Banner
targets (1) enzymes (2)
for drugs
Identification
Name Linezolid
Accession Number DB00601 (APRD01073, DB08769)
Type small molecule
Groups approved
Description

Linezolid is a synthetic antibiotic, the first of the oxazolidinone class, used for the treatment of infections caused by multi-resistant bacteria including streptococcus and methicillin-resistant Staphylococcus aureus (MRSA). The drug works by inhibiting the initiation of bacterial protein synthesis.
Structure Thumb
Download: MOL | SDF | SMILES | InChI
Display: 2D Structure | 3D Structure
Synonyms Not Available
Salts Not Available
Brand names
Name Company
Linezlid
Zyvox
Zyvoxid
Brand mixtures Not Available
Categories
  • Anti-Infective Agents
  • Protein Synthesis Inhibitors
  • Antibacterial Agents
CAS number 165800-03-3
Weight Average: 337.3461
Monoisotopic: 337.143784348
Chemical Formula C16H20FN3O4
InChI Key InChIKey=TYZROVQLWOKYKF-ZDUSSCGKSA-N
InChI
InChI=1S/C16H20FN3O4/c1-11(21)18-9-13-10-20(16(22)24-13)12-2-3-15(14(17)8-12)19-4-6-23-7-5-19/h2-3,8,13H,4-7,9-10H2,1H3,(H,18,21)/t13-/m0/s1
Plain Text
IUPAC Name
N-{[(5S)-3-[3-fluoro-4-(morpholin-4-yl)phenyl]-2-oxo-1,3-oxazolidin-5-yl]methyl}acetamide
SMILES
CC(=O)NC[C@H]1CN(C(=O)O1)C1=CC(F)=C(C=C1)N1CCOCC1
Plain Text
Mass Spec Not Available
Taxonomy
Kingdom Organic
Classes
  • Carbamates and Derivatives
  • Benzene and Derivatives
  • Halobenzenes
  • Morpholines
  • Oxazolidinones
  • Anilines
Substructures
  • Carbamates and Derivatives
  • Amino Ketones
  • Aliphatic and Aryl Amines
  • Ethers
  • Benzene and Derivatives
  • Carboxylic Acids and Derivatives
  • Halobenzenes
  • Heterocyclic compounds
  • Aromatic compounds
  • Carboxamides and Derivatives
  • Morpholines
  • Oxazolidinones
  • Aryl Halides
  • Anilines
Pharmacology
Indication For the treatment of bacterial infections caused by susceptible strains of vancomycin resistant Enterococcus faecium, Staphylococcal aureus (methicillin resistant and susceptible strains), Streptococcus pneumoniae, Streptococcus pyogenes, Streptococcus agalactiae.
Pharmacodynamics Linezolid is a synthetic antibacterial agent of a new class of antibiotics, the oxazolidinones, which has clinical utility in the treatment of infections caused by aerobic Gram-positive bacteria. The in vitro spectrum of activity of linezolid also includes certain Gram-negative bacteria and anaerobic bacteria. Susceptible organisms include methicillin- and vancomycin-resistant staphylococci, vancomycin-resistant enterococci, penicillin-resistant pneumococci and anaerobes. Oxazolidinones inhibit protein synthesis by binding at the P site at the ribosomal 50S subunit. Resistance to other protein synthesis inhibitors does not affect oxazolidinone activity, however rare development of oxazolidinone resistance cases, associated with 23S rRNA alterations during treatment have been reported. Linezolid inhibits bacterial protein synthesis through a mechanism of action different from that of other antibacterial agents; therefore, cross-resistance between linezolid and other classes of antibiotics is unlikely.
Mechanism of action Linezolid is a synthetic antibacterial agent of the oxazolidinone class of antibiotics. It has in vitro activity against aerobic Gram positive bacteria, certain Gram negative bacteria and anaerobic microorganisms. It selectively inhibits bacterial protein synthesis through binding to sites on the bacterial ribosome and prevents the formation of a functional 70S-initiation complex. Specifically, linezolid binds to a site on the bacterial 23S ribosomal RNA of the 50S subunit and prevents the formation of a functional 70S initiation complex, which is an essential component of the bacterial translation process. The results of time-kill studies have shown linezolid to be bacteriostatic against enterococci and staphylococci. For streptococci, linezolid was found to be bactericidal for the majority of strains. Linezolid is also a reversible, nonselective inhibitor of monoamine oxidase. Therefore, linezolid has the potential for interaction with adrenergic and serotonergic agents.
Absorption Linezolid is rapidly and extensively absorbed after oral dosing. Maximum plasma concentrations are reached approximately 1 to 2 hours after dosing, and the absolute bioavailability is approximately 100%.
Volume of distribution
  • 40 to 50 L [healthy adult volunteers]
Protein binding 31%
Metabolism
Linezolid is primarily metabolized by oxidation of the morpholine ring, which results in two inactive ring-opened carboxylic acid metabolites: the aminoethoxyacetic acid metabolite (A), and the hydroxyethyl glycine metabolite

