Demeclocycline
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| Systematic (IUPAC) name |
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(2E,4S,4aS,5aS,6S,12aS)-2-[amino(hydroxy)methylidene]-7-chloro-4-(dimethylamino)-6,10,11,12a-tetrahydroxy-1,2,3,4,4a,5,5a,6,12,12a-decahydrotetracene-1,3,12-trione
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| Clinical data |
| Trade names |
Declomycin |
| AHFS/Drugs.com |
monograph |
| MedlinePlus |
a682103 |
Pregnancy
category |
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Routes of
administration |
Oral |
| Legal status |
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| Pharmacokinetic data |
| Bioavailability |
60–80% |
| Protein binding |
41–50% |
| Metabolism |
Hepatic |
| Biological half-life |
10–17 hours |
| Excretion |
Renal |
| Identifiers |
| CAS Number |
127-33-3 Y
64-73-3 (HCl) |
| ATC code |
D06AA01 (WHO) J01AA01 |
| PubChem |
CID 5311063 |
| DrugBank |
DB00618 Y |
| ChemSpider |
10482117 Y |
| UNII |
5R5W9ICI6O Y |
| KEGG |
D03680 Y |
| ChEBI |
CHEBI:4392 Y |
| ChEMBL |
CHEMBL1591 Y |
| Synonyms |
RP-10192 |
| Chemical data |
| Formula |
C21H21ClN2O8 |
| Molar mass |
464.853 g/mol |
SMILES
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CN(C)[C@@H]1C(\O)=C(\C(N)=O)C(=O)[C@@]2(O)C(/O)=C3/C(=O)c4c(O)ccc(Cl)c4[C@@H](O)[C@H]3C[C@@H]12
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InChI
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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 Y
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Key:FMTDIUIBLCQGJB-SEYHBJAFSA-N Y
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| (verify) |
Demeclocycline (INN, BAN) (brand names Declomycin, Declostatin, Ledermycin, Bioterciclin, Deganol, Deteclo), also known as demeclocycline hydrochloride (USAN) (brand names Detravis, Meciclin, Mexocine, Clortetrin), is a semisynthetic tetracycline antibiotic which was derived from a strain of Streptomyces aureofaciens.[1][2][3]
Contents
- 1 Uses
- 2 Contraindications
- 3 Side effects and interactions
- 4 Mechanism of action
- 5 References
Uses
It is officially indicated for the treatment of various types of bacterial infections.[4] It is used as an antibiotic in the treatment of Lyme disease, acne, and bronchitis.[citation needed] Resistance, though, is gradually becoming more common, and demeclocycline is now rarely used for infections.
It is widely used (though off-label in many countries) in the treatment of hyponatremia (low blood sodium concentration) due to the syndrome of inappropriate antidiuretic hormone (SIADH) when fluid restriction alone has been ineffective.[5] Physiologically, this works by reducing the responsiveness of the collecting tubule cells to ADH.
The use in SIADH actually relies on a side effect; demeclocycline induces nephrogenic diabetes insipidus (dehydration due to the inability to concentrate urine).[5] The use of demeclocycline in SIADH was first reported in 1975,[6] and, in 1978, a larger study found it to be more effective and better tolerated than lithium carbonate, the only available treatment at the time.[7] Demeclocycline has since been the drug of choice for treating SIADH, although it may be superseded as vasopressin receptor antagonists, such as tolvaptan, become available.[7]
Contraindications
Like other tetracyclines, demeclocycline is contraindicated in children and pregnant or nursing women. All members of this class interfere with bone development and may discolour teeth.[8]
Side effects and interactions
These are similar to those of other tetracyclines. Skin reactions with sunlight have been reported.[7] Demeclocycline is unique in that it is the only tetracycline known to cause nephrogenic diabetes insipidus.
Tetracyclines bind to cations, such as calcium, iron (when given orally), and magnesium, rendering them insoluble and inabsorbable for the gastrointestinal tract. Demeclocycline should not be taken with food (particularly milk and other dairy products) or antacids.[8]
Mechanism of action
As with related tetracycline antibiotics, demeclocycline acts by binding to the 30S ribosomal subunit to inhibit binding of aminoacyl tRNA which impairs protein synthesis by bacteria. It is bacteriostatic (it impairs bacterial growth, but does not kill bacteria directly).
Demeclocycline inhibits the renal action of antidiuretic hormone by interfering with the intracellular second messenger cascade (specifically, inhibiting adenylyl cyclase activation) after the hormone binds to vasopressin V2 receptors in the kidney.[9][10][11] Exactly how demeclocycline does this has yet to be elucidated, however.[11]
References
- ^ "demeclocycline" at Dorland's Medical Dictionary
- ^ J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 356–. ISBN 978-1-4757-2085-3.
- ^ I.K. Morton; Judith M. Hall (6 December 2012). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. pp. 92–. ISBN 978-94-011-4439-1.
- ^ "DailyMed: About DailyMed". Retrieved 2008-12-20.
- ^ a b Goh KP (May 2004). "Management of hyponatremia". American Family Physician 69 (10): 2387–94. PMID 15168958.
- ^ Cherrill DA, Stote RM, Birge JR, Singer I (November 1975). "Demeclocycline treatment in the syndrome of inappropriate antidiuretic hormone secretion". Annals of Internal Medicine 83 (5): 654–6. doi:10.7326/0003-4819-83-5-654. PMID 173218.
- ^ a b c Tolstoi LG (2002). "A brief review of drug-induced syndrome of inappropriate secretion of antidiuretic hormone". Medscape Pharmacotherapy 4 (1). Retrieved on October 27, 2008.
- ^ a b Lexi-Comp (August 2008). "Demeclocycline". The Merck Manual Professional. Retrieved on October 27, 2008.
