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Identification
NameTetracycline
Accession NumberDB00759  (APRD00572)
Typesmall molecule
Groupsapproved
Description

Tetracycline is a broad spectrum polyketide antibiotic produced by the Streptomyces genus of Actinobacteria. It exerts a bacteriostatic effect on bacteria by binding reversible to the bacterial 30S ribosomal subunit and blocking incoming aminoacyl tRNA from binding to the ribosome acceptor site. It also binds to some extent to the bacterial 50S ribosomal subunit and may alter the cytoplasmic membrane causing intracellular components to leak from bacterial cells.

Structure
Thumb
Synonyms
SynonymLanguageCode
AnhydrotetracyclineNot AvailableNot Available
DeschlorobiomycinNot AvailableNot Available
Salts
Name/CAS Structure Properties
Tetracycline hydrochloride
64-75-5
Thumb
  • InChI Key: YCIHPQHVWDULOY-FMZCEJRJSA-N
  • Monoisotopic Mass: 480.129943493
  • Average Mass: 480.896
DBSALT000361
Brand names
NameCompany
AchromycinNot Available
Brand mixtures
Brand NameIngredients
HelidacMetronidazole + Bismuth subsalicylate + tetracycline hydrochloride
Categories
CAS number60-54-8
WeightAverage: 444.4346
Monoisotopic: 444.153265754
Chemical FormulaC22H24N2O8
InChI KeyOFVLGDICTFRJMM-WESIUVDSSA-N
InChI
InChI=1S/C22H24N2O8/c1-21(31)8-5-4-6-11(25)12(8)16(26)13-9(21)7-10-15(24(2)3)17(27)14(20(23)30)19(29)22(10,32)18(13)28/h4-6,9-10,15,25,27-28,31-32H,7H2,1-3H3,(H2,23,30)/t9-,10-,15-,21+,22-/m0/s1
IUPAC Name
(4S,4aS,5aS,6S,12aS)-4-(dimethylamino)-3,6,10,12,12a-pentahydroxy-6-methyl-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2-carboxamide
SMILES
[H][C@@]12C[C@@]3([H])C(=C(O)[C@]1(O)C(=O)C(C(N)=O)=C(O)[C@H]2N(C)C)C(=O)C1=C(O)C=CC=C1[C@@]3(C)O
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassAcenes and Derivatives
SubclassNaphthacenes
Direct parentNaphthacenes
Alternative parentsAnthracenecarboxylic Acids and Derivatives; Anthraquinones; Tetralins; Phenols and Derivatives; Tertiary Alcohols; Ketones; Polyols; Tertiary Amines; Primary Carboxylic Acid Amides; Enols; Carboxylic Acids; Polyamines; Enolates
Substituentsanthraquinone; tetralin; phenol derivative; benzene; tertiary alcohol; polyol; tertiary amine; carboxamide group; ketone; primary carboxylic acid amide; polyamine; enol; carboxylic acid derivative; enolate; carboxylic acid; amine; alcohol; carbonyl group; organonitrogen compound
Classification descriptionThis compound belongs to the naphthacenes. These are compounds containing a naphthacene moiety, which is a polyaromatic hydrocarbon made of four linearly fused benzene rings.
Pharmacology
IndicationUsed to treat bacterial infections such as Rocky Mountain spotted fever, typhus fever, tick fevers, Q fever, rickettsialpox and Brill-Zinsser disease. May be used to treat infections caused by Chlamydiae spp., B. burgdorferi (Lyme disease), and upper respiratory infections caused by typical (S. pneumoniae, H. influenzae, and M. catarrhalis) and atypical organisms (C. pneumoniae, M. pneumoniae, L. pneumophila). May also be used to treat acne. Tetracycline may be an alternative drug for people who are allergic to penicillin.
PharmacodynamicsTetracycline is a short-acting antibiotic that inhibits bacterial growth by inhibiting translation. It binds to the 30S ribosomal subunit and prevents the amino-acyl tRNA from binding to the A site of the ribosome. It also binds to some extent to the 50S ribosomal subunit. This binding is reversible in nature. Additionally tetracycline may alter the cytoplasmic membrane of bacteria causing leakage of intracellular contents, such as nucleotides, from the cell.
Mechanism of actionTetracycline passively diffuses through porin channels in the bacterial membrane and reversibly binds to the 30S ribosomal subunit, preventing binding of tRNA to the mRNA-ribosome complex, and thus interfering with protein synthesis.
AbsorptionBioavailability is less than 40% when administered via intramuscular injection, 100% intravenously, and 60-80% orally (fasting adults). Food and/or milk reduce GI absorption of oral preparations of tetracycline by 50% or more.
Volume of distributionNot Available
Protein binding20 - 67% protein bound
Metabolism