Important The metabolism module of DrugBank is currently in beta. Questions or suggestions? Please contact us.

Substrate Enzymes Product
Linezolid
    		aminoethoxyacetic acid Details
    Linezolid
      		Hydroxyethyl glycine Details
      Route of elimination Not Available
      Half life 4.5-5.5 hours
      Clearance Not Available
      Toxicity Clinical signs of acute toxicity lead to decreased activity, ataxia, vomiting and tremors.
      Affected organisms
      • Gram negative and gram positive bacteria
      Pathways Not Available
      Pharmacoeconomics
      Manufacturers
      • Pharmacia and upjohn co
      Packagers
      Dosage forms
      Form Route Strength
      Solution Intravenous
      Tablet Oral
      Prices
      Unit description Cost Unit
      Zyvox 600 mg tablet 93.81 USD tablet
      Zyvox 200 mg/100 ml iv soln 0.6 USD ml
      DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
      Patents
      Country Patent Number Approved Expires (estimated)
      United States 6514529 2001-09-15 2021-09-15
      United States 5688792 1994-11-18 2014-11-18
      Canada 2168560 2001-08-14 2014-08-16
      Properties
      State solid
      Experimental Properties
      Property Value Source
      water solubility 3 mg/mL Not Available
      logP 0.9 Not Available
      Predicted Properties
      Property Value Source
      water solubility 1.44e+00 g/l ALOGPS
      logP 0.61 ALOGPS
      logP 0.64 ChemAxon
      logS -2.4 ALOGPS
      pKa (strongest acidic) 14.45 ChemAxon
      pKa (strongest basic) -0.66 ChemAxon
      physiological charge 0 ChemAxon
      hydrogen acceptor count 5 ChemAxon
      hydrogen donor count 1 ChemAxon
      polar surface area 71.11 ChemAxon
      rotatable bond count 4 ChemAxon
      refractivity 84.47 ChemAxon
      polarizability 34.06 ChemAxon
      References
      Synthesis Reference Not Available
      General Reference
      1. Link
      2. Park IN, Hong SB, Oh YM, Kim MN, Lim CM, Lee SD, Koh Y, Kim WS, Kim DS, Kim WD, Shim TS: Efficacy and tolerability of daily-half dose linezolid in patients with intractable multidrug-resistant tuberculosis. J Antimicrob Chemother. 2006 Sep;58(3):701-4. Epub 2006 Jul 19. Pubmed
      External Links
      Resource Link
      KEGG Drug D00947 Link_out
      KEGG Compound C08146 Link_out
      PubChem Compound 441401 Link_out
      PubChem Substance 46504452 Link_out
      ChemSpider 390139 Link_out
      BindingDB 50116067 Link_out
      Therapeutic Targets Database DAP000398 Link_out
      PharmGKB PA450233 Link_out
      HET ZLD Link_out
      Drug Product Database 2243684 Link_out
      RxList http://www.rxlist.com/cgi/generic3/linezolid.htm Link_out
      Drugs.com http://www.drugs.com/cdi/linezolid.html Link_out
      PDRhealth http://www.pdrhealth.com/drug_info/rxdrugprofiles/drugs/zyv1556.shtml Link_out
      Wikipedia http://en.wikipedia.org/wiki/Linezolid Link_out
      ATC Codes
      • J01XX08
      AHFS Codes
      • 08:12.28.24
      PDB Entries Not Available
      FDA label show (106 KB)
      MSDS show (43.7 KB)
      Interactions
      Drug Interactions
      Drug Interaction
      Bezafibrate MAO Inhibitors may enhance the adverse/toxic effect of Bezafibrate. Avoid concomitant use of bezafibrate with monoamine oxidase inhibitors (MAOIs) like linezolid.
      Brimonidine MAO Inhibitors like linezolid may enhance the hypertensive effect of Alpha2-Agonists (Ophthalmic). The concomitant use of monoamine oxidase inhibitors and ophthalmic alpha2 agonists is contraindicated.
      Buprenorphine Buprenorphine may enhance the adverse/toxic effect of MAO Inhibitors like linezolid. When possible, avoid use of buprenorphine in patients who have used a monoamine oxidase inhibitor within the past 14 days due to possible severe adverse effects.
      Citalopram Combination associated with possible serotoninergic syndrome
