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Identification
NameDemeclocycline
Accession NumberDB00618  (APRD00272)
TypeSmall Molecule
GroupsApproved
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
External Identifiers Not Available
Approved Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Declomycintablet150 mgoralWyeth Canada1996-10-252007-08-13Canada
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 Hydrochloridetablet150 mg/1oralCore Pharma, Llc2012-09-18Not applicableUs
Demeclocycline Hydrochloridetablet300 mg/1oralCore Pharma, Llc2012-09-18Not applicableUs
Approved Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing End
Demeclocycline Hydrochloridetablet150 mg/1oralCarilion Materials Management2010-04-01Not applicableUs
Demeclocycline Hydrochloridetablet, film coated150 mg/1oralGlobal Pharmaceuticals, Division of Impax Laboratories, Inc.2004-03-22Not applicableUs
Demeclocycline Hydrochloridetablet, film coated300 mg/1oralEpic Pharma, LLC2015-02-02Not applicableUs
Demeclocycline Hydrochloridetablet300 mg/1oralAmneal Pharmaceuticals of New York, LLC2008-02-27Not applicableUs
Demeclocycline Hydrochloridetablet, film coated150 mg/1oralEpic Pharma, LLC2015-02-02Not applicableUs
Demeclocycline Hydrochloridetablet150 mg/1oralAmneal Pharmaceuticals of New York, LLC2008-02-27Not applicableUs
Demeclocycline Hydrochloridetablet300 mg/1oralMajor Pharmaceuticals2010-11-19Not applicableUs
Demeclocycline Hydrochloridetablet300 mg/1oralAmerican Health Packaging2010-12-15Not applicableUs
Demeclocycline Hydrochloridetablet, film coated300 mg/1oralBarr Laboratories Inc.2005-01-04Not applicableUs
Demeclocycline Hydrochloridetablet150 mg/1oralAmerican Health Packaging2010-11-30Not applicableUs
Demeclocycline Hydrochloridetablet, film coated150 mg/1oralBarr Laboratories Inc.2005-01-04Not applicableUs
Demeclocycline Hydrochloridetablet, film coated150 mg/1oralVersa Pharm Incorporated2008-12-15Not applicableUs
Demeclocycline Hydrochloridetablet, film coated300 mg/1oralGolden State Medical Supply, Inc.2016-02-05Not applicableUs
Demeclocycline Hydrochloridetablet, film coated300 mg/1oralGlobal Pharmaceuticals, Division of Impax Laboratories, Inc.2004-03-22Not applicableUs
Demeclocycline Hydrochloridetablet, film coated300 mg/1oralVersa Pharm Incorporated2008-12-15Not applicableUs
Approved Over the Counter ProductsNot Available
Unapproved/Other Products Not Available
International Brands
NameCompany
DeclostatinNot Available
LedermycinTakeda
Brand mixturesNot Available
Salts
Name/CASStructureProperties
Demeclocycline hydrochloride
64-73-3
Thumb
  • InChI Key: OAPVUSSHCBRCOL-KBHRXELFSA-N
  • Monoisotopic Mass: 500.075321104
  • Average Mass: 501.314
DBSALT000040
Categories
UNII5R5W9ICI6O
CAS number127-33-3
WeightAverage: 464.853
Monoisotopic: 464.098643365
Chemical FormulaC21H21ClN2O8
InChI KeyInChIKey=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])[[email protected]](N(C)C)C(O)=C(C(N)=O)C(=O)[C@@]3(O)C(O)=C1C(=O)C1=C([[email protected]]2O)C(Cl)=CC=C1O
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 Parents
Substituents
  • Tetracycline
  • Tetracene
  • Naphthacene
  • Anthracene carboxylic acid or derivatives
  • Tetralin
  • Aryl ketone
  • 4-halophenol
  • Aralkylamine
  • Benzenoid
  • Aryl halide
  • Aryl chloride
  • Vinylogous acid
  • Tertiary alcohol
  • Tertiary aliphatic amine
  • Tertiary amine
  • Secondary alcohol
  • Primary carboxylic acid amide
  • Polyol
  • Ketone
  • Carboxamide group
  • Enol
  • Carboxylic acid derivative
  • Carboxylic acid amide
  • Hydrocarbon derivative
  • Organooxygen compound
  • Organonitrogen compound
  • Organochloride
  • Organohalogen compound
  • Carbonyl group
  • Amine
  • Alcohol
  • Aromatic homopolycyclic compound
Molecular FrameworkAromatic homopolycyclic compounds
External Descriptors
Pharmacology
IndicationUsed 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.
PharmacodynamicsDemeclocycline 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 actionDemeclocycline 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.
Related Articles
AbsorptionTetracyclines are readily absorbed.
Volume of distributionNot Available
Protein binding41-50%
Metabolism

