Demeclocycline

Demeclocycline

Systematic (IUPAC) name
(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
Clinical data
Trade names	Declomycin
AHFS/Drugs.com	monograph
MedlinePlus	a682103
Pregnancy cat.	D(US)
Legal status	℞ Prescription only
Routes	Oral
Pharmacokinetic data
Bioavailability	60–80%
Protein binding	41–50%
Metabolism	Hepatic
Half-life	10–17 hours
Excretion	Renal
Identifiers
CAS number	127-33-3 Y 64-73-3 (HCl)
ATC code	D06AA01 J01AA01
PubChem	CID 5311063
DrugBank	APRD00272
ChemSpider	10482117 Y
UNII	5R5W9ICI6O Y
KEGG	D03680 Y
ChEBI	CHEBI:4392 Y
ChEMBL	CHEMBL1591 Y
Chemical data
Formula	C21H21ClN2O8
Mol. mass	464.853 g/mol
SMILES	eMolecules & PubChem
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 Y Key:FMTDIUIBLCQGJB-SEYHBJAFSA-N Y
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Demeclocycline (marketed as Declomycin, Declostatin and Ledermycin) is a tetracycline antibiotic.

It is derived from a strain of Streptomyces aureofaciens.^[1]

Uses

In infections

It is officially indicated for the treatment of various types of bacterial infections.^[2]

Its use as an antibiotic is particularly in Lyme disease, acne and bronchitis.^{[citation needed]}

Resistance is gradually becoming more common, and demeclocycline is now rarely used for infections.

In SIADH

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.^[3]

The use in SIADH actually relies on a side effect; demeclocycline induces nephrogenic diabetes insipidus (dehydration due to the inability to concentrate urine).^[3] The use of demeclocycline in SIADH was first reported in 1975,^[4] 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treatment at the time.^[5] Demeclocycline has since been the drug of choice for treating SIADH, although it may be superseded as vasopressin receptor antagonists, such as tolvaptan, become available.^[5]

Contraindications

As 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.^[6]

Side effects and interactions

These are similar to those of other tetracyclines. Skin reactions with sunlight have been reported.^[5] 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 GI tract. Demeclocycline should not be taken with food (particularly milk and other dairy products) or antacids.^[6]

Mechanism of action

As with related tetracycline antibiotics, demeclocycline acts by binding to the 30S- and 50S-RNA, which impairs protein synthesis by bacteria. It is bacteriostatic (it impairs bacterial growth but does not kill bacteria directly).

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.^[7]

References

1. ^ "demeclocycline" at Dorland's Medical Dictionary
2. ^ "DailyMed: About DailyMed". http://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?id=673. Retrieved 2008-12-20. 
3. ^ ^{a b} Goh KP (May 2004). "Management of hyponatremia". American Family Physician 69 (10): 2387–94. PMID 15168958. http://www.aafp.org/afp/20040515/2387.html. 
4. ^ 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. PMID 173218. 
5. ^ ^{a b c} Tolstoi LG (2002). "A brief review of drug-induced syndrome of inappropriate secretion of antidiuretic hormone". Medscape Pharmacotherapy 4 (1). http://www.medscape.com/viewarticle/420687_print.  Retrieved on October 27, 2008.
6. ^ ^{a b} Lexi-Comp (August 2008). "Demeclocycline". The Merck Manual Professional. http://www.merck.com/mmpe/lexicomp/demeclocycline.html.  Retrieved on October 27, 2008.
7. ^ De Troyer A, Demanet JC (1975). "Correction of antidiuresis by demeclocycline". N Engl J Med 293 (18): 915–8. doi:10.1056/NEJM197510302931809. PMID 170519.