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{{drugbox
{{Drugbox
| IUPAC_name = 1-ethyl-7-methyl-4-oxo-[1,8]naphthyridine-3-carboxylic acid
| Watchedfields = changed
| verifiedrevid = 462258277
| IUPAC_name = 1-Ethyl-7-methyl-4-oxo-[1,8]naphthyridine-3-carboxylic acid
| image = Nalidixic acid.png
| image = Nalidixic acid.png
<!--Clinical data-->
| tradename = 
| Drugs.com = {{drugs.com|CDI|nalidixic_acid}}
| pregnancy_category = B <small>[[U.S.]]</small>
| legal_status =  Not FDA approved for clinical use in the United States
| routes_of_administration = Oral
<!--Pharmacokinetic data-->
| bioavailability = 
| protein_bound = 90%
| metabolism = Partially Hepatic
| elimination_half-life = 6-7 hours, significantly longer in [[renal]] impairment
<!--Identifiers-->
| CASNo_Ref = {{cascite|correct|CAS}}
| CAS_number_Ref = {{cascite|correct|??}}
| CAS_number = 389-08-2
| CAS_number = 389-08-2
| ATC_prefix = J01
| ATC_prefix = J01
| ATC_suffix = MB02
| ATC_suffix = MB02
| ATC_supplemental =  
| ATC_supplemental =
| PubChem = 4421
| PubChem = 4421
| DrugBank = APRD01133
| DrugBank_Ref = {{drugbankcite|correct|drugbank}}
| C=12 | H=12 | N=2 | O=3
| DrugBank = DB00779
| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}
| ChemSpiderID = 4268
| UNII_Ref = {{fdacite|correct|FDA}}
| UNII = 3B91HWA56M
| KEGG_Ref = {{keggcite|correct|kegg}}
| KEGG = D00183
| ChEBI_Ref = {{ebicite|correct|EBI}}
| ChEBI = 100147
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 5
 
<!--Chemical data-->
| C=12 | H=12 | N=2 | O=3  
| molecular_weight = 232.235 g/mol
| molecular_weight = 232.235 g/mol
| bioavailability =  
| smiles = O=C\2c1c(nc(cc1)C)N(/C=C/2C(=O)O)CC
| protein_bound = 90%
| StdInChI_Ref = {{stdinchicite|correct|chemspider}}
| metabolism = Partially Hepatic
| StdInChI = 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)
| elimination_half-life = 6-7 hours, significantly longer in [[renal]] impairment
| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}
| pregnancy_category = B <small>[[U.S.]]</small>
| StdInChIKey = MHWLWQUZZRMNGJ-UHFFFAOYSA-N
| legal_status =
| routes_of_administration = Oral
}}
}}
{{SI}}


'''Nalidixic acid''' (tradenames '''Nevigramon''', '''Neggram''', '''Wintomylon''' and '''WIN 18,320''') is the first of the synthetic [[quinolone]] [[antibiotic]]s.


'''Nalidixic acid''' is the basis for [[quinolone]] [[antibiotic]]s.  
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.<ref name=jac2003>{{vcite2 journal | vauthors = Emmerson AM, Jones AM | title = The quinolones: decades of development and use | journal = The Journal of Antimicrobial Chemotherapy | volume = 51 Suppl 1 | issue = Suppl 1 | pages = 13–20 | date = May 2003 | pmid = 12702699 | doi = 10.1093/jac/dkg208 | url = http://jac.oxfordjournals.org/content/51/suppl_1/13.full.pdf | format = pdf }}</ref>


Nalidixic acid is effective against both [[gram-positive]] and [[gram-negative]] [[bacterium|bacteria]]. In lower concentrations, it acts [[bacteriostatic]]ally (that is, it inhibits growth and reproduction). In higher concentrations, it is bactericidal, meaning that it kills bacteria instead of merely inhibiting their growth.
Synthetic quinolone antibiotics were discovered by George Lesher and coworkers as a byproduct of [[chloroquine]] manufacture in the 1960s.<ref name=jac2003 /> Used clinically from 1967.<ref name=jac2003 />


It is especially used in treating [[urinary tract infections]], caused for example by ''[[Escherichia coli]]'', ''[[Proteus (bacterium)|Proteus]]'', ''[[Shigella]]'', ''[[Enterobacter]]'' and ''[[Klebsiella]]''.
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.