      Desvenlafaxine Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.
      Dobutamine Possible increase of arterial pressure
      Dopamine Possible increase of arterial pressure
      Ephedra Possible increase of arterial pressure
      Ephedrine Possible increase of arterial pressure
      Epinephrine Possible increase of arterial pressure
      Escitalopram Combination associated with possible serotoninergic syndrome
      Fenoterol Possible increase of arterial pressure
      Fluoxetine Linezolide, a MAO inhibitor, may increase the serotonergic effect of fluoxetine, a SSRI. Increased for of serotonin syndrome. Concomitant therapy should be avoided.
      Fluvoxamine Combination associated with possible serotoninergic syndrome
      Isoproterenol Possible increase of arterial pressure
      Mephentermine Possible increase of arterial pressure
      Metaraminol Possible increase of arterial pressure
      Methoxamine Possible increase of arterial pressure
      Nefazodone Combination associated with possible serotoninergic syndrome
      Norepinephrine Possible increase of arterial pressure
      Orciprenaline Possible increase of arterial pressure
      Paroxetine Combination associated with possible serotoninergic syndrome
      Phenylephrine Possible increase of arterial pressure
      Phenylpropanolamine Possible increase of arterial pressure
      Pirbuterol Possible increase of arterial pressure
      Procaterol Possible increase of arterial pressure
      Pseudoephedrine Possible increase of arterial pressure
      Salbutamol Possible increase of arterial pressure
      Sertraline Combination associated with possible serotoninergic syndrome
      Terbutaline Possible increase of arterial pressure
      Tetrabenazine Tetrabenazine may increase the adverse/toxic effects of Linezolid. Concomitant therapy is contraindicated.
      Tolcapone Tolcapone and Linezolid decrease the metabolism of endogenous catecholamines. Concomitant therapy may result in increased catecholamine effects. Consider alternate therapy or use cautiously and monitor for increased catecholamine effects.
      Tramadol Tramadol increases the risk of serotonin syndrome and seizure induction by the MAO inhibitor, Linezolid.
      Tranylcypromine The MAO inhibitor, Tranylcypromine, may increase the adverse effects of Linezolid. These agents should not be administered within 14 days of each other.
      Trazodone Increased risk of serotonin syndrome. Monitor for symptoms of serotonin syndrome.
      Trimipramine Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Avoid combination or monitor for symptoms of serotonin syndrome and/or hypertensive crisis.
      Venlafaxine Increased risk of serotonin syndrome. Ensure adequate washout period between therapies to avoid toxicity. Concurrent therapy should be avoided.
      Vilazodone MAO Inhibitors may enhance the serotonergic effect of Selective Serotonin Reuptake Inhibitors. This may cause serotonin syndrome. Avoid combination.
      Zolmitriptan The MAO inhibitor, linezolid, may increase the serum concentration of zolmitriptan by decreasing its metabolism. Concomitant therapy and use of zolmitriptan within two weeks of discontinuing linezolid are contraindicated.
      Food Interactions
      • Take without regard to meals.
      Targets

      1. 23S rRNA

      Pharmacological action: yes
      Actions: inhibitor

      In prokaryotes, the 23S rRNA is part of the large subunit (the 50S) that joins with the 30S small subunit to create the functional 70S ribosome. The ribosome is comprised of 3 RNAs: the 23S, the 16S and the 5S ribosomal RNAs. The 23S and the 5S associate with their respective proteins to make up the large subunit of the ribosome, while the 16S RNA associates with its proteins to make up the small subunit.