- ^ Eric Fliers; Marta Korbonits; J.A. Romijn (28 August 2014). Clinical Neuroendocrinology. Elsevier Science. pp. 43–. ISBN 978-0-444-62612-7.
- ^ L. Kovács; B. Lichardus (6 December 2012). Vasopressin: Disturbed Secretion and Its Effects. Springer Science & Business Media. pp. 180–. ISBN 978-94-009-0449-1.
- ^ a b Ajay K. Singh; Gordon H. Williams (12 January 2009). Textbook of Nephro-Endocrinology. Academic Press. pp. 251–. ISBN 978-0-08-092046-7.
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Antibiotics and chemotherapeutics for dermatological use (D06)
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| Antibiotics |
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Tetracycline and derivatives
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- Demeclocycline
- Chlortetracycline
- Oxytetracycline
- Tetracycline
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Others
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- Amphenicol: Chloramphenicol
- Aminoglycosides: Neomycin
- Gentamicin
- Amikacin
- Streptogramin: Virginiamycin
- other: Fusidic acid
- Bacitracin
- Tyrothricin
- Mupirocin
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|
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| Chemotherapeutics |
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Sulfonamides
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- Silver sulfadiazine
- Sulfathiazole
- Mafenide
- Sulfamethizole
- Sulfanilamide
- Sulfamerazine
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Antivirals
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- Aciclovir
- Penciclovir
- Idoxuridine
- Edoxudine
- Imiquimod
- Resiquimod
- Podophyllotoxin
- Docosanol
- Tromantadine
- Inosine
- Lysozyme
- Ibacitabine
- Lysine
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Other
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- Ingenol mebutate
- Metronidazole
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Antibacterials: protein synthesis inhibitors (J01A, J01B, J01F, J01G, QJ01XQ)
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| 30S |
Aminoglycosides
(initiation inhibitors) |
| -mycin (Streptomyces) |
- Streptomycin#
- Dihydrostreptomycin
- Neomycin#
- Framycetin
- Paromomycin
- Ribostamycin
- Kanamycin#
- Amikacin
- Arbekacin
- Bekanamycin
- Dibekacin
- Tobramycin
- Spectinomycin#
- Hygromycin B
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| -micin (Micromonospora) |
- Gentamicin#
- Netilmicin
- Sisomicin
- Isepamicin
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Tetracycline antibiotics
(tRNA binding) |
| Tetracyclines |
- Doxycycline#
- Chlortetracycline
- Clomocycline
- Demeclocycline
- Lymecycline
- Meclocycline
- Metacycline
- Minocycline
- Oxytetracycline
- Penimepicycline
- Rolitetracycline
- Tetracycline
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| Glycylcyclines |
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| 50S |
Oxazolidinone
(initiation inhibitors) |
- Eperezolid
- Linezolid
- Posizolid
- Radezolid
- Ranbezolid
- Sutezolid
- Tedizolid
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| Peptidyl transferase |
| Amphenicols |
- Chloramphenicol#
- Azidamfenicol
- Thiamphenicol
- Florfenicol
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| Pleuromutilins |
- Retapamulin
- Tiamulin
- Valnemulin
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| MLS (transpeptidation/translocation) |
| Macrolides |
- Azithromycin#
- Clarithromycin
- Dirithromycin
- Erythromycin#
- Flurithromycin
- Josamycin
- Midecamycin
- Miocamycin
- Oleandomycin
- Rokitamycin
- Roxithromycin
- Spiramycin
- Troleandomycin
- Tylosin
- Ketolides
- Telithromycin
- Cethromycin
- Solithromycin†
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| Lincosamides |
- Clindamycin#
- Lincomycin
- Pirlimycin
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| Streptogramins |
- Pristinamycin
- Quinupristin/dalfopristin
- Virginiamycin
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| EF-G |
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- #WHO-EM
- ‡Withdrawn from market
- Clinical trials:
- †Phase III
- §Never to phase III
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Antihypertensives: diuretics (C03)
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Sulfonamides
(and etacrynic acid) |
| CA inhibitors (at PT) |
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| Loop (Na-K-Cl at AL) |
- Furosemide#
- Bumetanide
- Etacrynic acid
- Etozoline
- Muzolimine
- Piretanide
- Tienilic acid
- Torasemide
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Thiazides (Na-Cl at DCT,
Calcium-sparing) |
- Altizide
- Bendroflumethiazide
- Chlorothiazide
- Cyclopenthiazide
- Cyclothiazide
- Epitizide
- Hydrochlorothiazide#
- Hydroflumethiazide
- Mebutizide
- Methyclothiazide
- Polythiazide
- Trichlormethiazide
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| Thiazide-likes (primarily DCT) |
- Quinethazone
- Clopamide
- Chlortalidone
- Mefruside
- Clofenamide
- Metolazone
- Meticrane
- Xipamide
- Indapamide
- Clorexolone
- Fenquizone
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| Potassium-sparing (at CD) |
| ESC blockers |
- Amiloride#
- Triamterene
- Benzamil
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| Aldosterone antagonists |
- Spirolactones: Spironolactone#
- Eplerenone
- Potassium canrenoate
- Canrenone
- Non-steroidal: Finerenone
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| Osmotic diuretics (PT, DL) |
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Vasopressin receptor inhibitors
(DCT and CD) |
- Vaptans: Conivaptan
- Mozavaptan
- Satavaptan
- Tolvaptan
- Others: Demeclocycline
- Lithium carbonate
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| Other |
- Ethanol, Isopropanol, 2M2B
- mercurial diuretics (Chlormerodrin, Mersalyl, Meralluride)
- Theobromine
- Cicletanine
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- #WHO-EM
- ‡Withdrawn from market
- Clinical trials:
- †Phase III
- §Never to phase III
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