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Identification
NameNalidixic Acid
Accession NumberDB00779  (APRD01133)
TypeSmall Molecule
GroupsApproved
DescriptionA synthetic 1,8-naphthyridine antimicrobial agent with a limited bacteriocidal spectrum. It is an inhibitor of the A subunit of bacterial DNA gyrase. [PubChem]
Structure
Thumb
Synonyms
1-Aethyl-7-methyl-1,8-naphthyridin-4-on-3-karbonsaeure
1-Ethyl-1,4-dihydro-7-methyl-4-oxo-1,8-naphthyridine-3-carboxylic acid
1-Ethyl-7-methyl-1,4-dihydro-1,8-naphthyridin-4-one-3-carboxylic acid
1-Ethyl-7-methyl-4-oxo-1,4-dihydro-[1,8]naphthyridine-3-carboxylic acid
1,4-dihydro-1-Ethyl-7-methyl-4-oxo-1,8-naphthyridine-3-carboxylic acid
3-Carboxy-1-ethyl-7-methyl-1,8-naphthyridin-4-one
Acide nalidixique
Acido nalidixico
Acidum Nalidixicum
Nalidixic acid
Nalidixinsäure
External Identifiers
  • Win 18320
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Neggramtablet500 mgoralSanofi Aventis Canada Inc1964-12-312007-03-28Canada
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
AdixNenza Pharma
CuriemylonPanion & BF
DegramDoctor's Chemical Works
DelugiWashington
DixiconJayson
GlanegaMeider
GramazineJohnson
GramonegRanbaxy
Huei YiChen Ho
LisalenbSan Tong
LitalonLi Ta
NadixinPei Jin
NadonCentury
NagominMing Ta
Nal-acidFarmanic Chemipharma
NalicYu Sheng
NalicidTorrent
NalidSquare
NalidinFu Yuan
NalidixDar-Al-Dawa
NaligramAcme
NalitomylonThe Central
NalixAristopharma
NalixidZentiva
NalixinYung Sine
NebactilBeximco
NegachineHor Chen
NevigramonSanofi-Aventis
UnaserusIsei
WintomylonSanofi Aventis
WintorinSankei Yakuhin
YoudixYoshindo
Zuno-NathasidYung Chang
Brand mixturesNot Available
SaltsNot Available
Categories
UNII3B91HWA56M
CAS number389-08-2
WeightAverage: 232.2353
Monoisotopic: 232.08479226
Chemical FormulaC12H12N2O3
InChI KeyInChIKey=MHWLWQUZZRMNGJ-UHFFFAOYSA-N
InChI
InChI=1S/C12H12N2O3/c1-3-14-6-9(12(16)17)10(15)8-5-4-7(2)13-11(8)14/h4-6H,3H2,1-2H3,(H,16,17)
IUPAC Name
1-ethyl-7-methyl-4-oxo-1,4-dihydro-1,8-naphthyridine-3-carboxylic acid
SMILES
CCN1C=C(C(O)=O)C(=O)C2=C1N=C(C)C=C2
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as naphthyridine carboxylic acids and derivatives. These are compounds containing a naphthyridine moiety, where one of the ring atoms bears a carboxylic acid group.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassNaphthyridines
Sub ClassNaphthyridine carboxylic acids and derivatives
Direct ParentNaphthyridine carboxylic acids and derivatives
Alternative Parents
Substituents
  • Naphthyridine carboxylic acid
  • Pyridine carboxylic acid or derivatives
  • Pyridine carboxylic acid
  • Methylpyridine
  • Pyridine
  • Heteroaromatic compound
  • Vinylogous amide
  • Azacycle
  • Monocarboxylic acid or derivatives
  • Carboxylic acid
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Carbonyl group
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Pharmacology
IndicationFor the treatment of urinary tract infections caused by susceptible gram-negative microorganisms, including the majority of E. Coli, Enterobacter species, Klebsiella species, and Proteus species.
PharmacodynamicsNalidixic acid is a quinolone antibacterial agent for oral administration. Nalidixic acid has marked antibacterial activity against gram-negative bacteria including Enterobacter species, Escherichia coli, Morganella Morganii; Proteus Mirabilis, Proteus vulgaris, and Providencia rettgeri. Pseudomonas species are generally resistant to the drug. Nalidixic acid is bactericidal and is effective over the entire urinary pH range. Conventional chromosomal resistance to nalidixic acid taken in full dosage has been reported to emerge in approximately 2 to 14 percent of patients during treatment; however, bacterial resistance to nalidixic acid has not been shown to be transferable via R factor.
Mechanism of actionEvidence exists for Nalidixic acid that its active metabolite, hydroxynalidixic acid, binds strongly, but reversibly, to DNA, interfering with synthesis of RNA and, consequently, with protein synthesis.
Related Articles
AbsorptionFollowing oral administration, nalidixic acid is rapidly absorbed from the gastrointestinal tract. Bioavailability is approximately 96%. Absorption may be delayed if taken with antacids.
Volume of distributionNot Available
Protein bindingNalidixic acid is 93% bound to protein in the blood, and the active metabolite, hydroxynalidixic acid is 63% bound.
Metabolism

