Identification

Name
Demeclocycline
Accession Number
DB00618  (APRD00272)
Type
Small Molecule
Groups
Approved
Description

A tetracycline analog having a 7-chloro and a 6-methyl. Because it is excreted more slowly than tetracycline, it maintains effective blood levels for longer periods of time. [PubChem]

Structure
Thumb
Synonyms
  • [4S-(4alpha,4Aalpha,5aalpha,6beta,12aalpha)]-7-chloro-4-(dimethylamino)1,4,4a,5,5a,6,11,12a-octahydro-3,6,10,12,12a-pentahydroxy-1,11-dioxo-2-naphthacenecarboxamide
  • 6-Demethyl-7-chlorotetracycline
  • 7-Chloro-6-demethyltetracycline
  • Demeclociclina
  • Demeclocycline
  • Demeclocyclinum
  • Demethylchlortetracyclin
  • Demethylchlortetracycline
  • DMCT
  • DMCTC
Product Ingredients
IngredientUNIICASInChI Key
Demeclocycline hydrochloride29O079NTYT64-73-3OAPVUSSHCBRCOL-KBHRXELFSA-N
Product Images
Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
DeclomycinTablet150 mgOralWyeth Ltd.1996-10-252007-08-13Canada
Declomycin - Tab 300mgTablet300 mgOralWyeth Ayerst Canada Inc.1997-10-152002-07-31Canada
Declomycin Tab 150mgTablet150 mgOralLederle Cyanamid Canada Inc.1977-12-311997-08-14Canada
Declomycin Tab 300mgTablet300 mgOralLederle Cyanamid Canada Inc.1966-12-311999-04-12Canada
Demeclocycline HydrochlorideTablet300 mg/1OralCore Pharma, Llc2012-08-282012-08-28Us
Demeclocycline HydrochlorideTablet150 mg/1OralCore Pharma, Llc2012-08-282012-08-28Us
Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Demeclocycline HydrochlorideTablet, film coated150 mg/1OralGolden State Medical Supply2016-02-05Not applicableUs
Demeclocycline HydrochlorideTablet, film coated300 mg/1OralVersa Pharm Incorporated2008-12-15Not applicableUs
Demeclocycline HydrochlorideTablet150 mg/1OralMajor2008-02-27Not applicableUs
Demeclocycline HydrochlorideTablet300 mg/1OralMajor2010-11-192018-08-13Us
Demeclocycline HydrochlorideTablet, film coated150 mg/1OralEpic Pharma, LLC2015-02-02Not applicableUs
Demeclocycline HydrochlorideTablet300 mg/1OralMajor2008-02-27Not applicableUs
Demeclocycline HydrochlorideTablet300 mg/1OralAmerincan Health Packaging2010-12-09Not applicableUs
Demeclocycline HydrochlorideTablet150 mg/1OralAmneal Pharmaceuticals2008-02-27Not applicableUs
Demeclocycline HydrochlorideTablet, film coated300 mg/1OralMarlex Pharmaceuticals Inc2016-07-01Not applicableUs
Demeclocycline HydrochlorideTablet, film coated150 mg/1OralVersa Pharm Incorporated2008-12-15Not applicableUs
International/Other Brands
Declostatin / Ledermycin (Takeda)
Categories
UNII
5R5W9ICI6O
CAS number
127-33-3
Weight
Average: 464.853
Monoisotopic: 464.098643365
Chemical Formula
C21H21ClN2O8
InChI Key
FMTDIUIBLCQGJB-SEYHBJAFSA-N
InChI
InChI=1S/C21H21ClN2O8/c1-24(2)14-7-5-6-10(16(27)12-9(25)4-3-8(22)11(12)15(6)26)18(29)21(7,32)19(30)13(17(14)28)20(23)31/h3-4,6-7,14-15,25-26,28-29,32H,5H2,1-2H3,(H2,23,31)/t6-,7-,14-,15-,21-/m0/s1
IUPAC Name
(4S,4aS,5aS,6S,12aS)-7-chloro-4-(dimethylamino)-3,6,10,12,12a-pentahydroxy-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydrotetracene-2-carboxamide
SMILES
[H][C@]12C[C@@]3([H])[C@H](N(C)C)C(O)=C(C(N)=O)C(=O)[C@@]3(O)C(O)=C1C(=O)C1=C([C@H]2O)C(Cl)=CC=C1O

Pharmacology

Indication

Used primarily to treat Lyme disease, acne, and bronchitis. Also indicated (but rarely used) to treat urinary tract infections, gum disease, malaria, and other bacterial infections such as gonorrhea and chlamydia. One of its other registered uses is the treatment of hyponatremia (low blood sodium concentration) due to the syndrome of inappropriate antidiuretic hormone (SIADH) where fluid restriction alone has been ineffective.