Hepatic

Route of eliminationDemeclocycline 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 life10-17 hours
Clearance
  • Renal cl=35 mL/min/1.73 m2
ToxicityOral, rat: LD50 = 2372 mg/kg
Affected organisms
  • Enteric bacteria and other eubacteria
Pathways
PathwayCategorySMPDB ID
Demeclocycline Action PathwayDrug actionSMP00290
SNP Mediated EffectsNot Available
SNP Mediated Adverse Drug ReactionsNot Available
ADMET
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 )
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
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.
PatentsNot Available
Properties
StateSolid
Experimental Properties
PropertyValueSource
melting point220-223 °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 FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Spectra
Mass Spec (NIST)Not Available
SpectraNot Available
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
ATC CodesD06AA01J01AA01
AHFS Codes
  • 08:12.24
PDB Entries
FDA labelNot Available
MSDSDownload (51.5 KB)
Interactions
Drug Interactions
Drug
Aluminum hydroxideAluminum hydroxide can cause a decrease in the absorption of Demeclocycline resulting in a reduced serum concentration and potentially a decrease in efficacy.
AmdinocillinThe therapeutic efficacy of Amdinocillin can be decreased when used in combination with Demeclocycline.
AmoxicillinThe therapeutic efficacy of Amoxicillin can be decreased when used in combination with Demeclocycline.
AmpicillinThe therapeutic efficacy of Ampicillin can be decreased when used in combination with Demeclocycline.
AzidocillinThe therapeutic efficacy of Azidocillin can be decreased when used in combination with Demeclocycline.
AzlocillinThe therapeutic efficacy of Azlocillin can be decreased when used in combination with Demeclocycline.
BacampicillinThe therapeutic efficacy of Bacampicillin can be decreased when used in combination with Demeclocycline.
BenzylpenicillinThe therapeutic efficacy of Benzylpenicillin can be decreased when used in combination with Demeclocycline.
Bismuth SubcitrateThe serum concentration of Demeclocycline can be decreased when it is combined with Bismuth Subcitrate.
Bismuth SubsalicylateThe serum concentration of Demeclocycline can be decreased when it is combined with Bismuth Subsalicylate.
Calcium carbonateCalcium carbonate can cause a decrease in the absorption of Demeclocycline resulting in a reduced serum concentration and potentially a decrease in efficacy.
CarbenicillinThe therapeutic efficacy of Carbenicillin can be decreased when used in combination with Demeclocycline.
CloxacillinThe therapeutic efficacy of Cloxacillin can be decreased when used in combination with Demeclocycline.
ColesevelamColesevelam can cause a decrease in the absorption of Demeclocycline resulting in a reduced serum concentration and potentially a decrease in efficacy.
CyclacillinThe therapeutic efficacy of Cyclacillin can be decreased when used in combination with Demeclocycline.
DesmopressinThe therapeutic efficacy of Desmopressin can be decreased when used in combination with Demeclocycline.
DicloxacillinThe therapeutic efficacy of Dicloxacillin can be decreased when used in combination with Demeclocycline.
DicoumarolDemeclocycline may increase the anticoagulant activities of Dicoumarol.
FlucloxacillinThe therapeutic efficacy of Flucloxacillin can be decreased when used in combination with Demeclocycline.
HetacillinThe therapeutic efficacy of Hetacillin can be decreased when used in combination with Demeclocycline.
Iron DextranDemeclocycline can cause a decrease in the absorption of Iron Dextran resulting in a reduced serum concentration and potentially a decrease in efficacy.
LanthanumThe serum concentration of Demeclocycline can be decreased when it is combined with Lanthanum.
Magnesium oxideMagnesium oxide can cause a decrease in the absorption of Demeclocycline resulting in a reduced serum concentration and potentially a decrease in efficacy.
Magnesium SulfateMagnesium Sulfate can cause a decrease in the absorption of Demeclocycline resulting in a reduced serum concentration and potentially a decrease in efficacy.
MecamylamineDemeclocycline may increase the neuromuscular blocking activities of Mecamylamine.
MeticillinThe therapeutic efficacy of Meticillin can be decreased when used in combination with Demeclocycline.
MezlocillinThe therapeutic efficacy of Mezlocillin can be decreased when used in combination with Demeclocycline.
MipomersenDemeclocycline may increase the hepatotoxic activities of Mipomersen.
NafcillinThe therapeutic efficacy of Nafcillin can be decreased when used in combination with Demeclocycline.
OxacillinThe therapeutic efficacy of Oxacillin can be decreased when used in combination with Demeclocycline.
PhenoxymethylpenicillinThe therapeutic efficacy of Phenoxymethylpenicillin can be decreased when used in combination with Demeclocycline.
Picosulfuric acidThe therapeutic efficacy of Sodium picosulfate can be decreased when used in combination with Demeclocycline.
PiperacillinThe therapeutic efficacy of Piperacillin can be decreased when used in combination with Demeclocycline.
PivampicillinThe therapeutic efficacy of Pivampicillin can be decreased when used in combination with Demeclocycline.
PivmecillinamThe therapeutic efficacy of Pivmecillinam can be decreased when used in combination with Demeclocycline.
PorfimerDemeclocycline may increase the photosensitizing activities of Porfimer.
QuinaprilThe serum concentration of Demeclocycline can be decreased when it is combined with Quinapril.
Strontium ranelateThe serum concentration of Demeclocycline can be decreased when it is combined with Strontium ranelate.
SucralfateSucralfate can cause a decrease in the absorption of Demeclocycline resulting in a reduced serum concentration and potentially a decrease in efficacy.
Sucroferric OxyhydroxideThe serum concentration of Demeclocycline can be decreased when it is combined with Sucroferric Oxyhydroxide.
TicarcillinThe therapeutic efficacy of Ticarcillin can be decreased when used in combination with Demeclocycline.
VerteporfinDemeclocycline may increase the photosensitizing activities of Verteporfin.
Food Interactions
  • Avoid milk and multivalent ions.
  • Take on an empty stomach.

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
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 translational accuracy; many suppressors of streptomycin-dependent mutants of protein S12 are found in this protein, some but not all of which decrease translational accuracy (ram, ribosomal ambiguity muta...
Gene Name:
rpsD
Uniprot ID:
P0A7V8
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 ]
Comments
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Drug created on June 13, 2005 07:24 / Updated on April 10, 2014 13:40