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Identification
Name Aminosalicylic Acid
Accession Number DB00233 (APRD00749, EXPT00693)
Type small molecule
Groups approved
Description

An antitubercular agent often administered in association with isoniazid. The sodium salt of the drug is better tolerated than the free acid. [PubChem]
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms
4-aminosalicylic acid
4-ASA
Amino-PAS
Aminosalicylate Sodium
APAS
P-Aminosalicylic Acid
Para-Amino Salicylic Acid
Para-aminosalicylic acid
PAS
PASK
Salts Not Available
Brand names
Name Company
Aminopar
Aminox
Apacil
Deapasil
Entepas
Ferrosan
Gabbropas
Hellipidyl
Kyselina P-Aminosalicylova
Neopasalate
Osacyl
Pamacyl
Pamisyl
Para-Pas
Paramycin
Parasal
Parasalicil
Parasalindon
PAS-C
Pasa
Pasalon
Pasara
Pascorbic
Pasdium
Pasem
Paser
Pasmed
Pasnodia
Pasolac
Propasa
Rezipas
Sanipirol-4
Sanipriol-4
First Prev Next Last
Brand mixtures Not Available
Categories
  • Antituberculosis Agents
  • Antitubercular Agents
CAS number 65-49-6
Weight Average: 153.1354
Monoisotopic: 153.042593095
Chemical Formula C7H7NO3
InChI Key InChIKey=WUBBRNOQWQTFEX-UHFFFAOYSA-N
InChI
InChI=1S/C7H7NO3/c8-4-1-2-5(7(10)11)6(9)3-4/h1-3,9H,8H2,(H,10,11)
Plain Text
IUPAC Name
4-amino-2-hydroxybenzoic acid
SMILES
NC1=CC(O)=C(C=C1)C(O)=O
Plain Text
Mass Spec show (9.18 KB)
Taxonomy
Kingdom Organic
Classes
  • Salicylates and Derivatives
  • Aminobenzoates
  • Aminophenols and Derivatives
Substructures
  • Hydroxy Compounds
  • Benzyl Alcohols and Derivatives
  • Acetates
  • Benzoates
  • Salicylates and Derivatives
  • Phenols and Derivatives
  • Aliphatic and Aryl Amines
  • Benzene and Derivatives
  • Aminobenzoates
  • Aminophenols and Derivatives
  • Carboxylic Acids and Derivatives
  • Aromatic compounds
  • Benzoyl Derivatives
  • Phenyl Esters
  • Anilines
Pharmacology
Indication For the treatment of tuberculosis
Pharmacodynamics Aminosalicylic acid is an anti-mycobacterial agent used with other anti-tuberculosis drugs (most often isoniazid) for the treatment of all forms of active tuberculosis due to susceptible strains of tubercle bacilli. The two major considerations in the clinical pharmacology of aminosalicylic acid are the prompt production of a toxic inactive metabolite under acid conditions and the short serum half life of one hour for the free drug. Aminosalicylic acid is bacteriostatic against Mycobacterium tuberculosis (prevents the multiplying of bacteria without destroying them). It also inhibits the onset of bacterial resistance to streptomycin and isoniazid.
Mechanism of action There are two mechanisms responsible for aminosalicylic acid's bacteriostatic action against Mycobacterium tuberculosis. Firstly, aminosalicylic acid inhibits folic acid synthesis (without potentiation with antifolic compounds). The binding of para-aminobenzoic acid to pteridine synthetase acts as the first step in folic acid synthesis. Aminosalicylic acid binds pteridine synthetase with greater affinity than para-aminobenzoic acid, effectively inhibiting the synthesis of folic acid. As bacteria are unable to use external sources of folic acid, cell growth and multiplication slows. Secondly, aminosalicylic acid may inhibit the synthesis of the cell wall component, mycobactin, thus reducing iron uptake by M. tuberculosis.
Absorption Not Available
Volume of distribution Not Available
Protein binding 50-60%
Metabolism Hepatic.
Route of elimination Not Available
Half life Not Available
Clearance Not Available
Toxicity LD50=4 gm/kg (orally in mice); LD50=3650 mg/kg (orally in rabbits)
Affected organisms
  • Mycobacteria
Pathways Not Available
Pharmacoeconomics
Manufacturers
  • Century pharmaceuticals inc
  • Hexcel chemical products
  • Panray corp sub ormont drug and chemical co inc
  • Lannett co inc
  • Consolidated midland corp
  • Jacobus pharmaceutical co
  • Bristol myers squibb co
Packagers
Dosage forms
Form Route Strength
Granule Oral
Prices
Unit description Cost Unit
Paser granules 4 gm packet 3.59 USD packet
Aminosalicylic acid powder 2.4 USD g
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents Not Available
Properties
State solid
Experimental Properties
Property Value Source
melting point 150.5 dec °C PhysProp
water solubility 1690 mg/L (at 23 °C) YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP 0.89 SANGSTER (1994)
pKa 2.05 (at 25 °C) KORTUM,G ET AL (1961)
Predicted Properties
Property Value Source
water solubility 1.18e+01 g/l ALOGPS
logP 0.62 ALOGPS
logP 0.83 ChemAxon
logS -1.1 ALOGPS
pKa (strongest acidic) 3.68 ChemAxon
pKa (strongest basic) 2.19 ChemAxon
physiological charge -1 ChemAxon
hydrogen acceptor count 4 ChemAxon
hydrogen donor count 3 ChemAxon
polar surface area 83.55 ChemAxon
rotatable bond count 1 ChemAxon
refractivity 40 ChemAxon
polarizability 14.29 ChemAxon
References
Synthesis Reference Not Available
General Reference Not Available
External Links
Resource Link
KEGG Drug D00162 Link_out
KEGG Compound C02518 Link_out
PubChem Compound 4649 Link_out
PubChem Substance 46505572 Link_out
ChemSpider 4488 Link_out
ChEBI 27565 Link_out
ChEMBL 27565 Link_out
PharmGKB PA448382 Link_out
HET BHA Link_out
RxList http://www.rxlist.com/cgi/generic2/paser.htm Link_out
Drugs.com http://www.drugs.com/cdi/aminosalicylic-acid-controlled-release-granules-packet.html Link_out
Wikipedia http://en.wikipedia.org/wiki/Aminosalicylic_acid Link_out
ATC Codes
  • J04AA01
AHFS Codes Not Available
PDB Entries
FDA label Not Available
MSDS show (73.6 KB)
Interactions
Drug Interactions
Drug Interaction
Azathioprine Aminosalicylic acid may increase the toxicity of thiopurine, azathioprine.
Mercaptopurine Aminosalicylic acid may increase the toxicity of thiopurine, mercaptopurine.
Sulindac Risk of additive toxicity (e.g. bleed risk). Aminosalicylic acid may decrease the serum concentration of sulindac. Consider alternate therapy or monitor for changes in the therapeutic effects of sulindac and adverse effects of both agents if the interacting agent is initiated, discontinued or dose changed.
Thioguanine Aminosalicylic acid may increase the toxicity of thiopurine, thioguanine.
Tiaprofenic acid Increased risk of gastrointestinal bleeding.
Tolmetin Additive effects increase the risk of GI bleeding. Monitor for increased bleeding risk during concomitant therapy.
Trandolapril The salicylate, Aminosalicylic acid, may reduce the efficacy of Trandolapril. Monitor for changes in Trandolapril efficacy if Aminosalicylic acid is initiated, discontinued or dose changed.
Treprostinil The prostacyclin analogue, Treprostinil, may increase the risk of bleeding when combined with the salicylate, Aminosalicylic acid. Monitor for increased bleeding during concomitant thearpy.
Warfarin The antiplatelet effects of aminosalicylic acid may increase the bleed risk associated with warfarin.
Food Interactions
  • Take without regard to meals.
Targets