Hepatic. 30% of administered dose is metabolized to the active metabolite, hydroxynalidixic acid. Rapid conjugation of parent drug and active metabolite to inactive metabolites. Metabolism may vary widely among individuals. In the urine, hydroxynalidixic acid represents 80 to 85% of the antibacterial activity.

SubstrateEnzymesProduct
Nalidixic Acid
Not Available
Hydroxynalidixic acidDetails
Route of eliminationFollowing oral administration, NegGram is rapidly absorbed from the gastrointestinal tract, partially metabolized in the liver, and rapidly excreted through the kidneys. Approximately four percent of NegGram is excreted in the feces.
Half life1.1 to 2.5 hours in healthy adult patients, and up to 21 hours in patients with impaired renal function.
ClearanceNot Available
ToxicityORAL (LD50): Acute: 1160 mg/kg [Rat]. 572 mg/kg [Mouse]. Toxic psychosis, convulsions, increased intracranial pressure, or metabolic acidosis may occur in patients taking more than the recommended dosage. Vomiting, nausea, and lethargy may also occur following overdosage.
Affected organisms
  • Enteric bacteria and other eubacteria
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.9873
Blood Brain Barrier+0.8945
Caco-2 permeable+0.6315
P-glycoprotein substrateNon-substrate0.5071
P-glycoprotein inhibitor INon-inhibitor0.8838
P-glycoprotein inhibitor IINon-inhibitor0.8566
Renal organic cation transporterNon-inhibitor0.8104
CYP450 2C9 substrateNon-substrate0.7898
CYP450 2D6 substrateNon-substrate0.9116
CYP450 3A4 substrateNon-substrate0.7202
CYP450 1A2 substrateNon-inhibitor0.7888
CYP450 2C9 inhibitorNon-inhibitor0.8934
CYP450 2D6 inhibitorNon-inhibitor0.9115
CYP450 2C19 inhibitorNon-inhibitor0.7834
CYP450 3A4 inhibitorNon-inhibitor0.9531
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8555
Ames testNon AMES toxic0.9133
CarcinogenicityNon-carcinogens0.8815
BiodegradationNot ready biodegradable0.8553
Rat acute toxicity2.0874 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9392
hERG inhibition (predictor II)Non-inhibitor0.8534
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Pharmacoeconomics
Manufacturers
  • Sanofi aventis us llc
  • Mutual pharmaceutical co inc
  • Watson laboratories inc
Packagers
Dosage forms
FormRouteStrength
Tabletoral500 mg
Prices
Unit descriptionCostUnit
Nalidixic acid powder7.2USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point229.5 °CPhysProp
water solubility100 mg/L (at 23 °C)MERCK INDEX (1996)
logP1.59BIOBYTE (1995)
logS-3.37ADME Research, USCD
pKa8.6OSOL,A & HOOVER,JE (1975)
Predicted Properties
PropertyValueSource
Water Solubility2.3 mg/mLALOGPS
logP0.95ALOGPS
logP1.01ChemAxon
logS-2ALOGPS
pKa (Strongest Acidic)5.95ChemAxon
pKa (Strongest Basic)4.68ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count5ChemAxon
Hydrogen Donor Count1ChemAxon
Polar Surface Area70.5 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity62.82 m3·mol-1ChemAxon
Polarizability23.65 Å3ChemAxon
Number of Rings2ChemAxon
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
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, NegativeNot Available
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, NegativeNot Available
References
Synthesis Reference

Charles L. Fox, Jr., Shanta Modak, Keith Reemtsma, “Injection-resistant materials and method of making same through use of nalidixic acid derivatives.” U.S. Patent US4563485, issued July, 1984.

