Demeclocycline

Identification

Name
Demeclocycline
Accession Number
DB00618
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.

Type
Small Molecule
Groups
Approved
Structure
Thumb
Weight
Average: 464.853
Monoisotopic: 464.098643365
Chemical Formula
C21H21ClN2O8
Synonyms
  • [4S-(4α,4aα,5aα,6β,12aα)]-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

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
Contraindications & Blackbox Warnings
Learn about our commercial Contraindications & Blackbox Warnings data.
Learn More
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 not a direct bactericidal agent; rather, it is a bacteriostatic drug that impairs bacterial growth. 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
inhibitor
UVasopressin V2 receptor
inhibitor
Humans
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
Adverse Effects
Learn about our commercial Adverse Effects data.
Learn More
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
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
AcenocoumarolThe risk or severity of bleeding can be increased when Demeclocycline is combined with Acenocoumarol.
AcitretinThe risk or severity of pseudotumor cerebri and elevated intracranial pressure can be increased when Acitretin is combined with Demeclocycline.
AlitretinoinThe risk or severity of pseudotumor cerebri and elevated intracranial pressure can be increased when Alitretinoin is combined with Demeclocycline.
AlmasilateAlmasilate can cause a decrease in the absorption of Demeclocycline resulting in a reduced serum concentration and potentially a decrease in efficacy.
AluminiumAluminium can cause a decrease in the absorption of Demeclocycline resulting in a reduced serum concentration and potentially a decrease in efficacy.
Aluminium phosphateAluminium phosphate can cause a decrease in the absorption of Demeclocycline resulting in a reduced serum concentration and potentially a decrease in efficacy.
Aluminum hydroxideAluminum hydroxide can cause a decrease in the absorption of Demeclocycline 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 Demeclocycline.
AmpicillinThe therapeutic efficacy of Ampicillin can be decreased when used in combination with Demeclocycline.
AtracuriumThe therapeutic efficacy of Atracurium can be increased when used in combination with Demeclocycline.
Additional Data Available
  • Extended Description
    Extended Description

    Extended description of the mechanism of action and particular properties of each drug interaction.

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  • Severity
    Severity

    A severity rating for each drug interaction, from minor to major.

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  • Evidence Level
    Evidence Level

    A rating for the strength of the evidence supporting each drug interaction.

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  • Action
    Action

    An effect category for each drug interaction. Know how this interaction affects the subject drug.

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Food Interactions
  • Avoid milk and dairy products.
  • Avoid multivalent ions.
  • Take on an empty stomach.

Products

Product Ingredients
IngredientUNIICASInChI Key
Demeclocycline hydrochloride29O079NTYT64-73-3GVSJQNRGSCOSNJ-KBHRXELFSA-N
Product Images
International/Other Brands
Declostatin / Ledermycin (Takeda)
Brand Name Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
DeclomycinTabletOralWyeth Ltd.1996-10-252007-08-13Canada
Declomycin - Tab 300mgTabletOralWyeth Ayerst Canada Inc.1997-10-152002-07-31Canada
Declomycin Tab 150mgTabletOralLederle Cyanamid Canada Inc.1977-12-311997-08-14Canada
Declomycin Tab 300mgTabletOralLederle Cyanamid Canada Inc.1966-12-311999-04-12Canada
Demeclocycline HydrochlorideTablet150 mg/1OralCore Pharma, Llc2012-08-282012-08-28Us
Demeclocycline HydrochlorideTablet300 mg/1OralCore Pharma, Llc2012-08-282012-08-28Us
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

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  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Generic Prescription Products
NameDosageStrengthRouteLabellerMarketing StartMarketing EndRegionImage
Demeclocycline HydrochlorideTablet, film coated300 mg/1OralPuraCap Laboratories LLC2017-10-07Not applicableUs
Demeclocycline HydrochlorideTablet, film coated150 mg/1OralImpax Generics2004-03-222013-12-31Us
Demeclocycline HydrochlorideTablet, film coated300 mg/1OralImpax Generics2004-03-222013-12-31Us
Demeclocycline HydrochlorideTablet150 mg/1OralCarilion Materials Management2010-04-01Not applicableUs
Demeclocycline HydrochlorideTablet150 mg/1OralAmneal Pharmaceuticals LLC2008-02-27Not applicableUs
Demeclocycline HydrochlorideTablet300 mg/1OralAmerican Health Packaging2010-12-09Not applicableUs
Demeclocycline HydrochlorideTablet300 mg/1OralMajor Pharmaceuticals2010-11-192013-09-30Us
Demeclocycline HydrochlorideTablet, film coated300 mg/1OralVersaPharm Inc - an Akorn Company2008-12-15Not applicableUs
Demeclocycline HydrochlorideTablet, film coated150 mg/1OralTeva Pharmaceuticals USA, Inc.2005-01-042020-03-31Us00555 0701 02 nlmimage10 5638ab65
Demeclocycline HydrochlorideTablet, film coated150 mg/1OralPuraCap Laboratories LLC2017-10-07Not applicableUs
Additional Data Available
  • Application Number
    Application Number

    A unique ID assigned by the FDA when a product is submitted for approval by the labeller.