1. Prostaglandin G/H synthase 2

Pharmacological action: unknown
Actions: inhibitor

May have a role as a major mediator of inflammation and/or a role for prostanoid signaling in activity-dependent plasticity

Organism class: human
UniProt ID: P35354 Link_out
Gene: PTGS2 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Mifflin RC, Saada JI, Di Mari JF, Valentich JD, Adegboyega PA, Powell DW: Aspirin-mediated COX-2 transcript stabilization via sustained p38 activation in human intestinal myofibroblasts. Mol Pharmacol. 2004 Feb;65(2):470-8. Pubmed
  2. Generini S, Fiori G, Matucci Cerinic M: Therapy of spondylarthropathy in inflammatory bowel disease. Clin Exp Rheumatol. 2002 Nov-Dec;20(6 Suppl 28):S88-94. Pubmed
  3. Distrutti E, Sediari L, Mencarelli A, Renga B, Orlandi S, Russo G, Caliendo G, Santagada V, Cirino G, Wallace JL, Fiorucci S: 5-Amino-2-hydroxybenzoic acid 4-(5-thioxo-5H-[1,2]dithiol-3yl)-phenyl ester (ATB-429), a hydrogen sulfide-releasing derivative of mesalamine, exerts antinociceptive effects in a model of postinflammatory hypersensitivity. J Pharmacol Exp Ther. 2006 Oct;319(1):447-58. Epub 2006 Jul 19. Pubmed
  4. Cipolla G, Crema F, Sacco S, Moro E, de Ponti F, Frigo G: Nonsteroidal anti-inflammatory drugs and inflammatory bowel disease: current perspectives. Pharmacol Res. 2002 Jul;46(1):1-6. Pubmed
  5. Pruzanski W, Stefanski E, Vadas P, Ramamurthy NS: Inhibition of extracellular release of proinflammatory secretory phospholipase A2 (sPLA2) by sulfasalazine: a novel mechanism of anti-inflammatory activity. Biochem Pharmacol. 1997 Jun 15;53(12):1901-7. Pubmed

