Identification

Name
Methacycline
Accession Number
DB00931  (APRD00137)
Type
Small Molecule
Groups
Approved, Investigational
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 Key
Methacycline hydrochloride9GJ0N7ZAP03963-95-9VZQARNDJLLWXGL-CCHMMTNSSA-N
International/Other Brands
Rondomycin
Categories
UNII
IR235I7C5P
CAS number
914-00-1
Weight
Average: 442.424
Monoisotopic: 442.137615676
Chemical Formula
C22H22N2O8
InChI Key
MHIGBKBJSQVXNH-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][[email protected]@]12[[email protected]@H](O)[[email protected]]3([H])C(=C)C4=C(C(O)=CC=C4)C(=O)C3=C(O)[[email protected]]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.

TargetActionsOrganism
A16S rRNA
inhibitor
Enteric bacteria and other eubacteria
Absorption

58% absorbed

Volume of distribution
Not Available
Protein binding

75-78% protein bound

Metabolism
Not Available
Route of elimination
Not Available
Half life

14 hours

Clearance
Not Available
Toxicity
Not Available
Affected organisms
  • Enteric bacteria and other eubacteria
Pathways
PathwayCategory
Methacycline Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
DrugInteractionDrug group
BCG vaccineThe therapeutic efficacy of BCG vaccine 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 Interactions
Not Available

References

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
KEGG Drug
D04972
KEGG Compound
C07654
PubChem Compound
54675785
PubChem Substance
46506631
ChemSpider
10468596
BindingDB
50046500
ChEBI
6805
ChEMBL
CHEMBL249837
Therapeutic Targets Database
DAP000883
PharmGKB
PA164750512
Wikipedia
Methacycline
ATC Codes
J01AA20 — Combinations of tetracyclinesJ01AA05 — Metacycline

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentOsteomyelitis1

Pharmacoeconomics

Manufacturers
  • Medpointe pharmaceuticals medpointe healthcare inc
Packagers
Not Available
Dosage forms
Not Available
Prices
Not Available
Patents
Not Available

Properties

State
Solid
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
Spectra
SpectrumSpectrum TypeSplash Key
Predicted MS/MS Spectrum - 10V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)Predicted LC-MS/MSNot Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)Predicted LC-MS/MSNot Available

Taxonomy

Description
This 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.
Kingdom
Organic compounds
Super Class
Phenylpropanoids and polyketides
Class
Tetracyclines
Sub Class
Not Available
Direct Parent
Tetracyclines
Alternative Parents
Naphthacenes / Anthracenecarboxylic acids and derivatives / Tetralins / Aryl ketones / 1-hydroxy-2-unsubstituted benzenoids / 1-hydroxy-4-unsubstituted benzenoids / Cyclohexenones / Vinylogous acids / Tertiary alcohols / Trialkylamines
show 8 more
Substituents
Tetracycline / Naphthacene / Tetracene / Anthracene carboxylic acid or derivatives / Tetralin / Aryl ketone / 1-hydroxy-4-unsubstituted benzenoid / 1-hydroxy-2-unsubstituted benzenoid / Cyclohexenone / Benzenoid
show 23 more
Molecular Framework
Aromatic homopolycyclic compounds
External Descriptors
tetracyclines (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 colloid...
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 November 07, 2017 01:44