      Gene Sequence: FASTA

      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
      3. Sinclair A, Arnold C, Woodford N: Rapid detection and estimation by pyrosequencing of 23S rRNA genes with a single nucleotide polymorphism conferring linezolid resistance in Enterococci. Antimicrob Agents Chemother. 2003 Nov;47(11):3620-2. Pubmed
      4. Meka VG, Pillai SK, Sakoulas G, Wennersten C, Venkataraman L, DeGirolami PC, Eliopoulos GM, Moellering RC Jr, Gold HS: Linezolid resistance in sequential Staphylococcus aureus isolates associated with a T2500A mutation in the 23S rRNA gene and loss of a single copy of rRNA. J Infect Dis. 2004 Jul 15;190(2):311-7. Epub 2004 Jun 9. Pubmed
      5. Zhu W, Tenover FC, Limor J, Lonsway D, Prince D, Dunne WM Jr, Patel JB: Use of pyrosequencing to identify point mutations in domain V of 23S rRNA genes of linezolid-resistant Staphylococcus aureus and Staphylococcus epidermidis. Eur J Clin Microbiol Infect Dis. 2007 Mar;26(3):161-5. Pubmed
      6. Colca JR, McDonald WG, Waldon DJ, Thomasco LM, Gadwood RC, Lund ET, Cavey GS, Mathews WR, Adams LD, Cecil ET, Pearson JD, Bock JH, Mott JE, Shinabarger DL, Xiong L, Mankin AS: Cross-linking in the living cell locates the site of action of oxazolidinone antibiotics. J Biol Chem. 2003 Jun 13;278(24):21972-9. Epub 2003 Apr 10. Pubmed
      7. Feng J, Lupien A, Gingras H, Wasserscheid J, Dewar K, Legare D, Ouellette M: Genome sequencing of linezolid-resistant Streptococcus pneumoniae mutants reveals novel mechanisms of resistance. Genome Res. 2009 Jul;19(7):1214-23. Epub 2009 Apr 6. Pubmed
      Enzymes

      1. Amine oxidase [flavin-containing] A

      Actions: inhibitor

      Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues. MAOA preferentially oxidizes biogenic amines such as 5-hydroxytryptamine (5-HT), norepinephrine and epinephrine

      UniProt ID: P21397 Link_out
      Gene: MAOA Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      References:
      1. Stevens DL, Dotter B, Madaras-Kelly K: A review of linezolid: the first oxazolidinone antibiotic. Expert Rev Anti Infect Ther. 2004 Feb;2(1):51-9. Pubmed
      2. Taylor JJ, Wilson JW, Estes LL: Linezolid and serotonergic drug interactions: a retrospective survey. Clin Infect Dis. 2006 Jul 15;43(2):180-7. Epub 2006 Jun 9. Pubmed

      2. Amine oxidase [flavin-containing] B

      Actions: inhibitor

      Catalyzes the oxidative deamination of biogenic and xenobiotic amines and has important functions in the metabolism of neuroactive and vasoactive amines in the central nervous system and peripheral tissues. MAOB preferentially degrades benzylamine and phenylethylamine

      UniProt ID: P27338 Link_out
      Gene: MAOB Link_out
      Protein Sequence: FASTA
      Gene Sequence: FASTA
      SNPs: SNPJam Report Link_out

      References:
      1. Stevens DL, Dotter B, Madaras-Kelly K: A review of linezolid: the first oxazolidinone antibiotic. Expert Rev Anti Infect Ther. 2004 Feb;2(1):51-9. Pubmed
      2. Taylor JJ, Wilson JW, Estes LL: Linezolid and serotonergic drug interactions: a retrospective survey. Clin Infect Dis. 2006 Jul 15;43(2):180-7. Epub 2006 Jun 9. Pubmed
      Comments
      Drug created on June 13, 2005 07:24 / Updated on February 08, 2013 16:19