Nalidixic acid

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Nalidixic acid
Nalidixic acid.png
Systematic (IUPAC) name
1-Ethyl-7-methyl-4-oxo-[1,8]naphthyridine-3-carboxylic acid
Clinical data
AHFS/Drugs.com Consumer Drug Information
Pregnancy cat.
Legal status
  • Not FDA approved for clinical use in the United States
Routes Oral
Pharmacokinetic data
Protein binding 90%
Metabolism Partially Hepatic
Half-life 6-7 hours, significantly longer in renal impairment
Identifiers
CAS number 389-08-2 YesY
ATC code J01MB02
PubChem CID 4421
DrugBank DB00779
ChemSpider 4268 YesY
UNII 3B91HWA56M YesY
KEGG D00183 YesY
ChEBI CHEBI:100147 YesY
ChEMBL CHEMBL5 YesY
Chemical data
Formula C12H12N2O3 
Mol. mass 232.235 g/mol
 YesY (what is this?)  (verify)

Nalidixic acid (tradenames Nevigramon, Neggram, Wintomylon and WIN 18,320) is the first of the synthetic quinolone antibiotics.

In the technical sense, it is a naphthyridone, not a quinolone: its ring structure is a 1,8-naphthyridine nucleus that contains two nitrogen atoms, unlike quinoline, which has a single nitrogen atom.[1]

Synthetic quinolone antibiotics were discovered by George Lesher and coworkers as a byproduct of chloroquine manufacture in the 1960s.[1] Used clinically from 1967.[1]

Nalidixic acid is effective primarily against gram-negative bacteria, with minor anti-gram-positive activity. In lower concentrations, it acts in a bacteriostatic manner; that is, it inhibits growth and reproduction. In higher concentrations, it is bactericidal, meaning that it kills bacteria instead of merely inhibiting their growth.

It has historically been used for treating urinary tract infections, caused, for example, by Escherichia coli, Proteus, Shigella, Enterobacter, and Klebsiella. It is no longer clinically used for this indication in the USA as less toxic and more effective agents are available.

It is also a tool in studies as a regulation of bacterial division. It selectively and reversibly blocks DNA replication in susceptible bacteria. Nalidixic acid and related antibiotics inhibit a subunit of DNA gyrase and topoisomerase IV and induce formation of cleavage complexes.[2] It also inhibits the nicking-closing activity on the subunit of DNA gyrase that releases the positive binding stress on the supercoiled DNA.

Adverse effects[edit]

Hives, rash, intense itching, or fainting soon after a dose may be a sign of anaphylaxis. Common adverse effects include rash, itchy skin, blurred or double vision, halos around lights, changes in color vision, nausea, vomiting, and diarrhea. Nalidixic acid may also cause convulsions and hyperglycaemia,[3] photosensitivity reactions,[4] and sometimes haemolytic anaemia,[5][6] thrombocytopenia[7] or leukopenia. Particularly in infants and young children, has been reported occasionally increased intracranial pressure.[8][9][10]

Overdose[edit]

In case of overdose the patient experiences headache, visual disturbances, balance disorders, mental confusion, metabolic acidosis and seizures.[11]

Spectrum of bacterial susceptibility and resistance[edit]

Aeromonas hydrophila, Clostridium and Haemophilus are generally susceptible to nalidixic acid, while other bacteria such as Bifidobacteria, Lactobacillus, Pseudomonas and Staphylococcus are resistant.[12]

Synthesis[edit]

EMME (Ethoxy Methylene Malonic Diethyl Ester)

Naldixic acid synthesis:[13][14] DE 1933463  GB 1338023  BE 612258 

See also[edit]

References[edit]

  1. ^ a b c Emmerson, A. M.; Jones, A. M. (2003). "The Quinolones: Decades of Development and Use" (pdf). The Journal of Antimicrobial Chemotherapy 51 (Suppl 1): 13–20. doi:10.1093/jac/dkg208. PMID 12702699.  edit
  2. ^ Pommier, Y., Leo, E., Zhang, H., Marchand, C. 2010. DNA topoisomerases and their poisoning by anticancer and antibacterial drugs. Chem. Biol. 17: 421-433.
  3. ^ Fraser, A. G.; Harrower, A. D. (December 1977). "Convulsions and Hyperglycaemia Associated with Nalidixic Acid". British Medical Journal 2 (6101): 1518. doi:10.1136/bmj.2.6101.1518. PMC 1632822. PMID 589309. 
  4. ^ Ramsay CA (August 1973). "Photosensitivity from nalidixic acid". Proc. R. Soc. Med. 66 (8): 747. PMC 1645105. PMID 4733958. Retrieved 2014-12-21. 
  5. ^ Gilbertson C, Jones DR (November 1972). "Haemolytic anaemia with nalidixic acid". Br Med J 4 (5838): 493. PMC 1786728. PMID 4653901. Retrieved 2014-12-21. 
  6. ^ Tafani O, Mazzoli M, Landini G, Alterini B (October 1982). "Fatal acute immune haemolytic anaemia caused by nalidixic acid". Br Med J (Clin Res Ed) 285 (6346): 936–7. PMC 1499997. PMID 6811074. Retrieved 2014-12-21. 
  7. ^ Meyboom RH (October 1984). "Thrombocytopenia induced by nalidixic acid". Br Med J (Clin Res Ed) 289 (6450): 962. PMC 1443179. PMID 6435742. Retrieved 2014-12-21. 
  8. ^ Boréus LO, Sundström B (June 1967). "Intracranial hypertension in a child during treatment with nalidixic acid". Br Med J 2 (5554): 744–5. PMC 1841777. PMID 6025983. Retrieved 2014-12-21. 
  9. ^ Kremer L, Walton M, Wardle EN (November 1967). "Nalidixic acid and intracranial hypertension". Br Med J 4 (5577): 488. PMC 1748506. PMID 6055749. Retrieved 2014-12-21. 
  10. ^ Deonna T, Guignard JP (September 1974). "Acute intracranial hypertension after nalidixic acid administration". Arch. Dis. Child. 49 (9): 743. PMC 1649016. PMID 4419059. Retrieved 2014-12-21. 
  11. ^ Eizadi-Mood N (March 2006). "Nalidixic acid overdose and metabolic acidosis". CJEM 8 (2): 78. PMID 17175866. 
  12. ^ "Nalidixic acid spectrum of bacterial susceptibility and Resistance" (pdf). Toku-E. 2011-09-14. Retrieved 2012-05-14. 
  13. ^ Lesher, G. Y.; Froelich, E. J.; Gruett, M. D.; Bailey, J. H.; Brundage, R. P. (1962). "1,8-Naphthyridine Derivatives. A New Class of Chemotherapeutic Agents". Journal of Medicinal and Pharmaceutical Chemistry 5 (5): 1063. doi:10.1021/jm01240a021.  edit
  14. ^ Logemann, W.; Almirante, L.; Caprio, L. (1954). "Studien in der heterocyclischen Reihe. I. Mitteil.: Eine neue Synthese der 2.4-Diamino-6-alkyl-5-aryl-pyrimidine ("Daraprim")". Chemische Berichte 87 (3): 435. doi:10.1002/cber.19540870324.  edit

External links[edit]