Not metabolized

Route of eliminationThey are concentrated by the liver in the bile and excreted in the urine and feces at high concentrations in a biologically active form.
Half life6-12 hours
ClearanceNot Available
ToxicityLD50=808mg/kg (orally in mice)
Affected organisms
  • Enteric bacteria and other eubacteria
Pathways
PathwayCategorySMPDB ID
Tetracycline Action PathwayDrug actionSMP00294
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.8006
Blood Brain Barrier - 0.9841
Caco-2 permeable + 0.7439
P-glycoprotein substrate Substrate 0.791
P-glycoprotein inhibitor I Non-inhibitor 0.8025
P-glycoprotein inhibitor II Non-inhibitor 0.7562
Renal organic cation transporter Non-inhibitor 0.9437
CYP450 2C9 substrate Non-substrate 0.7897
CYP450 2D6 substrate Non-substrate 0.9117
CYP450 3A4 substrate Substrate 0.6758
CYP450 1A2 substrate Non-inhibitor 0.9046
CYP450 2C9 substrate Non-inhibitor 0.9071
CYP450 2D6 substrate Non-inhibitor 0.9231
CYP450 2C19 substrate Non-inhibitor 0.9089
CYP450 3A4 substrate Non-inhibitor 0.8686
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.781
Ames test Non AMES toxic 0.9132
Carcinogenicity Non-carcinogens 0.9314
Biodegradation Not ready biodegradable 0.9906
Rat acute toxicity 2.7095 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.9968
hERG inhibition (predictor II) Non-inhibitor 0.7201
Pharmacoeconomics
Manufacturers
  • Heritage pharmaceuticals inc
  • Bristol laboratories inc div bristol myers co
  • Warner chilcott div warner lambert co
  • Pharmacia and upjohn co
  • Solvay pharmaceuticals
  • Wyeth ayerst laboratories
  • Apothecon inc div bristol myers squibb
  • Angus chemical co
  • Pfipharmecs div pfizer inc
  • On site therapeutics inc
  • Shire development inc
  • Lederle laboratories div american cyanamid co
  • Pfizer laboratories div pfizer inc
  • Storz ophthalmics inc sub american cyanamid co
  • Par pharmaceutical
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Par pharmaceutical inc
Packagers
Dosage forms
FormRouteStrength
CapsuleOral
OintmentOphthalmic
TabletOral
Prices
Unit descriptionCostUnit
Tetracycline hcl powder2.14USDg
Tetracycline powder1.37USDg
Tetracycline HCl 500 mg capsule0.2USDcapsule
Tetracycline HCl 250 mg capsule0.15USDcapsule
Apo-Tetra 250 mg Capsule0.07USDcapsule
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
melting point172.5 dec °CPhysProp
water solubility231 mg/L (at 25 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP-1.30HANSCH,C ET AL. (1995)
logS-3.12ADME Research, USCD
pKa3.3 (at 25 °C)SERJEANT,EP & DEMPSEY,B (1979)
Predicted Properties
PropertyValueSource
water solubility1.33e+00 g/lALOGPS
logP-0.56ALOGPS
logP-3.5ChemAxon
logS-2.5ALOGPS
pKa (strongest acidic)-2.2ChemAxon
pKa (strongest basic)8.24ChemAxon
physiological charge-1ChemAxon
hydrogen acceptor count9ChemAxon
hydrogen donor count6ChemAxon
polar surface area181.62ChemAxon
rotatable bond count2ChemAxon
refractivity114.19ChemAxon
polarizability43.03ChemAxon
number of rings4ChemAxon
bioavailability1ChemAxon
rule of fiveNoChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis Reference

Thomas F. McNamara, Nungavaram S. Ramamurthy, Lorne M. Golub, “Non-antibacterial tetracycline compositions possessing anti-collagenolytic properties and methods of preparing and using same.” U.S. Patent US4704383, issued May, 1963.

