U.S. Department of Health & Human Services Divider Arrow National Institutes of Health Divider Arrow NCATS

Details

Stereochemistry ABSOLUTE
Molecular Formula C21H21ClN2O8
Molecular Weight 464.8538
Optical Activity UNSPECIFIED
Defined Stereocenters 5 / 5
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of DEMECLOCYCLINE

SMILES

CN(C)[C@@]1([H])[C@]2([H])C[C@@]3([H])C(=C([C@@]2(C(=O)C(=C1O)C(=N)O)O)O)C(=O)c4c(ccc(c4[C@@]3([H])O)Cl)O

InChI

InChIKey=FMTDIUIBLCQGJB-SEYHBJAFSA-N
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

HIDE SMILES / InChI

Description
Curator's Comment:: Description was created based on several sources, including https://www.drugs.com/ppa/demeclocycline.html | https://www.ncbi.nlm.nih.gov/pubmed/24154696

Demeclocycline hydrochloride is an antibiotic isolated from a mutant strain of Streptomyces aureofaciens. It inhibits protein synthesis by binding with the 30S and possibly the 50S ribosomal subunit(s) of susceptible bacteria. Demeclocycline has antimicrobial activity against a wide range of gram-negative and gram-positive organisms. Demeclocycline is indicated in the treatment of infections caused by susceptible strains of the designated microorganisms. Demeclocycline is currently used to treat hyponatremia in patients with the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Demeclocycline mainly attenuates hyponatremia in SIADH by reducing adenylate cyclase 5/6 expression and, consequently, cAMP generation, AQP2 gene transcription, and AQP2 abundance in the renal inner medulla, coinciding with a reduced vasopressin escape response in other collecting duct segments.

CNS Activity

Curator's Comment:: Demeclocycline is CNS active in rodents. No human data available.

Originator

Curator's Comment:: reference retrieved from http://www.drugfuture.com/chemdata/demeclocycline.html

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Curative
DEMECLOCYCLINE HYDROCHLORIDE

Approved Use

Demeclocycline HCl tablets, USP are indicated in the treatment of infections caused by susceptible strains of the designated microorganisms in the conditions below: Rocky Mountain spotted fever, typhus fever and the typhus group, Q fever, rickettsialpox and tick fevers caused by rickettsiae; Respiratory tract infections caused by Mycoplasma pneumoniae Lymphogranuloma venereum due to Chlamydia trachomatis Psittacosis (Ornithosis) due to Chlamydia psittaci Trachoma due to Chlamydia trachomatis, although the infectious agent is not always eliminated as judged by immunofluorescence Inclusion conjunctivitis caused by Chlamydia trachomatis Nongonococcal urethritis in adults caused by Ureaplasma urealyticum or Chlamydia trachomatis Relapsing fever due to Borrelia recurrentis Chancroid caused by Haemophilus ducreyi Plague due to Yersinia pestis Tularemia due to Francisella tularensis Cholera caused by Vibrio cholerae Campylobacter fetus infections cause by Campylobacter fetus Brucellosis due to Brucella species (in conjunction with streptomycin); Bartonellosis due to Bartonella bacilliformis Granuloma inguinale caused by Calymmatobacterium granulomatis Demeclocycline HCl tablets, USP are indicated for treatment of infections by the following gram-negative microorganisms, when bacteriologic testing indicates appropriate susceptibility to the drug: Escherichia coli Enterobacter aerogenes Shigella species Acinetobacter species Respiratory tract infections caused by Haemophilus influenzae Respiratory tract and urinary tract infections caused by Klebsiella species Demeclocycline HCl tablets, USP are indicated for treatment of infections caused by the following gram-positive microorganisms, when bacteriologic testing indicates appropriate susceptibility to the drug: Upper respiratory infections caused by Streptococcus pneumoniae Skin and skin structure infections caused by Staphylococcus aureus. (Note: Tetracyclines, including Demeclocycline, are not the drugs of choice in the treatment of any type of staphylococcal infection). When penicillin is contraindicated, tetracyclines, including Demeclocycline HCl, USP, are alternative drugs in the treatment of the following infections: Uncomplicated urethritis in men due to Neisseria gonorrhoeae, and for the treatment of other uncomplicated gonococcal infections Infections in women caused by Neisseria gonorrhoeae Syphilis caused by Treponema pallidum subspecies pallidum Yaws caused by Treponema pallidum subspecies pertenue Listeriosis due to Listeria monocytogenes Anthrax due to Bacillus anthracis Vincent’s infection caused by Fusobacterium fusiforme Actinomycosis caused by Actinomyces israelii Clostridial diseases caused by Clostridium species In acute intestinal amebiasis, Demeclocycline HCl, USP may be a useful adjunct to amebicides. In severe acne, Demeclocycline HCl, USP may be a useful adjunctive therapy. To reduce the development of drug-resistant bacteria and maintain the effectiveness of Demeclocycline HCl tablets, USP and other antibacterial drugs, Demeclocycline HCl tablets, USP should be used only to treat or prevent infections that are proven or strongly suspected to be caused by susceptible bacteria. When culture and susceptibility information are available they should be considered in selecting or modifying antibacterial therapy. In the absence of such data, local epidemiology and susceptibility patterns may contribute to the empiric selection of therapy.
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
2.4 mg/L
300 mg single, oral
dose: 300 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DEMECLOCYCLINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
1.2 mg/L
150 mg single, oral
dose: 150 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DEMECLOCYCLINE serum
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
1.7 mg/L
300 mg single, oral
dose: 300 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DEMECLOCYCLINE serum
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
2.5 mg/L
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DEMECLOCYCLINE serum
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
13 h
150 mg single, oral
dose: 150 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DEMECLOCYCLINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
13.5 h
300 mg single, oral
dose: 300 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DEMECLOCYCLINE serum
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
13 h
500 mg single, oral
dose: 500 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DEMECLOCYCLINE serum
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
60%
150 mg single, oral
dose: 150 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DEMECLOCYCLINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
17%
150 mg single, oral
dose: 150 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
DEMECLOCYCLINE serum
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
10%
DEMECLOCYCLINE plasma
Homo sapiens
Doses