== External links ==
It has historically been used for treating [[urinary tract infections]], caused, for example, by ''[[Escherichia coli]]'', ''[[Proteus (bacterium)|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.
* {{MedlinePlusDrugInfo|medmaster|a682042}}
 
* [http://www.healthdigest.org/drugs/nalidixicacid.html HealthDigest.org: Nalidixic acid]
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.<ref>{{cite journal | last1 = Pommier | first1 = Y. | last2 = Leo | first2 = E. | last3 = Zhang | first3 = H. | last4 = Marchand | first4 = C. | year = 2010 | title = DNA topoisomerases and their poisoning by anticancer and antibacterial drugs | url = | journal = Chem. Biol | volume = 17 | issue = | pages = 421–433 | doi=10.1016/j.chembiol.2010.04.012 | pmid=20534341}}</ref> 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 ==
 
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 [[convulsion]]s and [[hyperglycaemia]],<ref>{{vcite2 journal | vauthors = Fraser AG, Harrower AD | title = Convulsions and hyperglycaemia associated with nalidixic acid | journal = British Medical Journal | volume = 2 | issue = 6101 | pages = 1518 | date = Dec 1977 | pmid = 589309 | pmc = 1632822 | doi = 10.1136/bmj.2.6101.1518 }}</ref> photosensitivity reactions,<ref name="pmid4733958">{{vcite2 journal | vauthors = Ramsay CA | title = Photosensitivity from nalidixic acid | journal = Proceedings of the Royal Society of Medicine | volume = 66 | issue = 8 | pages = 747 | date = Aug 1973 | pmid = 4733958 | pmc = 1645105 | doi =  }}</ref> and sometimes haemolytic anaemia,<ref name="pmid4653901">{{vcite2 journal | vauthors = Gilbertson C, Jones DR | title = Haemolytic anaemia with nalidixic acid | journal = British Medical Journal | volume = 4 | issue = 5838 | pages = 493 | date = Nov 1972 | pmid = 4653901 | pmc = 1786728 | doi =  10.1136/bmj.4.5838.493-a}}</ref><ref name="pmid6811074">{{vcite2 journal | vauthors = Tafani O, Mazzoli M, Landini G, Alterini B | title = Fatal acute immune haemolytic anaemia caused by nalidixic acid | journal = British Medical Journal | volume = 285 | issue = 6346 | pages = 936–7 | date = Oct 1982 | pmid = 6811074 | pmc = 1499997 | doi =  10.1136/bmj.285.6346.936-a}}</ref> thrombocytopenia<ref name="pmid6435742">{{vcite2 journal | vauthors = Meyboom RH | title = Thrombocytopenia induced by nalidixic acid | journal = British Medical Journal | volume = 289 | issue = 6450 | pages = 962 | date = Oct 1984 | pmid = 6435742 | pmc = 1443179 | doi =  10.1136/bmj.289.6450.962}}</ref> or leukopenia. Particularly in [[infants]] and young children, has been reported occasionally increased [[intracranial pressure]].<ref name="pmid6025983">{{vcite2 journal | vauthors = Boréus LO, Sundström B | title = Intracranial hypertension in a child during treatment with nalidixic acid | journal = British Medical Journal | volume = 2 | issue = 5554 | pages = 744–5 | date = Jun 1967 | pmid = 6025983 | pmc = 1841777 | doi =  10.1136/bmj.2.5554.744}}</ref><ref name="pmid6055749">{{vcite2 journal | vauthors = Kremer L, Walton M, Wardle EN | title = Nalidixic acid and intracranial hypertension | journal = British Medical Journal | volume = 4 | issue = 5577 | pages = 488 | date = Nov 1967 | pmid = 6055749 | pmc = 1748506 | doi =  10.1136/bmj.4.5577.488-a}}</ref><ref name="pmid4419059">{{vcite2 journal | vauthors = Deonna T, Guignard JP | title = Acute intracranial hypertension after nalidixic acid administration | journal = Archives of Disease in Childhood | volume = 49 | issue = 9 | pages = 743 | date = Sep 1974 | pmid = 4419059 | pmc = 1649016 | doi =  10.1136/adc.49.9.743}}</ref>
 