US4563485
General ReferencesNot Available
External Links
ATC CodesJ01MB02
AHFS Codes
  • 08:12.18
PDB EntriesNot Available
FDA labelDownload (47.9 KB)
MSDSDownload (73.2 KB)
Interactions
Drug Interactions
Drug
AcetyldigitoxinAcetyldigitoxin may decrease the cardiotoxic activities of Nalidixic Acid.
BevacizumabBevacizumab may increase the cardiotoxic activities of Nalidixic Acid.
CabazitaxelThe risk or severity of adverse effects can be increased when Cabazitaxel is combined with Nalidixic Acid.
CyclophosphamideCyclophosphamide may increase the cardiotoxic activities of Nalidixic Acid.
DeslanosideDeslanoside may decrease the cardiotoxic activities of Nalidixic Acid.
DigitoxinDigitoxin may decrease the cardiotoxic activities of Nalidixic Acid.
DigoxinDigoxin may decrease the cardiotoxic activities of Nalidixic Acid.
DocetaxelThe risk or severity of adverse effects can be increased when Docetaxel is combined with Nalidixic Acid.
MelphalanThe risk or severity of adverse effects can be increased when Nalidixic Acid is combined with Melphalan.
OuabainOuabain may decrease the cardiotoxic activities of Nalidixic Acid.
PaclitaxelThe risk or severity of adverse effects can be increased when Paclitaxel is combined with Nalidixic Acid.
Picosulfuric acidThe therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Nalidixic Acid.
TrastuzumabTrastuzumab may increase the cardiotoxic activities of Nalidixic Acid.
Food Interactions
  • Take with food to reduce irritation. Drink liberally.

Targets

1. DNA
Kind
Nucleotide
Organism
Human
Pharmacological action
yes
Actions
other
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. 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 ]
  2. Avsaroglu MD, Helmuth R, Junker E, Hertwig S, Schroeter A, Akcelik M, Bozoglu F, Guerra B: Plasmid-mediated quinolone resistance conferred by qnrS1 in Salmonella enterica serovar Virchow isolated from Turkish food of avian origin. J Antimicrob Chemother. 2007 Nov;60(5):1146-50. Epub 2007 Sep 19. [PubMed:17881633 ]
  3. Jain A, Rajeswari MR: Preferential binding of quinolones to DNA with alternating G, C / A, T sequences: a spectroscopic study. J Biomol Struct Dyn. 2002 Oct;20(2):291-9. [PubMed:12354080 ]

Enzymes

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Tryptophan 2,3-dioxygenase activity
Specific Function:
Incorporates oxygen into the indole moiety of tryptophan. Has a broad specificity towards tryptamine and derivatives including D- and L-tryptophan, 5-hydroxytryptophan and serotonin (By similarity).
Gene Name:
TDO2
Uniprot ID:
P48775
Molecular Weight:
47871.215 Da
References
  1. Sanzey B: Modulation of gene expression by drugs affecting deoxyribonucleic acid gyrase. J Bacteriol. 1979 Apr;138(1):40-7. [PubMed:108253 ]

Transporters

Kind
Protein
Organism
Human
Pharmacological action
unknown
Actions
inhibitor
General Function:
Sodium-independent organic anion transmembrane transporter activity
Specific Function:
Involved in the renal elimination of endogenous and exogenous organic anions. Functions as organic anion exchanger when the uptake of one molecule of organic anion is coupled with an efflux of one molecule of endogenous dicarboxylic acid (glutarate, ketoglutarate, etc). Mediates the sodium-independent uptake of 2,3-dimercapto-1-propanesulfonic acid (DMPS) (By similarity). Mediates the sodium-in...
Gene Name:
SLC22A6
Uniprot ID:
Q4U2R8
Molecular Weight:
61815.78 Da
References
  1. Sekine T, Watanabe N, Hosoyamada M, Kanai Y, Endou H: Expression cloning and characterization of a novel multispecific organic anion transporter. J Biol Chem. 1997 Jul 25;272(30):18526-9. [PubMed:9228014 ]
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Drug created on June 13, 2005 07:24 / Updated on August 17, 2016 12:23