Doses

DosePopulationAdverse events​
600 mg 4 times / day multiple, oral
Highest studied dose
Dose: 600 mg, 4 times / day
Route: oral
Route: multiple
Dose: 600 mg, 4 times / day
Sources:
unhealthy, 64 years
n = 1
Health Status: unhealthy
Condition: meningitis
Age Group: 64 years
Sex: M
Population Size: 1
Sources:
Disc. AE: Nephrotoxicity...
AEs leading to
discontinuation/dose reduction:
Nephrotoxicity
Sources:
150 mg 4 times / day multiple, oral
Dose: 150 mg, 4 times / day
Route: oral
Route: multiple
Dose: 150 mg, 4 times / day
Sources:
pregnant
Disc. AE: Fetal damage...
AEs leading to
discontinuation/dose reduction:
Fetal damage (grade 5)
Sources:
150 mg 4 times / day multiple, oral
Dose: 150 mg, 4 times / day
Route: oral
Route: multiple
Dose: 150 mg, 4 times / day
Sources:
unhealthy
Disc. AE: Diarrhea, Clostridium difficile...
AEs leading to
discontinuation/dose reduction:
Diarrhea, Clostridium difficile (grade 5)
Sources:
AEs

AEs

AESignificanceDosePopulation
Nephrotoxicity Disc. AE
600 mg 4 times / day multiple, oral
Highest studied dose
Dose: 600 mg, 4 times / day
Route: oral
Route: multiple
Dose: 600 mg, 4 times / day
Sources:
unhealthy, 64 years
n = 1
Health Status: unhealthy
Condition: meningitis
Age Group: 64 years
Sex: M
Population Size: 1
Sources:
Fetal damage grade 5
Disc. AE
150 mg 4 times / day multiple, oral
Dose: 150 mg, 4 times / day
Route: oral
Route: multiple
Dose: 150 mg, 4 times / day
Sources:
pregnant
Diarrhea, Clostridium difficile grade 5
Disc. AE
150 mg 4 times / day multiple, oral
Dose: 150 mg, 4 times / day
Route: oral
Route: multiple
Dose: 150 mg, 4 times / day
Sources:
unhealthy
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG

OverviewOther

Other InhibitorOther SubstrateOther Inducer

Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
yes
PubMed

PubMed

TitleDatePubMed
Nephrogenic diabetes insipidus induced by demethylchlortetracycline (Declomycin).
1967 Nov
Nephrotoxicity of demethylchlortetracycline hydrochloride. A prospective study.
1967 Oct
Methacycline and demeclocycline in relation to sunlight.
1971 Apr 12
Peripheral neuropathy after disulfiram administration.
1971 Jun
Demeclocycline-induced nephrogenic diabetes insipidus. In-vivo and in-vitro studies.
1973 Nov
Effects of demethylchlortetracycline on cellular action of antidiuretic hormone in vitro.
1974 Apr
Demeclocycline-induced diabetes insipidus.
1974 Aug 5
Demeclocycline treatment in the syndrome of inappropriate antidiuretic hormone secretion.
1975 Nov
Correction of antidiuresis by demeclocycline.
1975 Oct 30
Renal failure associated with demeclocycline in cirrhosis.
1977 Aug
Demeclocycline-induced renal failure.
1977 Jan 1
Demeclocycline and renal insufficiency.
1978 Feb 13
Nephrogenic diabetes insipidus due to demethylchlortetracycline hydrochloride in a child.
1978 Jan
Demeclocycline in the treatment of the syndrome of inappropriate secretion of antidiuretic hormone.
1979 Jun
Plasma demeclocycline levels and nephrotoxicity. Correlation in hyponatremic cirrhotic patients.
1980 Jun 27
Effect of prostaglandin inhibition on demeclocycline administration in conscious rats.
1980 Sep
[Organic renal insufficiency during treatment with demethylchlortetracycline].
1981 Jan 17
Serious hyponatremia in patients with cancer: management with demeclocycline.
1981 Jun 15
In vitro and in vivo susceptibility of atypical mycobacteria to various drugs.
1981 Sep-Oct
Demeclocycline-induced phosphate diabetes in patients with inappropriate secretion of antidiuretic hormone.
1985 Dec 5
Inhibition of HIV-1 RNA-dependent DNA polymerase and cellular DNA polymerases alpha, beta and gamma by phosphonoformic acid and other drugs.
1988 Feb
Inhibition by antibiotic tetracyclines of rat cortical noradrenergic adenylate cyclase and amphetamine-induced hyperactivity.
1990 Nov
Demeclocycline-induced phosphate diabetes in a patient with inappropriate ADH secretion and systemic sarcoidosis.
1993
Syndrome of inappropriate antidiuretic hormone associated with vinorelbine therapy.
1998 Dec
Irreversible nephrotoxicity from demeclocycline in the treatment of hyponatremia.
2002 Mar
Synergistic drug-cytokine induction of hepatocellular death as an in vitro approach for the study of inflammation-associated idiosyncratic drug hepatotoxicity.
2009 Jun 15
Hyponatremia in neurosurgical patients: clinical guidelines development.
2009 Nov
Patents