    Learn more
  • Product Code
    Product Code

    A governmentally-recognized ID which uniquely identifies the product within its regulatory market.

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Categories

ATC Codes
J01AA01 — DemeclocyclineD06AA01 — DemeclocyclineJ01AA20 — 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 / Aralkylamines / Cyclohexenones / Aryl chlorides / Vinylogous acids / Tertiary alcohols
show 10 more
Substituents
1-hydroxy-2-unsubstituted benzenoid / Alcohol / Amine / Amino acid or derivatives / Anthracene carboxylic acid or derivatives / Aralkylamine / Aromatic homopolycyclic compound / Aryl chloride / Aryl halide / Aryl ketone
show 27 more
Molecular Framework
Aromatic homopolycyclic compounds
External Descriptors
tetracyclines (CHEBI:4392)

Chemical Identifiers

UNII
5R5W9ICI6O
CAS number
127-33-3
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

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]
Human Metabolome Database
HMDB0014756
KEGG Drug
D00290
PubChem Compound
54680690
PubChem Substance
46506314
ChemSpider
10482117
RxNav
3154
ChEBI
4392
ChEMBL
CHEMBL1591
ZINC
ZINC000100036924
Therapeutic Targets Database
DAP000402
PharmGKB
PA164745513
RxList
RxList Drug Page
Drugs.com
Drugs.com Drug Page
Wikipedia
Demeclocycline
MSDS
Download (51.5 KB)

Clinical Trials

Clinical Trials
PhaseStatusPurposeConditionsCount
4CompletedTreatmentOsteoporosis1
1Not Yet RecruitingDiagnosticNeoplasms, Brain1
0RecruitingTreatmentOsteomyelitis1
Not AvailableWithdrawnNot AvailableBreast Cancer1

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
TabletOral
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

Targets

1. 30S ribosomal protein
Kind
Group
Organism
Not Available
Pharmacological action
Yes
Actions
Inhibitor
Group which encompasses the subunits of the 30S ribosomal protein not specific to any organism.
References
  1. Griffin MO, Fricovsky E, Ceballos G, Villarreal F: Tetracyclines: a pleitropic family of compounds with promising therapeutic properties. Review of the literature. Am J Physiol Cell Physiol. 2010 Sep;299(3):C539-48. doi: 10.1152/ajpcell.00047.2010. Epub 2010 Jun 30. [PubMed:20592239]
  2. Chopra I, Roberts M: Tetracycline antibiotics: mode of action, applications, molecular biology, and epidemiology of bacterial resistance. Microbiol Mol Biol Rev. 2001 Jun;65(2):232-60 ; second page, table of contents. [PubMed:11381101]
Kind
Protein
Organism
Humans
Pharmacological action
Unknown
Actions
Inhibitor
General Function
Vasopressin receptor activity
Specific Function
Receptor for arginine vasopressin. The activity of this receptor is mediated by G proteins which activate adenylate cyclase. Involved in renal water reabsorption.
Gene Name
AVPR2
Uniprot ID
P30518
Uniprot Name
Vasopressin V2 receptor
Molecular Weight
40278.57 Da
References
  1. Narayen G, Mandal SN: Vasopressin receptor antagonists and their role in clinical medicine. Indian J Endocrinol Metab. 2012 Mar;16(2):183-91. doi: 10.4103/2230-8210.93734. [PubMed:22470853]
  2. Kortenoeven ML, Sinke AP, Hadrup N, Trimpert C, Wetzels JF, Fenton RA, Deen PM: Demeclocycline attenuates hyponatremia by reducing aquaporin-2 expression in the renal inner medulla. Am J Physiol Renal Physiol. 2013 Dec 15;305(12):F1705-18. doi: 10.1152/ajprenal.00723.2012. Epub 2013 Oct 23. [PubMed:24154696]
  3. Eric Fliers, Marta Korbonits , J.A. Romijn (2014). Clinical Neuroendocrinology, Volume 124 (1st ed.). Elsevier.

Drug created on June 13, 2005 07:24 / Updated on July 02, 2020 07:22

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