US4704383
General Reference
  1. Link
  2. Griffin MO, Fricovsky E, Ceballos G, Villarreal F: Tetracyclines: a pleitropic family of compounds with promising therapeutic properties. Review of the literature. Am J Physiol Cell Physiol. 2010 Sep;299(3):C539-48. Epub 2010 Jun 30. Pubmed
External Links
ResourceLink
KEGG DrugD00201
KEGG CompoundC06570
PubChem Compound5280962
PubChem Substance46506693
ChemSpider4510286
ChEBI27902
ChEMBLCHEMBL1440
Therapeutic Targets DatabaseDAP001527
PharmGKBPA451640
HETATC
Drug Product Database527777
RxListhttp://www.rxlist.com/cgi/generic2/tetcycl2.htm
Drugs.comhttp://www.drugs.com/tetracycline.html
WikipediaTetracycline
ATC CodesA01AB13D06AA04J01AA07S01AA09S02AA08S03AA02A01AB21S01AA02J01AA09D06AA02J01AA03
AHFS Codes
  • 08:12.24
  • 52:04.04
PDB Entries
FDA labelNot Available
MSDSshow(73.8 KB)
Interactions
Drug Interactions
Drug
AcenocoumarolTetracycline may increase the anticoagulant effect of acenocoumarol.
AcitretinIncreased risk of intracranial hypertension
AluminiumFormation of non-absorbable complexes
AmoxicillinPossible antagonism of action
AmpicillinPossible antagonism of action
AnisindioneTetracycline may increase the anticoagulant effect of anisindione.
AtovaquoneTetracycline may decrease the effect of atovaquone.
AttapulgiteFormation of non-absorbable complexes
AzlocillinPossible antagonism of action
AztreonamPossible antagonism of action
BacampicillinPossible antagonism of action
BenzylpenicillinPossible antagonism of action
BexaroteneTetracycline may enhance the adverse/toxic effect of Retinoic Acid Derivatives. Due to the risk of developing pseudotumor cerebri (also known as intracranial hypertension), avoid this combination of drugs if possible. If used concomitantly, monitor for evidence of this interaction (eg, dizziness, diplopia, headache).
Bismuth SubsalicylateFormation of non-absorbable complexes
CalciumFormation of non-absorbable complexes
Calcium AcetateCalcium salts such as calcium acetate may decrease the serum concentration of tetracycline derivatives such as tetracycline. In general, the coadministration of oral calcium salts and oral tetracycline derivatives should be avoided. Interactions may be able to be minimized by administering oral calcium preparations several hours before or after the dose of the oral tetracycline derivatives. Even with dose separation, therapy may still be compromised. Monitor for decreased therapeutic effect of oral tetracycline derivatives.
Calcium ChlorideCalcium salts such as calcium chloride may decrease the serum concentration of tetracycline derivatives such as tetracycline. In general, the coadministration of oral calcium salts and oral tetracycline derivatives should be avoided. Interactions may be able to be minimized by administering oral calcium preparations several hours before or after the dose of the oral tetracycline derivatives. Even with dose separation, therapy may still be compromised. Monitor for decreased therapeutic effect of oral tetracycline derivatives.
CarbenicillinPossible antagonism of action
ClavulanatePossible antagonism of action
CloxacillinPossible antagonism of action
ColesevelamBile acid sequestrants such as colesevelam may decrease the absorption of Tetracycline Derivatives. Monitor for decreased therapeutic effects of tetracycline derivatives if coadministered with a bile acid sequestrant. If these agents are used concomitantly, separate doses 2 or more hours to minimize the interaction. The manufacturer of colesevelam suggests that drugs should be administered at least 1 hour before or 4 hours after colesevelam.
CyclacillinPossible antagonism of action
DicloxacillinPossible antagonism of action
DicoumarolTetracycline may increase the anticoagulant effect of dicumarol.
DihydroxyaluminiumFormation of non-absorbable complexes
Ethinyl EstradiolThis anti-infectious agent could decrease the effect of the oral contraceptive
EtretinateIncreased risk of intracranial hypertension
FlucloxacillinPossible antagonism of action
HetacillinPossible antagonism of action
IronFormation of non-absorbable complexes
Iron DextranFormation of non-absorbable complexes
IsotretinoinIncreased risk of intracranial hypertension
MagnesiumFormation of non-absorbable complexes
Magnesium salicylateFormation of non-absorbable complexes
MestranolThis anti-infectious agent could decrease the effect of the oral contraceptive
Methicillin Acyl-SerinePossible antagonism of action
MethotrexateTetracycline may increase methotrexate toxicity.
MethoxyfluraneTetracycline may increase the renal toxicity of methoxyflurane.
MezlocillinPossible antagonism of action
NafcillinPossible antagonism of action
OxacillinPossible antagonism of action
Penicillin VPossible antagonism of action
PiperacillinPossible antagonism of action
PivampicillinPossible antagonism of action
PivmecillinamPossible antagonism of action
QuinaprilQuinapril may decrease the absorption of tetracycline.
TamsulosinTetracycline, a CYP3A4 inhibitor, may decrease the metabolism and clearance of Tamsulosin, a CYP3A4 substrate. Monitor for changes in therapeutic/adverse effects of Tamsulosin if Tetracycline is initiated, discontinued, or dose changed.
TazobactamPossible antagonism of action
TicarcillinTetracycline may reduce the effect of Ticarcillin by inhibiting bacterial growth. Ticarcillin exerts its effects on actively growing bacteria. To achieve synergism, Ticarcillin should be administered at least 2 hours prior to using Tetracycline.
TolterodineTetracycline may decrease the metabolism and clearance of Tolterodine. Adjust Tolterodine dose and monitor for efficacy and toxicity.
TramadolTetracycline may increase Tramadol toxicity by decreasing Tramadol metabolism and clearance.
TrazodoneThe CYP3A4 inhibitor, Tetracycline, may increase Trazodone efficacy/toxicity by decreasing Trazodone metabolism and clearance. Monitor for changes in Trazodone efficacy/toxicity if Tetracycline is initiated, discontinued or dose changed.
TretinoinDemeclocycline may increase the adverse effects of oral Tretinoin. Increase risk of pseudotumour cerebri. Concurrent therapy should be avoided.
Trisalicylate-cholineFormation of non-absorbable complexes
WarfarinTetracycline may increase the anticoagulant effect of warfarin.
ZincFormation of non-absorbable complexes
Food Interactions
  • Avoid milk, calcium containing dairy products, iron, antacids, or aluminium salts 2 hours before or 6 hours after using antacids while on this medication.
  • Take on empty stomach: 1 hour before or 2 hours after meals.
  • Take with a full glass of water.