Sample Use Guides

Therapy should be continued for at least 24 to 48 hours after symptoms and fever have subsided. Concomitant therapy: Absorption of tetracyclines is impaired by antacids containing aluminum, calcium, or magnesium, and by iron-containing preparations. Foods and some dairy products also interfere with absorption. Oral forms of tetracycline should be given at least 1 hour before or 2 hours after meals. In patients with renal impairment: Tetracyclines should be used cautiously in patients with impaired renal function. Total dosage should be decreased by reduction of recommended individual doses and/or by extending time intervals between doses. In patients with liver impairment: Tetracyclines should be used cautiously in patients with impaired liver function. Total dosage should be decreased by reduction of recommended individual doses and/or by extending time intervals between doses. Administration of adequate amounts of fluid with the oral formulations of tetracyclines is recommended to wash down the drugs and reduce the risk of esophageal irritation and ulceration. Adults: Usual daily dose – Four divided doses of 150 mg each or two divided doses of 300 mg each. For pediatric patients above eight years of age: Usual daily dose, 7 to 13 mg per kg body weight per day, depending upon the severity of the disease, divided into two to four doses not to exceed adult dosage of 600 mg per day. Gonorrhea patients sensitive to penicillin may be treated with demeclocycline administered as an initial oral dose of 600 mg followed by 300 mg every 12 hours for four days to a total of 3 grams.
Route of Administration: Oral
Demeclocycline protects cultured cerebellar granule neurons against glutamate toxicity at doses ranging between 80 and 150 μM.
Name Type Language
DEMECLOCYCLINE
HSDB   INN   MART.   MI   USP   VANDF   WHO-DD  
INN  
Official Name English
CHLORTETRACYCLINE HYDROCHLORIDE IMPURITY B [EP]
Common Name English
DEMECLOCYCLINE [USP]
Common Name English
DEMETHYLCHLORTETRACYCLINE
Common Name English
DEMECLOCYCLINE [MART.]
Common Name English
2-NAPHTHACENECARBOXAMIDE, 7-CHLORO-4-(DIMETHYLAMINO)-1,4,4A,5,5A,6,11,12A-OCTAHYDRO-3,6,10,12,12A-PENTAHYDROXY-1,11-DIOXO-, (4S-(4.ALPHA.,4A.ALPHA.,5A.ALPHA.,6.BETA.,12A.ALPHA.))-
Common Name English
DEMECLOCYCLINE [MI]
Common Name English
7-CHLORO-4-(DIMETHYLAMINO)-1,4,4A,5,5A,6,11,12A-OCTAHYDRO-3,6,10,12,12A-PENTAHYDROXY-1,11-DIOXO-2-NAPHTHACENECARBOXAMIDE
Common Name English
DEMETHYLCHLORTETRACYCLINE [JAN]
Common Name English
DEMECLOCYCLINE [HSDB]
Common Name English
DEMECLOCYCLINE [VANDF]
Common Name English
DEMECLOCYCLINE [INN]
Common Name English
CHLORTETRACYCLINE HYDROCHLORIDE SPECIFIED IMPURITY B [EP]
Common Name English
DEMECLOCYCLINE [WHO-DD]
Common Name English
Classification Tree Code System Code
WHO-VATC QJ01AA01
Created by admin on Sat Jun 26 13:24:17 UTC 2021 , Edited by admin on Sat Jun 26 13:24:17 UTC 2021
NDF-RT N0000007948
Created by admin on Sat Jun 26 13:24:17 UTC 2021 , Edited by admin on Sat Jun 26 13:24:17 UTC 2021
WHO-VATC QD06AA01
Created by admin on Sat Jun 26 13:24:17 UTC 2021 , Edited by admin on Sat Jun 26 13:24:17 UTC 2021
NDF-RT N0000175505
Created by admin on Sat Jun 26 13:24:17 UTC 2021 , Edited by admin on Sat Jun 26 13:24:17 UTC 2021
NCI_THESAURUS C1595
Created by admin on Sat Jun 26 13:24:17 UTC 2021 , Edited by admin on Sat Jun 26 13:24:17 UTC 2021
NDF-RT N0000007948
Created by admin on Sat Jun 26 13:24:17 UTC 2021 , Edited by admin on Sat Jun 26 13:24:17 UTC 2021
WHO-ATC J01AA01
Created by admin on Sat Jun 26 13:24:17 UTC 2021 , Edited by admin on Sat Jun 26 13:24:17 UTC 2021
WHO-ATC D06AA01
Created by admin on Sat Jun 26 13:24:17 UTC 2021 , Edited by admin on Sat Jun 26 13:24:17 UTC 2021
LIVERTOX 278
Created by admin on Sat Jun 26 13:24:17 UTC 2021 , Edited by admin on Sat Jun 26 13:24:17 UTC 2021
Code System Code Type Description
ChEMBL
CHEMBL1591
Created by admin on Sat Jun 26 13:24:17 UTC 2021 , Edited by admin on Sat Jun 26 13:24:17 UTC 2021
PRIMARY
LACTMED
Demeclocycline
Created by admin on Sat Jun 26 13:24:17 UTC 2021 , Edited by admin on Sat Jun 26 13:24:17 UTC 2021
PRIMARY
RXCUI
3154
Created by admin on Sat Jun 26 13:24:17 UTC 2021 , Edited by admin on Sat Jun 26 13:24:17 UTC 2021
PRIMARY RxNorm
ECHA (EC/EINECS)
204-834-8
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PRIMARY
CAS
127-33-3
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PRIMARY
NCI_THESAURUS
C47980
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PRIMARY
DRUG CENTRAL
802
Created by admin on Sat Jun 26 13:24:17 UTC 2021 , Edited by admin on Sat Jun 26 13:24:17 UTC 2021
PRIMARY
DRUG BANK
DB00618
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PRIMARY
EPA CompTox
127-33-3
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PRIMARY
MERCK INDEX
M4160
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PRIMARY Merck Index
HSDB
3051
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PRIMARY
INN
917
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PRIMARY
FDA UNII
5R5W9ICI6O
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PRIMARY
WIKIPEDIA
DEMECLOCYCLINE
Created by admin on Sat Jun 26 13:24:17 UTC 2021 , Edited by admin on Sat Jun 26 13:24:17 UTC 2021
PRIMARY
EVMPD
SUB06963MIG
Created by admin on Sat Jun 26 13:24:17 UTC 2021 , Edited by admin on Sat Jun 26 13:24:17 UTC 2021
PRIMARY
MESH
D003707
Created by admin on Sat Jun 26 13:24:17 UTC 2021 , Edited by admin on Sat Jun 26 13:24:17 UTC 2021
PRIMARY