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Identification
NameMethacycline
Accession NumberDB00931  (APRD00137)
Typesmall molecule
Groupsapproved
Description

A broad-spectrum semisynthetic antibiotic related to tetracycline but excreted more slowly and maintaining effective blood levels for a more extended period. [PubChem]

Structure
Thumb
Synonyms
SynonymLanguageCode
MetacyclineNot AvailableNot Available
MethacyclinNot AvailableNot Available
SaltsNot Available
Brand names
NameCompany
RondomycinNot Available
Brand mixturesNot Available
Categories
CAS number914-00-1
WeightAverage: 442.4187
Monoisotopic: 442.13761569
Chemical FormulaC22H22N2O8
InChI KeyInChIKey=IWFHNYCDKMICPE-LKTMJOCVSA-N
InChI
InChI=1S/C22H22N2O8/c1-7-8-5-4-6-9(25)11(8)16(26)12-10(7)17(27)14-15(24(2)3)18(28)13(21(23)31)20(30)22(14,32)19(12)29/h4-6,10,13-15,17,25,27,29,32H,1H2,2-3H3,(H2,23,31)/t10-,13?,14-,15+,17+,22+/m1/s1
IUPAC Name
(4S,4aR,5S,5aR,12aS)-4-(dimethylamino)-5,10,12,12a-tetrahydroxy-6-methylidene-1,3,11-trioxo-1,2,3,4,4a,5,5a,6,11,12a-decahydrotetracene-2-carboxamide
SMILES
CN(C)[C@H]1[C@@H]2[C@@H](O)[C@@H]3C(=C)C4=C(C(O)=CC=C4)C(=O)C3=C(O)[C@]2(O)C(=O)C(C(N)=O)C1=O
Mass SpecNot Available
Taxonomy
KingdomOrganic Compounds
SuperclassBenzenoids
ClassAcenes and Derivatives
SubclassAnthracenes
Direct parentAnthracenecarboxylic Acids and Derivatives
Alternative parentsAnthraquinones; Naphthalenecarboxamides; Tetralins; Cyclohexanols; Cyclohexanones; Phenols and Derivatives; Tertiary Alcohols; Tertiary Amines; Cyclic Alcohols and Derivatives; Primary Carboxylic Acid Amides; Polyols; Enolates; Polyamines; Carboxylic Acids; Enols
Substituents2-naphthalenecarboxamide; tetralin; cyclohexanol; cyclohexanone; phenol derivative; benzene; cyclic alcohol; tertiary alcohol; carboxamide group; secondary alcohol; polyol; ketone; tertiary amine; primary carboxylic acid amide; carboxylic acid derivative; polyamine; enolate; carboxylic acid; enol; alcohol; organonitrogen compound; amine; carbonyl group
Classification descriptionThis compound belongs to the anthracenecarboxylic acids and derivatives. These are organic compounds containing a carboxylic acid group (or a derivative thereof) attached to an anthracene ring system.
Pharmacology
IndicationFor the treatment of acute bacterial exacerbations of chronic bronchitis
PharmacodynamicsMethacycline is a tetracycline antibiotic. Similar to other tetracyclines, it has a wide spectrum of antimicrobial action. It is active against most Gram-positive bacteria (pneumococci, streptococci, staphylococci) and Gram-negative bacteria (E. coli, salmonella, shigella, etc.), and towards agents causing onithosis, psittacosis, trachoma, and some Protozoa. Like other tetracyclines, the general usefulness of methacycline has been reduced with the onset of bacterial resistance.
Mechanism of actionMethacycline, a tetracycline antibiotic, is a protein synthesis inhibitors, inhibiting the binding of aminoacyl-tRNA to the mRNA-ribosome complex. Methacycline inhibits cell growth by inhibiting translation. It binds to the 16S part of the 30S ribosomal subunit and prevents the amino-acyl tRNA from binding to the A site of the ribosome. The binding is reversible in nature. Tetracyclines also have been found to inhibit matrix metalloproteinases. This mechanism does not add to their antibiotic effects, but has led to extensive research on chemically modified tetracyclines or CMTs (like incyclinide) for the treatmet of rosacea, acne, and various types of neoplasms.
Absorption58% absorbed
Volume of distributionNot Available
Protein binding75-78% protein bound
Metabolism
Route of eliminationNot Available
Half life14 hours
ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Enteric bacteria and other eubacteria
PathwaysNot Available
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
Predicted ADMET features
Property Value Probability
Human Intestinal Absorption + 0.7183
Blood Brain Barrier - 0.9833
Caco-2 permeable - 0.8232
P-glycoprotein substrate Substrate 0.7092
P-glycoprotein inhibitor I Non-inhibitor 0.802