== Overdose ==
 
In case of overdose the patient experiences [[headache]], visual disturbances, balance disorders, [[mental confusion]], metabolic acidosis and [[seizures]].<ref name="pmid17175866">{{vcite2 journal | vauthors = Eizadi-Mood N | title = Nalidixic acid overdose and metabolic acidosis | journal = Cjem | volume = 8 | issue = 2 | pages = 78 | date = Mar 2006 | pmid = 17175866 | doi =  }}</ref>
 
== Spectrum of bacterial susceptibility and resistance ==
 
''[[Aeromonas hydrophila]]'', ''[[Clostridium]]'' and ''[[Haemophilus]]'' are generally susceptible to nalidixic acid, while other bacteria such as ''[[Bifidobacteria]]'', ''[[Lactobacillus]]'', ''[[Pseudomonas]]'' and ''[[Staphylococcus]]'' are resistant.<ref>{{ cite web | title = Nalidixic acid spectrum of bacterial susceptibility and Resistance | url = http://www.toku-e.com/Upload/Products/PDS/20120522005430.pdf | format = pdf | publisher = Toku-E | date = 2011-09-14 | accessdate = 2012-05-14 }}</ref>


== See also ==
== Synthesis ==
* [[DNA gyrase]]


{{QuinoloneAntiBiotics}}
EMME ([[Ethoxy Methylene Malonic Diethyl Ester]])
[[File:Naldixic acid synthesis.png|thumb|center|700px|Naldixic acid synthesis:<ref>{{vcite2 journal | vauthors = Lesher GY, Froelich EJ, Gruett MD, Bailey JH, Brundage RP | title = 1,8-Naphthyridine derivatives. A new class of chemotherapeutic agents | journal = Journal of Medicinal and Pharmaceutical Chemistry | volume = 91 | date = Sep 1962 | pmid = 14056431 | doi = 10.1021/jm01240a021 }}</ref><ref>{{vcite2 journal | vauthors =Logemann W, Almirante L, Caprio L|title=Studien in der heterocyclischen Reihe. I. Mitteil.: Eine neue Synthese der 2.4-Diamino-6-alkyl-5-aryl-pyrimidine ("Daraprim") | journal = Chemische Berichte | date = Mar 1954 | volume = 87 | issue = 3 | pages = 435–439 | doi=10.1002/cber.19540870324}} {{Cite patent|DE|1933463}} {{Cite patent|GB|1338023}} {{Cite patent|BE|612258}}</ref> ]]


[[Category:Quinolone antibiotics]]
== See also ==
*[[Amfonelic acid]]
*[[Oxolinic acid]]


== References ==
{{reflist|33em}}


== External links ==
* {{MedlinePlusDrugInfo|medmaster|a682042}}{{dead link|date=June 2012}}
* {{ cite web | url = http://www.healthdigest.org/topics/category/1464-nalidixic-acid-dosage-interactions-side-effects-how-to-use | publisher = HealthDigest.org | title = Nalidixic acid }}


[[de:Nalidixinsäure]]
{{QuinoloneAntiBiotics}}
[[fr:Acide nalidixique]]
[[it:Acido nalidixico]]
[[pl:Kwas nalidyksowy]]
[[th:กรดนาลิดิซิก]]


