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
6-Demethyl-6-deoxy-5-hydroxy-6-methylenetetracycline
6-Deoxy-6-demethyl-6-methylene-5-oxytetracycline
6-Methylene-5-hydroxytetracycline
6-Methylene-5-oxytetracycline
6-Methyleneoxytetracycline
Metacycline
Methacyclin
Methacyclinum
Methylenecycline
Tri-methacycline
External IDs GS-2876
Product Ingredients
IngredientUNIICASInChI KeyDetails
Methacycline hydrochloride9GJ0N7ZAP0 3963-95-9VZQARNDJLLWXGL-CCHMMTNSSA-NDetails
Approved Prescription ProductsNot Available
Approved Generic Prescription ProductsNot Available
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
RondomycinNot Available
Brand mixturesNot Available
Categories
UNIIIR235I7C5P
CAS number914-00-1
WeightAverage: 442.424
Monoisotopic: 442.137615676
Chemical FormulaC22H22N2O8
InChI KeyMHIGBKBJSQVXNH-IWVLMIASSA-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/h4-6,10,14-15,17,25,27-29,32H,1H2,2-3H3,(H2,23,31)/t10-,14-,15+,17+,22+/m1/s1
IUPAC Name
(4S,4aR,5S,5aR,12aS)-4-(dimethylamino)-3,5,10,12,12a-pentahydroxy-6-methylidene-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2-carboxamide
SMILES
[H][C@@]12[C@@H](O)[C@]3([H])C(=C)C4=C(C(O)=CC=C4)C(=O)C3=C(O)[C@]1(O)C(=O)C(C(N)=O)=C(O)[[email protected]]2N(C)C
Pharmacology
Indication

For the treatment of acute bacterial exacerbations of chronic bronchitis

Structured Indications Not Available
Pharmacodynamics

Methacycline 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 action

Methacycline, 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.

TargetKindPharmacological actionActionsOrganismUniProt ID
16S rRNANucleotideyes
inhibitor
Enteric bacteria and other eubacterianot applicabledetails
Related Articles
Absorption

58% absorbed

Volume of distributionNot Available
Protein binding

75-78% protein bound

MetabolismNot Available
Route of eliminationNot Available
Half life

14 hours

ClearanceNot Available
ToxicityNot Available
Affected organisms
  • Enteric bacteria and other eubacteria
Pathways
PathwayCategorySMPDB ID
Methacycline Action PathwayDrug actionSMP00727
Pharmacogenomic Effects/ADRs Not Available
Interactions
Drug Interactions
DrugInteractionDrug group
BCG vaccineThe therapeutic efficacy of Bcg can be decreased when used in combination with Methacycline.Investigational
Picosulfuric acidThe therapeutic efficacy of Picosulfuric acid can be decreased when used in combination with Methacycline.Approved
Food InteractionsNot Available
References
Synthesis ReferenceNot Available
General References
  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:16816396 ]
  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. doi: 10.1016/j.talanta.2008.01.027. Epub 2008 Jan 20. [PubMed:18585209 ]
External Links
ATC CodesJ01AA20 — Combinations of tetracyclinesJ01AA05 — Metacycline
AHFS CodesNot Available
PDB EntriesNot Available
FDA labelNot Available
MSDSNot Available
Clinical Trials
Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentOsteomyelitis1
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 Solubility1.14 mg/mLALOGPS
logP-0.46ALOGPS
logP-3.5ChemAxon
logS-2.6ALOGPS
pKa (Strongest Acidic)2.88ChemAxon
pKa (Strongest Basic)7.44ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count9ChemAxon
Hydrogen Donor Count6ChemAxon
Polar Surface Area181.62 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity113.67 m3·mol-1ChemAxon
Polarizability41.95 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.7183
Blood Brain Barrier-0.9833
Caco-2 permeable-0.8232
P-glycoprotein substrateSubstrate0.7092
P-glycoprotein inhibitor INon-inhibitor0.802
P-glycoprotein inhibitor IINon-inhibitor0.9317
Renal organic cation transporterNon-inhibitor0.9464
CYP450 2C9 substrateNon-substrate0.8384
CYP450 2D6 substrateNon-substrate0.8989
CYP450 3A4 substrateSubstrate0.6228
CYP450 1A2 substrateNon-inhibitor0.9046
CYP450 2C9 inhibitorNon-inhibitor0.9071
CYP450 2D6 inhibitorNon-inhibitor0.923
CYP450 2C19 inhibitorNon-inhibitor0.9026
CYP450 3A4 inhibitorNon-inhibitor0.8309
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.8019
Ames testNon AMES toxic0.8374
CarcinogenicityNon-carcinogens0.8692
BiodegradationNot ready biodegradable0.9955
Rat acute toxicity2.4401 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.995
hERG inhibition (predictor II)Non-inhibitor0.7584
ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397 )
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
Taxonomy
DescriptionThis compound belongs to the class of organic compounds known as tetracyclines. These are polyketides having an octahydrotetracene-2-carboxamide skeleton, substituted with many hydroxy and other groups.
KingdomOrganic compounds
Super ClassPhenylpropanoids and polyketides
ClassTetracyclines
Sub ClassNot Available
Direct ParentTetracyclines
Alternative ParentsNaphthacenes / Anthracenecarboxylic acids and derivatives / Tetralins / Aryl ketones / Cyclohexenones / 1-hydroxy-2-unsubstituted benzenoids / 1-hydroxy-4-unsubstituted benzenoids / Vinylogous acids / Tertiary alcohols / Secondary alcohols
SubstituentsTetracycline / Naphthacene / Tetracene / Anthracene carboxylic acid or derivatives / Tetralin / Aryl ketone / 1-hydroxy-4-unsubstituted benzenoid / 1-hydroxy-2-unsubstituted benzenoid / Cyclohexenone / Phenol
Molecular FrameworkAromatic homopolycyclic compounds
External Descriptorstetracyclines (CHEBI:6805 )

Targets

1. 16S rRNA
Kind
Nucleotide
Organism
Enteric bacteria and other eubacteria
Pharmacological action
yes
Actions
inhibitor
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:17021193 ]
  2. Domingue GJ Sr: Cryptic bacterial infection in chronic prostatitis: diagnostic and therapeutic implications. Curr Opin Urol. 1998 Jan;8(1):45-9. [PubMed:17035842 ]
  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:17428623 ]
  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:15156014 ]

Carriers

Kind
Protein
Organism
Human
Pharmacological action
no
General Function:
Toxic substance binding
Specific Function:
Serum albumin, the main protein of plasma, has a good binding capacity for water, Ca(2+), Na(+), K(+), fatty acids, hormones, bilirubin and drugs. Its main function is the regulation of the colloidal osmotic pressure of blood. Major zinc transporter in plasma, typically binds about 80% of all plasma zinc.
Gene Name:
ALB
Uniprot ID:
P02768
Uniprot Name:
Serum albumin
Molecular Weight:
69365.94 Da
References
  1. Bratlid D, Bergan T: Displacement of albumin-bound antimicrobial agents by bilirubin. Pharmacology. 1976;14(5):464-72. [PubMed:1031216 ]
Drug created on June 13, 2005 07:24 / Updated on July 18, 2017 16:54