DEMECLOCYCLINE

First approved in 1959

Details

Stereochemistry	ABSOLUTE
Molecular Formula	C21H21ClN2O8
Molecular Weight	464.853
Optical Activity	UNSPECIFIED
Defined Stereocenters	5 / 5
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

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)C4=C(O)C=CC(Cl)=C4[C@H]2O

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
Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/050261s101lbl.pdf
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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Bacterial 70S ribosome 179 Target ID: CHEMBL2363135 Sources: https://www.ncbi.nlm.nih.gov/pubmed/6423382	Inhibitor 8297

Conditions

Condition	Modality	Targets	Highest Phase	Product
Bacterial infections 234 Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/050261s101lbl.pdf	Curative		Approved 8429	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.

C_max

Value	Dose	Analyte	Population
2.4 mg/L OTHER https://www.medicines.org.uk/emc/product/499/smpc#PHARMACOKINETIC_PROPS	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 REVIEW https://academic.oup.com/jac/article/58/2/256/718565	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 REVIEW https://academic.oup.com/jac/article/58/2/256/718565	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 REVIEW https://academic.oup.com/jac/article/58/2/256/718565	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

T_1/2

Value	Dose	Analyte	Population
13 h DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/050261s101lbl.pdf	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 REVIEW https://academic.oup.com/jac/article/58/2/256/718565	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 REVIEW https://academic.oup.com/jac/article/58/2/256/718565	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

F_unbound

Value	Dose	Analyte	Population
60% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/050261s101lbl.pdf	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% REVIEW https://academic.oup.com/jac/article/58/2/256/718565	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% DRUG LABEL https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/050261s101lbl.pdf		DEMECLOCYCLINE plasma	Homo sapiens

Doses

Dose	Population	Adverse 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: https://pubmed.ncbi.nlm.nih.gov/103083/	unhealthy, 64 years n = 1 Health Status: unhealthy Condition: meningitis Age Group: 64 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/103083/	Disc. AE: Nephrotoxicity... AEs leading to discontinuation/dose reduction: Nephrotoxicity Sources: https://pubmed.ncbi.nlm.nih.gov/103083/
150 mg 4 times / day multiple, oral Dose: 150 mg, 4 times / day Route: oral Route: multiple Dose: 150 mg, 4 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/050261s101lbl.pdf	pregnant Health Status: pregnant Sex: F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/050261s101lbl.pdf	Disc. AE: Fetal damage... AEs leading to discontinuation/dose reduction: Fetal damage (grade 5) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/050261s101lbl.pdf
150 mg 4 times / day multiple, oral Dose: 150 mg, 4 times / day Route: oral Route: multiple Dose: 150 mg, 4 times / day Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/050261s101lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/050261s101lbl.pdf	Disc. AE: Diarrhea, Clostridium difficile... AEs leading to discontinuation/dose reduction: Diarrhea, Clostridium difficile (grade 5) Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/050261s101lbl.pdf

AEs

AE	Significance	Dose	Population
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: https://pubmed.ncbi.nlm.nih.gov/103083/	unhealthy, 64 years n = 1 Health Status: unhealthy Condition: meningitis Age Group: 64 years Sex: M Population Size: 1 Sources: https://pubmed.ncbi.nlm.nih.gov/103083/
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/050261s101lbl.pdf	pregnant Health Status: pregnant Sex: F Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/050261s101lbl.pdf
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: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/050261s101lbl.pdf	unhealthy Health Status: unhealthy Sources: https://www.accessdata.fda.gov/drugsatfda_docs/label/2012/050261s101lbl.pdf

Overview

CYP3A4	CYP2C9	CYP2D6	hERG

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
OAT3 642

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
OAT3 644	inhibitor 3277 Sources: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3490050/	yes

Sourcing

Vendor/Aggregator	ID	URL
ChEBI	CHEBI:4392	https://www.ebi.ac.uk/chebi/searchId.do?chebiId=CHEBI:4392
ZINC	ZINC000100036924	http://zinc15.docking.org/substances/ZINC000100036924
eMolecules	32176309	https://www.emolecules.com/cgi-bin/more?vid=32176309

PubMed

Title	Date	PubMed
Nephrogenic diabetes insipidus induced by demethylchlortetracycline (Declomycin).	1967 Nov	4966354
Nephrotoxicity of demethylchlortetracycline hydrochloride. A prospective study.	1967 Oct	4964507
Methacycline and demeclocycline in relation to sunlight.	1971 Apr 12	5107921
Peripheral neuropathy after disulfiram administration.	1971 Jun	4328367
Demeclocycline-induced nephrogenic diabetes insipidus. In-vivo and in-vitro studies.	1973 Nov	4356453
Effects of demethylchlortetracycline on cellular action of antidiuretic hormone in vitro.	1974 Apr	4368644
Demeclocycline treatment in the syndrome of inappropriate antidiuretic hormone secretion.	1975 Nov	173218
Correction of antidiuresis by demeclocycline.	1975 Oct 30	170519
Renal failure associated with demeclocycline in cirrhosis.	1977 Aug	407825
Demeclocycline and renal insufficiency.	1978 Feb 13	413940
Plasma demeclocycline levels and nephrotoxicity. Correlation in hyponatremic cirrhotic patients.	1980 Jun 27	6770106
Demeclocycline-induced phosphate diabetes in patients with inappropriate secretion of antidiuretic hormone.	1985 Dec 5	3932859
Inhibition of HIV-1 RNA-dependent DNA polymerase and cellular DNA polymerases alpha, beta and gamma by phosphonoformic acid and other drugs.	1988 Feb	2452149
Inhibition by antibiotic tetracyclines of rat cortical noradrenergic adenylate cyclase and amphetamine-induced hyperactivity.	1990 Nov	1965041
Demeclocycline-induced phosphate diabetes in a patient with inappropriate ADH secretion and systemic sarcoidosis.	1993	8450917
Syndrome of inappropriate antidiuretic hormone associated with vinorelbine therapy.	1998 Dec	9876812
Synergistic drug-cytokine induction of hepatocellular death as an in vitro approach for the study of inflammation-associated idiosyncratic drug hepatotoxicity.	2009 Jun 15	19362101
Hyponatremia in neurosurgical patients: clinical guidelines development.	2009 Nov	19834406

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

Demeclocycline protects cultured cerebellar granule neurons against glutamate toxicity at doses ranging between 80 and 150 μM.

Name

Type

Language

DEMECLOCYCLINE

Official Name

English

DEMETHYLCHLORTETRACYCLINE

Common Name

English

DEMECLOCYCLINE [USP MONOGRAPH]

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

Demeclocycline [WHO-DD]

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 IMPURITY B [EP IMPURITY]

Common Name

English

Classification Tree Code System Code

WHO-VATC

QJ01AA01