Demeclocycline ( INN,

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, USAN, brand name Declomycin) is a tetracycline antibiotic which was derived from a mutant strain of ''

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''.

Uses

Demeclocycline 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 treatment of infections. Retrieved on October 27, 2008. It is widely used (though off-label in many countries including the United States) in the treatment of hyponatremia (low blood sodium concentration) due to the

syndrome of inappropriate antidiuretic hormone Syndrome of inappropriate antidiuretic hormone secretion (SIADH) is characterized by excessive unsuppressible release of antidiuretic hormone (ADH) either from the posterior pituitary gland, or an abnormal non-pituitary source. Unsuppressed ADH c ...

(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 Lithium carbonate is an inorganic compound, the lithium salt (chemistry), salt of carbonate with the chemical formula, formula . This white Salt (chemistry), salt is widely used in the processing of metal oxides. It is listed on the World Health O ...

, the only available treatment at the time. Demeclocycline used to be the drug of choice for treating SIADH. Meanwhile it might be superseded, now that vasopressin receptor antagonists, such as tolvaptan, became available.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. Like only few other known tetracycline derivatives, demeclocycline causes nephrogenic diabetes insipidus. Furthermore demeclocycline might have psychotropic side effects similar to lithium. Tetracyclines bind to

cation An ion () is an atom or molecule with a net electrical charge. The charge of an electron is considered to be negative by convention and this charge is equal and opposite to the charge of a proton, which is considered to be positive by convent ...

s, such as calcium, iron (when given orally), and magnesium, rendering them insoluble and inadsorbable 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

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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 The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; bloo ...

action of antidiuretic hormone by interfering with the intracellular

second messenger cascade Second messengers are intracellular signaling molecules released by the cell in response to exposure to extracellular signaling molecules—the first messengers. (Intercellular signals, a non-local form or cell signaling, encompassing both first ...

(specifically, inhibiting adenylyl cyclase activation) after the hormone binds to vasopressin V₂ receptors in the

kidney The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; bloo ...

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

Brand names

Brand names include Declomycin, Declostatin, Ledermycin, Bioterciclin, Deganol, Deteclo, Detravis, Meciclin, Mexocine, and Clortetrin.

References

{{Oxytocin and vasopressin receptor modulators Tetracycline antibiotics Chloroarenes Carboxamides Drugs with unknown mechanisms of action Triketones Nephrotoxins