Targets

1. 30S ribosomal protein S7

Kind: protein

Organism: Escherichia coli (strain K12)

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
30S ribosomal protein S7 P02359 Details

References:

  1. Buck MA, Cooperman BS: Single protein omission reconstitution studies of tetracycline binding to the 30S subunit of Escherichia coli ribosomes. Biochemistry. 1990 Jun 5;29(22):5374-9. Pubmed

2. 30S ribosomal protein S14

Kind: protein

Organism: Escherichia coli (strain K12)

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
30S ribosomal protein S14 P0AG59 Details

References:

  1. Buck MA, Cooperman BS: Single protein omission reconstitution studies of tetracycline binding to the 30S subunit of Escherichia coli ribosomes. Biochemistry. 1990 Jun 5;29(22):5374-9. Pubmed

3. 30S ribosomal protein S3

Kind: protein

Organism: Escherichia coli (strain K12)

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
30S ribosomal protein S3 P0A7V3 Details

References:

  1. Buck MA, Cooperman BS: Single protein omission reconstitution studies of tetracycline binding to the 30S subunit of Escherichia coli ribosomes. Biochemistry. 1990 Jun 5;29(22):5374-9. Pubmed

4. 30S ribosomal protein S8

Kind: protein

Organism: Escherichia coli (strain K12)

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
30S ribosomal protein S8 P0A7W7 Details

References:

  1. Buck MA, Cooperman BS: Single protein omission reconstitution studies of tetracycline binding to the 30S subunit of Escherichia coli ribosomes. Biochemistry. 1990 Jun 5;29(22):5374-9. Pubmed

5. 30S ribosomal protein S19

Kind: protein

Organism: Escherichia coli (strain K12)

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details
30S ribosomal protein S19 P0A7U3 Details

References:

  1. Buck MA, Cooperman BS: Single protein omission reconstitution studies of tetracycline binding to the 30S subunit of Escherichia coli ribosomes. Biochemistry. 1990 Jun 5;29(22):5374-9. Pubmed