{{WH}}
[[Category:Quinolone antibiotics]]
{{WikiDoc Sources}}
[[Category:Naphthyridines]]
[[Category:WIN compounds]]

Revision as of 19:32, 7 April 2015

Nalidixic acid
Clinical data
AHFS/Drugs.comConsumer Drug Information
Pregnancy
category
Routes of
administration		Oral
ATC code
Legal status
Legal status
  • Not FDA approved for clinical use in the United States
Pharmacokinetic data
Protein binding90%
MetabolismPartially Hepatic
Elimination half-life6-7 hours, significantly longer in renal impairment
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
E number{{#property:P628}}
ECHA InfoCard{{#property:P2566}}Lua error in Module:EditAtWikidata at line 36: attempt to index field 'wikibase' (a nil value).
Chemical and physical data
FormulaC12H12N2O3
Molar mass232.235 g/mol
3D model (JSmol)
  (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

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

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

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

EMME (Ethoxy Methylene Malonic Diethyl Ester)

File:Naldixic acid synthesis.png
Naldixic acid synthesis:[13][14]

See also

References

  1. ↑ 1.0 1.1 1.2 Emmerson AM, Jones AM (May 2003). "The quinolones: decades of development and use" (pdf). The Journal of Antimicrobial Chemotherapy. 51 Suppl 1 (Suppl 1): 13–20. doi:10.1093/jac/dkg208. PMID 12702699.
  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. doi:10.1016/j.chembiol.2010.04.012. PMID 20534341.
  3. ↑ Fraser AG, Harrower AD (Dec 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 (Aug 1973). "Photosensitivity from nalidixic acid". Proceedings of the Royal Society of Medicine. 66 (8): 747. PMC 1645105. PMID 4733958.
  5. ↑ Gilbertson C, Jones DR (Nov 1972). "Haemolytic anaemia with nalidixic acid". British Medical Journal. 4 (5838): 493. doi:10.1136/bmj.4.5838.493-a. PMC 1786728. PMID 4653901.
  6. ↑ Tafani O, Mazzoli M, Landini G, Alterini B (Oct 1982). "Fatal acute immune haemolytic anaemia caused by nalidixic acid". British Medical Journal. 285 (6346): 936–7. doi:10.1136/bmj.285.6346.936-a. PMC 1499997. PMID 6811074.
  7. ↑ Meyboom RH (Oct 1984). "Thrombocytopenia induced by nalidixic acid". British Medical Journal. 289 (6450): 962. doi:10.1136/bmj.289.6450.962. PMC 1443179. PMID 6435742.
  8. ↑ Boréus LO, Sundström B (Jun 1967). "Intracranial hypertension in a child during treatment with nalidixic acid". British Medical Journal. 2 (5554): 744–5. doi:10.1136/bmj.2.5554.744. PMC 1841777. PMID 6025983.
  9. ↑ Kremer L, Walton M, Wardle EN (Nov 1967). "Nalidixic acid and intracranial hypertension". British Medical Journal. 4 (5577): 488. doi:10.1136/bmj.4.5577.488-a. PMC 1748506. PMID 6055749.
  10. ↑ Deonna T, Guignard JP (Sep 1974). "Acute intracranial hypertension after nalidixic acid administration". Archives of Disease in Childhood. 49 (9): 743. doi:10.1136/adc.49.9.743. PMC 1649016. PMID 4419059.
  11. ↑ Eizadi-Mood N (Mar 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 GY, Froelich EJ, Gruett MD, Bailey JH, Brundage RP (Sep 1962). "1,8-Naphthyridine derivatives. A new class of chemotherapeutic agents". Journal of Medicinal and Pharmaceutical Chemistry. 91. doi:10.1021/jm01240a021. PMID 14056431.
  14. ↑ Logemann W, Almirante L, Caprio L (Mar 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): 435–439. doi:10.1002/cber.19540870324. DE 1933463  GB 1338023  BE 612258 

External links

Template:QuinoloneAntiBiotics

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