P-glycoprotein inhibitor II Non-inhibitor 0.9317
Renal organic cation transporter Non-inhibitor 0.9464
CYP450 2C9 substrate Non-substrate 0.8384
CYP450 2D6 substrate Non-substrate 0.8989
CYP450 3A4 substrate Substrate 0.6228
CYP450 1A2 substrate Non-inhibitor 0.9046
CYP450 2C9 substrate Non-inhibitor 0.9071
CYP450 2D6 substrate Non-inhibitor 0.923
CYP450 2C19 substrate Non-inhibitor 0.9026
CYP450 3A4 substrate Non-inhibitor 0.8309
CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.8019
Ames test Non AMES toxic 0.8374
Carcinogenicity Non-carcinogens 0.8692
Biodegradation Not ready biodegradable 0.9955
Rat acute toxicity 2.4401 LD50, mol/kg Not applicable
hERG inhibition (predictor I) Weak inhibitor 0.995
hERG inhibition (predictor II) Non-inhibitor 0.7584
Pharmacoeconomics
Manufacturers
  • Medpointe pharmaceuticals medpointe healthcare inc
PackagersNot Available
Dosage formsNot Available
PricesNot Available
PatentsNot Available
Properties
Statesolid
Experimental Properties
PropertyValueSource
water solubility7550 mg/L (at 21 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP-0.3Not Available
Predicted Properties
PropertyValueSource
water solubility7.32e-01 g/lALOGPS
logP0.39ALOGPS
logP-1.5ChemAxon
logS-2.8ALOGPS
pKa (strongest acidic)2.21ChemAxon
pKa (strongest basic)6.16ChemAxon
physiological charge-2ChemAxon
hydrogen acceptor count9ChemAxon
hydrogen donor count5ChemAxon
polar surface area178.46ChemAxon
rotatable bond count2ChemAxon
refractivity111.57ChemAxon
polarizability42.07ChemAxon
number of rings4ChemAxon
bioavailability1ChemAxon
rule of fiveYesChemAxon
Ghose filterNoChemAxon
Veber's ruleNoChemAxon
MDDR-like ruleNoChemAxon
Spectra
SpectraNot Available
References
Synthesis ReferenceNot Available
General Reference
  1. Agwuh KN, MacGowan A: Pharmacokinetics and pharmacodynamics of the tetracyclines including glycylcyclines. J Antimicrob Chemother. 2006 Aug;58(2):256-65. Epub 2006 Jul 1. Pubmed
  2. Li J, Chen L, Wang X, Jin H, Ding L, Zhang K, Zhang H: Determination of tetracyclines residues in honey by on-line solid-phase extraction high-performance liquid chromatography. Talanta. 2008 Jun 15;75(5):1245-52. Epub 2008 Jan 20. Pubmed
External Links
ResourceLink
KEGG DrugD04972
KEGG CompoundC07654
BindingDB50046500
Therapeutic Targets DatabaseDAP000883
PharmGKBPA164750512
WikipediaMethacycline
ATC CodesJ01AA05
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Interactions
Drug Interactions
Drug
AcitretinIncreased risk of intracranial hypertension
AmoxicillinPossible antagonism of action
AmpicillinPossible antagonism of action
BenzylpenicillinPossible antagonism of action
CalciumFormation of non-absorbable complexes
CarbenicillinPossible antagonism of action
ClavulanatePossible antagonism of action
CloxacillinPossible antagonism of action
DicloxacillinPossible antagonism of action
Ethinyl EstradiolThis anti-infectious agent could decrease the effect of the oral contraceptive
EtretinateIncreased risk of intracranial hypertension
FlucloxacillinPossible antagonism of action
Iron DextranFormation of non-absorbable complexes
IsotretinoinIncreased risk of intracranial hypertension
MagnesiumFormation of non-absorbable complexes
Penicillin VPossible antagonism of action
PiperacillinPossible antagonism of action
PivampicillinPossible antagonism of action
PivmecillinamPossible antagonism of action
Food InteractionsNot Available

1. 16S rRNA

Kind: nucleotide

Organism: Enteric bacteria and other eubacteria

Pharmacological action: yes

Actions: inhibitor

Components

Name UniProt ID Details

References:

  1. 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
  2. Domingue GJ Sr: Cryptic bacterial infection in chronic prostatitis: diagnostic and therapeutic implications. Curr Opin Urol. 1998 Jan;8(1):45-9. Pubmed
  3. 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
  4. Aminov RI, Chee-Sanford JC, Garrigues N, Mehboob A, Mackie RI: Detection of tetracycline resistance genes by PCR methods. Methods Mol Biol. 2004;268:3-13. Pubmed

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

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