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 category	US: D (Evidence of risk)
Legal status	℞ (Prescription only)
Routes of administration	Oral
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 Template:CAS (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
Molecular mass	464.853 g/mol
SMILES 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
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 (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.

Uses

It is officially indicated for the treatment of various types of bacterial infections. It is used as an antibiotic in the treatment of Lyme disease, acne, and bronchitis. 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. 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). The use of demeclocycline in SIADH was first reported in 1975, 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. 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.

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.

Side effects and interactions

These are similar to those of other tetracyclines. Skin reactions with sunlight have been reported. 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.

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. Exactly how demeclocycline does this has yet to be elucidated, however.