Associated Conditions
Pharmacodynamics

Demeclocycline is a tetracycline antibiotic active against the following microorganisms: Rickettsiae (Rocky Mountain spotted fever, typhus fever and the typhus group, Q fever, rickettsial pox, tick fevers), Mycoplasma pneumoniae (PPLO, Eaton agent), agents of psittacosis and ornithosis, agents of lymphogranulomavenereum and granuloma inguinale, the spirochetal agent of relapsing fever (Borrelia recurrentis), Haemophilus ducreyi (chancroid), Yersinia pestis, Pasteurella pestis and Pasteurella tularensis, Bartonella bacilliformis, Bacteroides species, Vibrio comma and Vibrio fetus, and Brucella species (in conjunction with streptomycin). Demeclocycline inhibits cell growth by inhibiting translation. Demeclocycline is lipophilic and can easily pass through the cell membrane or passively diffuses through porin channels in the bacterial membrane. Demeclocycline is bacteriostatic (it impairs bacterial growth but does not kill bacteria directly). Because it is excreted more slowly than tetracycline, it maintains effective blood levels for longer periods of time.

Mechanism of action

Demeclocycline inhibits cell growth by inhibiting translation. It binds (reversibly) to the 30S and 50S ribosomal subunit and prevents the amino-acyl tRNA from binding to the A site of the ribosome, which impairs protein synthesis by bacteria. The binding is reversible in nature. The use in SIADH actually relies on a side-effect of tetracycline antibiotics; many may cause diabetes insipidus (dehydration due to the inability to concentrate urine). It is not completely understood why demeclocycline impairs the action of antidiuretic hormone, but it is thought that it blocks the binding of the hormone to its receptor.

TargetActionsOrganism
A30S ribosomal protein S9
inhibitor
Escherichia coli (strain K12)
A30S ribosomal protein S4
inhibitor
Escherichia coli (strain K12)
Absorption

Tetracyclines are readily absorbed.

Volume of distribution
Not Available
Protein binding

41-50%

Metabolism

Hepatic

Route of elimination

Demeclocycline hydrochloride, like other tetracyclines, is concentrated in the liver and excreted into the bile where it is found in much higher concentrations than in the blood. Following a single 150 mg dose of demeclocycline hydrochloride in normal volunteers, 44% (n = 8) was excreted in urine and 13% and 46%, respectively, were excreted in feces in two patients within 96 hours as active drug.

Half life

10-17 hours

Clearance
  • Renal cl=35 mL/min/1.73 m2
Toxicity

Oral, rat: LD50 = 2372 mg/kg

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

Interactions

Drug Interactions
DrugInteraction
(R)-warfarinThe risk or severity of bleeding can be increased when Demeclocycline is combined with (R)-warfarin.
(S)-WarfarinThe risk or severity of bleeding can be increased when Demeclocycline is combined with (S)-Warfarin.
2,5-Dimethoxy-4-ethylthioamphetamineThe risk or severity of adverse effects can be increased when Demeclocycline is combined with 2,5-Dimethoxy-4-ethylthioamphetamine.
3,4-MethylenedioxyamphetamineThe risk or severity of adverse effects can be increased when Demeclocycline is combined with 3,4-Methylenedioxyamphetamine.
4-Bromo-2,5-dimethoxyamphetamineThe risk or severity of adverse effects can be increased when Demeclocycline is combined with 4-Bromo-2,5-dimethoxyamphetamine.
4-hydroxycoumarinThe risk or severity of bleeding can be increased when Demeclocycline is combined with 4-hydroxycoumarin.
4-MethoxyamphetamineThe risk or severity of adverse effects can be increased when Demeclocycline is combined with 4-Methoxyamphetamine.
5-methoxy-N,N-dimethyltryptamineThe risk or severity of adverse effects can be increased when Demeclocycline is combined with 5-methoxy-N,N-dimethyltryptamine.
7-NitroindazoleThe risk or severity of adverse effects can be increased when Demeclocycline is combined with 7-Nitroindazole.
7,8-Dichloro-1,2,3,4-tetrahydroisoquinolineThe risk or severity of adverse effects can be increased when Demeclocycline is combined with 7,8-Dichloro-1,2,3,4-tetrahydroisoquinoline.
Food Interactions
  • Avoid milk and multivalent ions.
  • Take on an empty stomach.

