Identification

Generic Name
Metacycline
DrugBank Accession Number
DB00931
Background

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

Type
Small Molecule
Groups
Approved, Investigational
Structure
Thumb
Weight
Average: 442.424
Monoisotopic: 442.137615676
Chemical Formula
C22H22N2O8
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
  • Metaciclina
  • Metacycline
  • Methacycline
  • Methacyclinum
  • Methylenecycline
  • Tri-methacycline
External IDs
  • GS-2876

Pharmacology

Indication

For the treatment of acute bacterial exacerbations of chronic bronchitis

Pharmacology
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Contraindications & Blackbox Warnings
Contraindications
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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 ribosomal RNA
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

Adverse Effects
Adverseeffects
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Toxicity

Not Available

Pathways
PathwayCategory
Methacycline Action PathwayDrug action
Pharmacogenomic Effects/ADRs
Not Available

Interactions

Drug Interactions
This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
DrugInteraction
AcenocoumarolMetacycline may increase the anticoagulant activities of Acenocoumarol.
AcitretinThe risk or severity of pseudotumor cerebri can be increased when Acitretin is combined with Metacycline.
AlitretinoinThe risk or severity of pseudotumor cerebri can be increased when Alitretinoin is combined with Metacycline.
AlmasilateAlmasilate can cause a decrease in the absorption of Metacycline resulting in a reduced serum concentration and potentially a decrease in efficacy.
AluminiumAluminium can cause a decrease in the absorption of Metacycline resulting in a reduced serum concentration and potentially a decrease in efficacy.
Aluminium phosphateAluminium phosphate can cause a decrease in the absorption of Metacycline resulting in a reduced serum concentration and potentially a decrease in efficacy.
Aluminum hydroxideAluminum hydroxide can cause a decrease in the absorption of Metacycline resulting in a reduced serum concentration and potentially a decrease in efficacy.
AmoxicillinThe therapeutic efficacy of Amoxicillin can be decreased when used in combination with Metacycline.
AmpicillinThe therapeutic efficacy of Ampicillin can be decreased when used in combination with Metacycline.
AtracuriumThe therapeutic efficacy of Atracurium can be increased when used in combination with Metacycline.
Interactions
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Food Interactions
Not Available

Products

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Product Ingredients
IngredientUNIICASInChI Key
Metacycline hydrochloride9GJ0N7ZAP03963-95-9VZQARNDJLLWXGL-CCHMMTNSSA-N
International/Other Brands
Rondomycin

Categories

ATC Codes
J01AA05 — MetacyclineJ01AA20 — Combinations of tetracyclines
Drug Categories
Chemical TaxonomyProvided by Classyfire
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
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Substituents
1-hydroxy-2-unsubstituted benzenoid / 1-hydroxy-4-unsubstituted benzenoid / Alcohol / Amine / Amino acid or derivatives / Anthracene carboxylic acid or derivatives / Aromatic homopolycyclic compound / Aryl ketone / Benzenoid / Carbonyl group
show 23 more
Molecular Framework
Aromatic homopolycyclic compounds
External Descriptors
tetracyclines (CHEBI:6805)
Affected organisms
  • Enteric bacteria and other eubacteria

Chemical Identifiers

UNII
IR235I7C5P
CAS number
914-00-1
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][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)[C@H]2N(C)C

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. [Article]
  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. [Article]
KEGG Drug
D04972
KEGG Compound
C07654
PubChem Compound
54675785
PubChem Substance
46506631
ChemSpider
10468596
BindingDB
50046500
RxNav
6812
ChEBI
6805
ChEMBL
CHEMBL249837
ZINC
ZINC000085650610
Therapeutic Targets Database
DAP000883
PharmGKB
PA164750512
Wikipedia
Metacycline

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0TerminatedTreatmentOsteomyelitis1

Pharmacoeconomics

Manufacturers
  • Medpointe pharmaceuticals medpointe healthcare inc
Packagers
Not Available
Dosage Forms
FormRouteStrength
CapsuleOral300 MG
CapsuleOral
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

Targets

Drugtargets2
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Kind
Nucleotide
Organism
Enteric bacteria and other eubacteria
Pharmacological action
Yes
Actions
Inhibitor
In prokaryotes, the 16S rRNA is essential for recognizing the 5' end of mRNA and hence positioning it correctly on the ribosome. The 16S rRNA has a characteristic secondary structure in which half of the nucleotides are base-paired. The 16S rRNA sequence has been highly conserved and is often used for evolutionary and species comparative analysis.
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. [Article]
  2. Domingue GJ Sr: Cryptic bacterial infection in chronic prostatitis: diagnostic and therapeutic implications. Curr Opin Urol. 1998 Jan;8(1):45-9. [Article]
  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. [Article]
  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. [Article]

Carriers

Kind
Protein
Organism
Humans
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. doi: 10.1159/000136629. [Article]

Drug created at June 13, 2005 13:24 / Updated at April 03, 2021 09:41