Details
| Stereochemistry | ABSOLUTE |
| Molecular Formula | 2C21H21ClN2O8.3H2O |
| Molecular Weight | 983.752 |
| Optical Activity | UNSPECIFIED |
| Defined Stereocenters | 10 / 10 |
| E/Z Centers | 0 |
| Charge | 0 |
SHOW SMILES / InChI
SMILES
O.O.O.[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.[H][C@]56C[C@@]7([H])[C@H](N(C)C)C(O)=C(C(N)=O)C(=O)[C@@]7(O)C(O)=C5C(=O)C8=C(O)C=CC(Cl)=C8[C@H]6O
InChI
InChIKey=GCKOPPNKZABNEH-HZIPRYSESA-N
InChI=1S/2C21H21ClN2O8.3H2O/c2*1-24(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;;;/h2*3-4,6-7,14-15,25-26,28-29,32H,5H2,1-2H3,(H2,23,31);3*1H2/t2*6-,7-,14-,15-,21-;;;/m00.../s1
| Molecular Formula | H2O |
| Molecular Weight | 18.0153 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ACHIRAL |
| Additional Stereochemistry | No |
| Defined Stereocenters | 0 / 0 |
| E/Z Centers | 0 |
| Optical Activity | NONE |
| Molecular Formula | C21H21ClN2O8 |
| Molecular Weight | 464.853 |
| Charge | 0 |
| Count |
|
| Stereochemistry | ABSOLUTE |
| Additional Stereochemistry | No |
| Defined Stereocenters | 5 / 5 |
| E/Z Centers | 0 |
| Optical Activity | UNSPECIFIED |
DescriptionCurator'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
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.
Approval Year
Targets
| Primary Target | Pharmacology | Condition | Potency |
|---|---|---|---|
Target ID: CHEMBL2363135 |
Conditions
| Condition | Modality | Targets | Highest Phase | Product |
|---|---|---|---|---|
| Curative | DEMECLOCYCLINE HYDROCHLORIDE Approved UseDemeclocycline 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
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
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
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
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
| Value | Dose | Co-administered | Analyte | Population |
|---|---|---|---|---|
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
| 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: |
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 Health Status: pregnant Sex: F Sources: |
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 Health Status: unhealthy Sources: |
Disc. AE: Diarrhea, Clostridium difficile... AEs leading to discontinuation/dose reduction: Diarrhea, Clostridium difficile (grade 5) Sources: |
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: |
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 Health Status: pregnant Sex: F Sources: |
| 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 Health Status: unhealthy Sources: |
PubMed
| Title | Date | PubMed |
|---|---|---|
| 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
| Substance Class |
Chemical
Created
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| Record UNII |
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