References

Synthesis Reference

McCormick, J.R.D., Hirsch, U., Jensen, E.R. and Sjolander, N.O.; U.S. Patent 2,878,289; March 17, 1959; assigned to American Cyanamid Company. Szumski, S.A.; U.S. Patent 3,012,946; December 12,1961; assigned to American Cyanamid Company. Goodman, J.J. and Matrishin, M.; U.S. Patent 3,019,172; assigned to American Cyanamid Company. Goodman, J.J.; U.S. Patent 3,050,446; August 21, 1962; assigned to American Cyanamid Company. Neidleman, S. L.; US. Patent 3,154,476; October 27,1964; assigned to Olin Mathieson Chemical Corporation.

General References
  1. De Troyer A, Demanet JC: Correction of antidiuresis by demeclocycline. N Engl J Med. 1975 Oct 30;293(18):915-8. [PubMed:170519]
External Links
Human Metabolome Database
HMDB0014756
KEGG Drug
D00290
PubChem Compound
54680690
PubChem Substance
46506314
ChemSpider
10482117
ChEBI
4392
ChEMBL
CHEMBL1591
Therapeutic Targets Database
DAP000402
PharmGKB
PA164745513
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Demeclocycline
ATC Codes
J01AA01 — DemeclocyclineJ01AA20 — Combinations of tetracyclinesD06AA01 — Demeclocycline
MSDS
Download (51.5 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
0RecruitingTreatmentOsteomyelitis1
1Not Yet RecruitingDiagnosticNeoplasms, Brain1
4CompletedTreatmentBone destruction1
Not AvailableWithdrawnNot AvailableCancer, Breast1

Pharmacoeconomics

Manufacturers
  • Lederle laboratories div american cyanamid co
  • Stiefel laboratories inc
  • Amneal pharmaceutical
  • Barr laboratories inc
  • Convenant pharma inc
  • Impax laboratories inc
  • Abbott laboratories pharmaceutical products div
  • Elkins sinn div ah robins co inc
  • John j ferrante
  • Heather drug co inc
  • Ivax pharmaceuticals inc sub teva pharmaceuticals usa
  • Laboratorios atral sarl
  • Mm mast and co
  • Mutual pharmaceutical co inc
  • Mylan pharmaceuticals inc
  • Purepac pharmaceutical co
  • Private formulations inc
  • Roxane laboratories inc
  • Sandoz inc
  • Superpharm corp
  • Valeant pharmaceuticals international
  • Warner chilcott inc
  • Watson laboratories inc
  • West ward pharmaceutical corp
  • Wyeth ayerst laboratories
  • Alpharma us pharmaceuticals division
  • Proter laboratory spa
Packagers
  • Amerisource Health Services Corp.
  • Amneal Pharmaceuticals
  • Barr Pharmaceuticals
  • Global Pharmaceuticals
  • Impax Laboratories Inc.
  • Murfreesboro Pharmaceutical Nursing Supply
  • Patheon Inc.
  • Pharmaceutical Utilization Management Program VA Inc.
  • Resource Optimization and Innovation LLC
  • Stonebridge Pharmaceuticals
  • Versapharm Inc.
Dosage forms
FormRouteStrength
TabletOral300 mg
TabletOral150 mg
TabletOral150 mg/1
TabletOral300 mg/1
Tablet, film coatedOral150 mg/1
Tablet, film coatedOral300 mg/1
Prices
Unit descriptionCostUnit
Declomycin 300 mg tablet22.29USD tablet
Demeclocycline 300 mg tablet17.06USD tablet
Declomycin 150 mg tablet12.31USD tablet
Demeclocycline 150 mg tablet9.42USD tablet
DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.
Patents
Not Available

