:24 UTC 2019 , Edited by admin on Mon Oct 21 19:47:24 UTC 2019
PRIMARY RxNorm
MERCK INDEX
M9337
Created by admin on Mon Oct 21 19:47:24 UTC 2019 , Edited by admin on Mon Oct 21 19:47:24 UTC 2019
PRIMARY Merck Index
NCI_THESAURUS
C29395
Created by admin on Mon Oct 21 19:47:24 UTC 2019 , Edited by admin on Mon Oct 21 19:47:24 UTC 2019
PRIMARY