6. 16S rRNA

Kind: nucleotide

Organism: Enteric bacteria and other eubacteria

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details

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. Nawaz M, Sung K, Khan SA, Khan AA, Steele R: Biochemical and molecular characterization of tetracycline-resistant Aeromonas veronii isolates from catfish. Appl Environ Microbiol. 2006 Oct;72(10):6461-6. Pubmed
  4. Domingue GJ Sr: Cryptic bacterial infection in chronic prostatitis: diagnostic and therapeutic implications. Curr Opin Urol. 1998 Jan;8(1):45-9. Pubmed
  5. Pringle M, Fellstrom C, Johansson KE: Decreased susceptibility to doxycycline associated with a 16S rRNA gene mutation in Brachyspira hyodysenteriae. Vet Microbiol. 2007 Jul 20;123(1-3):245-8. Epub 2007 Feb 25. Pubmed
  6. Rasmussen B, Noller HF, Daubresse G, Oliva B, Misulovin Z, Rothstein DM, Ellestad GA, Gluzman Y, Tally FP, Chopra I: Molecular basis of tetracycline action: identification of analogs whose primary target is not the bacterial ribosome. Antimicrob Agents Chemother. 1991 Nov;35(11):2306-11. Pubmed

7. Major prion protein

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Major prion protein P04156 Details

References:

  1. Chen X, Ji ZL, Chen YZ: TTD: Therapeutic Target Database. Nucleic Acids Res. 2002 Jan 1;30(1):412-5. Pubmed
  2. De Luigi A, Colombo L, Diomede L, Capobianco R, Mangieri M, Miccolo C, Limido L, Forloni G, Tagliavini F, Salmona M: The efficacy of tetracyclines in peripheral and intracerebral prion infection. PLoS One. 2008 Mar 26;3(3):e1888. Pubmed

Enzymes

1. Cytochrome P450 3A4

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: substrate inhibitor

Components

Name UniProt ID Details
Cytochrome P450 3A4 P08684 Details

References:

  1. Preissner S, Kroll K, Dunkel M, Senger C, Goldsobel G, Kuzman D, Guenther S, Winnenburg R, Schroeder M, Preissner R: SuperCYP: a comprehensive database on Cytochrome P450 enzymes including a tool for analysis of CYP-drug interactions. Nucleic Acids Res. 2010 Jan;38(Database issue):D237-43. Epub 2009 Nov 24. Pubmed

Carriers

1. Serum albumin

Kind: protein

Organism: Human

Pharmacological action: no

Components

Name UniProt ID Details
Serum albumin P02768 Details

References:

  1. Bratlid D, Bergan T: Displacement of albumin-bound antimicrobial agents by bilirubin. Pharmacology. 1976;14(5):464-72. Pubmed

Transporters

1. Solute carrier family 22 member 6

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 6 Q4U2R8 Details

References:

  1. Babu E, Takeda M, Narikawa S, Kobayashi Y, Yamamoto T, Cha SH, Sekine T, Sakthisekaran D, Endou H: Human organic anion transporters mediate the transport of tetracycline. Jpn J Pharmacol. 2002 Jan;88(1):69-76. Pubmed

2. Solute carrier family 22 member 8

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 8 Q8TCC7 Details

References:

  1. Babu E, Takeda M, Narikawa S, Kobayashi Y, Yamamoto T, Cha SH, Sekine T, Sakthisekaran D, Endou H: Human organic anion transporters mediate the transport of tetracycline. Jpn J Pharmacol. 2002 Jan;88(1):69-76. Pubmed

3. Solute carrier family 22 member 11

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 11 Q9NSA0 Details

References:

  1. Babu E, Takeda M, Narikawa S, Kobayashi Y, Yamamoto T, Cha SH, Sekine T, Sakthisekaran D, Endou H: Human organic anion transporters mediate the transport of tetracycline. Jpn J Pharmacol. 2002 Jan;88(1):69-76. Pubmed

4. Solute carrier family 22 member 7

Kind: protein

Organism: Human

Pharmacological action: unknown

Actions: inhibitor

Components

Name UniProt ID Details
Solute carrier family 22 member 7 Q9Y694 Details

References:

  1. Babu E, Takeda M, Narikawa S, Kobayashi Y, Yamamoto T, Cha SH, Sekine T, Sakthisekaran D, Endou H: Human organic anion transporters mediate the transport of tetracycline. Jpn J Pharmacol. 2002 Jan;88(1):69-76. Pubmed

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Drug created on June 13, 2005 07:24 / Updated on September 16, 2013 17:12