Properties

State
Solid
Experimental Properties
PropertyValueSource
melting point (°C)220-223 °CNot Available
water solubility1520 mg/L (at 21 °C)YALKOWSKY,SH & DANNENFELSER,RM (1992)
logP0.2Not Available
logS-2.52ADME Research, USCD
Predicted Properties
PropertyValueSource
Water Solubility0.53 mg/mLALOGPS
logP-0.4ALOGPS
logP-3.2ChemAxon
logS-2.9ALOGPS
pKa (Strongest Acidic)-2.6ChemAxon
pKa (Strongest Basic)8.23ChemAxon
Physiological Charge-1ChemAxon
Hydrogen Acceptor Count9ChemAxon
Hydrogen Donor Count6ChemAxon
Polar Surface Area181.62 Å2ChemAxon
Rotatable Bond Count2ChemAxon
Refractivity114.35 m3·mol-1ChemAxon
Polarizability43.8 Å3ChemAxon
Number of Rings4ChemAxon
Bioavailability1ChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted ADMET features
PropertyValueProbability
Human Intestinal Absorption+0.8161
Blood Brain Barrier-0.9659
Caco-2 permeable+0.5
P-glycoprotein substrateSubstrate0.7387
P-glycoprotein inhibitor INon-inhibitor0.8835
P-glycoprotein inhibitor IINon-inhibitor0.8615
Renal organic cation transporterNon-inhibitor0.9375
CYP450 2C9 substrateNon-substrate0.8197
CYP450 2D6 substrateNon-substrate0.8739
CYP450 3A4 substrateSubstrate0.6802
CYP450 1A2 substrateNon-inhibitor0.9045
CYP450 2C9 inhibitorNon-inhibitor0.8995
CYP450 2D6 inhibitorNon-inhibitor0.9231
CYP450 2C19 inhibitorNon-inhibitor0.9025
CYP450 3A4 inhibitorNon-inhibitor0.8851
CYP450 inhibitory promiscuityLow CYP Inhibitory Promiscuity0.5128
Ames testNon AMES toxic0.8478
CarcinogenicityNon-carcinogens0.9182
BiodegradationNot ready biodegradable1.0
Rat acute toxicity1.8691 LD50, mol/kg Not applicable
hERG inhibition (predictor I)Weak inhibitor0.9949
hERG inhibition (predictor II)Non-inhibitor0.5633
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 GC-MS Spectrum - GC-MSPredicted GC-MSNot Available
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 / Aralkylamines / Cyclohexenones / Aryl chlorides / Vinylogous acids / Tertiary alcohols
show 10 more
Substituents
Tetracycline / Tetracene / Naphthacene / Anthracene carboxylic acid or derivatives / Tetralin / Aryl ketone / 1-hydroxy-2-unsubstituted benzenoid / Cyclohexenone / Aralkylamine / Aryl chloride
show 27 more
Molecular Framework
Aromatic homopolycyclic compounds
External Descriptors
tetracyclines (CHEBI:4392)

Targets

Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Trna binding
Specific Function
The C-terminal tail plays a role in the affinity of the 30S P site for different tRNAs. Mutations that decrease this affinity are suppressed in the 70S ribosome.
Gene Name
rpsI
Uniprot ID
P0A7X3
Uniprot Name
30S ribosomal protein S9
Molecular Weight
14856.105 Da
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:17139284]
  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:17016423]
Kind
Protein
Organism
Escherichia coli (strain K12)
Pharmacological action
Yes
Actions
Inhibitor
General Function
Translation repressor activity, nucleic acid binding
Specific Function
One of two assembly initiator proteins for the 30S subunit, it binds directly to 16S rRNA where it nucleates assembly of the body of the 30S subunit.With S5 and S12 plays an important role in trans...
Gene Name
rpsD
Uniprot ID
P0A7V8
Uniprot Name
30S ribosomal protein S4
Molecular Weight
23468.915 Da
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:17139284]
  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:17016423]

Drug created on June 13, 2005 07:24 / Updated on November 02, 2018 08:30