2. Inhibitor of nuclear factor kappa-B kinase subunit alpha

Pharmacological action: unknown
Actions: inhibitor
UniProt ID: O15111 Link_out
Gene: CHUK
SNPs: SNPJam Report Link_out

References:
  1. Bantel H, Berg C, Vieth M, Stolte M, Kruis W, Schulze-Osthoff K: Mesalazine inhibits activation of transcription factor NF-kappaB in inflamed mucosa of patients with ulcerative colitis. Am J Gastroenterol. 2000 Dec;95(12):3452-7. Pubmed
  2. Allgayer H: Review article: mechanisms of action of mesalazine in preventing colorectal carcinoma in inflammatory bowel disease. Aliment Pharmacol Ther. 2003 Sep;18 Suppl 2:10-4. Pubmed
  3. Weber CK, Liptay S, Wirth T, Adler G, Schmid RM: Suppression of NF-kappaB activity by sulfasalazine is mediated by direct inhibition of IkappaB kinases alpha and beta. Gastroenterology. 2000 Nov;119(5):1209-18. Pubmed

3. Arachidonate 5-lipoxygenase

Pharmacological action: unknown
Actions: inhibitor
Organism class: human
UniProt ID: P09917 Link_out
Gene: ALOX5 Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Nielsen OH, Bukhave K, Elmgreen J, Ahnfelt-Ronne I: Inhibition of 5-lipoxygenase pathway of arachidonic acid metabolism in human neutrophils by sulfasalazine and 5-aminosalicylic acid. Dig Dis Sci. 1987 Jun;32(6):577-82. Pubmed
  2. Allgayer H, Eisenburg J, Paumgartner G: Soybean lipoxygenase inhibition: studies with the sulphasalazine metabolites N-acetylaminosalicylic acid, 5-aminosalicylic acid and sulphapyridine. Eur J Clin Pharmacol. 1984;26(4):449-51. Pubmed
  3. Sircar JC, Schwender CF, Carethers ME: Inhibition of soybean lipoxygenase by sulfasalazine and 5-aminosalicylic acid: a possible mode of action in ulcerative colitis. Biochem Pharmacol. 1983 Jan 1;32(1):170-2. Pubmed

4. Group IIE secretory phospholipase A2

Pharmacological action: unknown
Actions: unknown

PA2 catalyzes the calcium-dependent hydrolysis of the 2- acyl groups in 3-sn-phosphoglycerides. Has a preference for arachidonic-containing phospholipids

Organism class: human
UniProt ID: Q9NZK7 Link_out
Gene: PLA2G2E Link_out
Protein Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE: The Protein Data Bank. Nucleic Acids Res. 2000 Jan 1;28(1):235-42. Pubmed

5. 2-amino-4-hydroxy-6-hydroxymethyldihydropteridine pyrophosphokinase

Pharmacological action: unknown
Actions: unknown
Organism class: bacterial
UniProt ID: P64143 Link_out
Gene: folK
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. Overington JP, Al-Lazikani B, Hopkins AL: How many drug targets are there? Nat Rev Drug Discov. 2006 Dec;5(12):993-6. Pubmed
  2. 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
Enzymes

1. Myeloperoxidase

Actions: inhibitor

Part of the host defense system of polymorphonuclear leukocytes. It is responsible for microbicidal activity against a wide range of organisms. In the stimulated PMN, MPO catalyzes the production of hypohalous acids, primarily hypochlorous acid in physiologic situations, and other toxic intermediates that greatly enhance PMN microbicidal activity

UniProt ID: P05164 Link_out
Gene: MPO Link_out
Protein Sequence: FASTA
Gene Sequence: FASTA
SNPs: SNPJam Report Link_out

References:
  1. von Ritter C, Grisham MB, Granger DN: Sulfasalazine metabolites and dapsone attenuate formyl-methionyl-leucyl-phenylalanine-induced mucosal injury in rat ileum. Gastroenterology. 1989 Mar;96(3):811-6. Pubmed
  2. Gorgulu S, Yagci G, Kaymakcioglu N, Ozkara M, Kurt B, Ozcan A, Kaya O, Sadir S, Tufan T: Hyperbaric oxygen enhances the efficiency of 5-aminosalicylic acid in acetic acid-induced colitis in rats. Dig Dis Sci. 2006 Mar;51(3):480-7. Pubmed]
Comments
Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19