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Demeclocycline

Chemical compound


Chemical compound

FieldValue
verifiedrevid460775334
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
imageDemeclocycline.svg
image_classskin-invert-image
image2Demeclocycline 3D.png
image_class2bg-transparent
tradenameDeclomycin
Drugs.com
MedlinePlusa682103
pregnancy_USD
legal_statusRx-only
routes_of_administrationOral
bioavailability60–80%
protein_bound41–50%
metabolismHepatic
elimination_half-life10–17 hours
excretionRenal
CAS_number_Ref
CAS_number127-33-3
CAS_supplemental
(HCl)
ATC_prefixD06
ATC_suffixAA01
ATC_supplemental
PubChem54680690
DrugBank_Ref
DrugBankDB00618
ChemSpiderID_Ref
ChemSpiderID10482117
UNII_Ref
UNII5R5W9ICI6O
KEGG_Ref
KEGGD03680
ChEBI_Ref
ChEBI4392
ChEMBL_Ref
ChEMBL1591
synonymsRP-10192, demethylchlortetracycline
C21H=21Cl=1N=2O=8
smilesNC(=O)C1C(=O)[C@@]2(O)C(O)=C3C(=O)c4c(O)ccc(Cl)c4C@@H[C@H]3C[C@H]2C(C=1O)N(C)C
StdInChI_Ref
StdInChI1S/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
StdInChIKey_Ref
StdInChIKeyFMTDIUIBLCQGJB-SEYHBJAFSA-N

| Drugs.com =

| elimination_half-life = 10–17 hours

(HCl)

Demeclocycline (INN, BAN, USAN, brand name Declomycin) is a tetracycline antibiotic which was derived from a mutant strain of Streptomyces aureofaciens.

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.

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 (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 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

The side effects are similar to those of other tetracyclines. Skin reactions with sunlight have been reported. Furthermore, demeclocycline might have psychotropic side effects similar to lithium.

Tetracyclines bind to cations, such as calcium, iron (when given orally), and magnesium, rendering them insoluble and nonadsorbable 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.

Brand names

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

References

References

  1. (March 1992). "Tetracyclines, molecular and clinical aspects". The Journal of Antimicrobial Chemotherapy.
  2. (14 November 2014). "The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies". Springer.
  3. "Demeclocycline Hydrochloride - demeclocycline tablet". U.S. National Library of Medicine.
  4. (2007). "The Top 10 Lyme Disease Treatments: Defeat Lyme Disease with the Best of Conventional and Alternative Medicine". BioMed Publishing.
  5. (December 1975). "Ad Hoc Committee report: systemic antibiotics for treatment of acne vulgaris: efficacy and safety". Archives of Dermatology.
  6. (1985). "A clinical comparison of pivmecillinam plus pivampicillin (Miraxid) and a triple tetracycline combination (Deteclo) in respiratory infections treated in general practice". The Journal of International Medical Research.
  7. (June 1996). "Tetracyclines: antibiotic action, uptake, and resistance mechanisms". Archives of Microbiology.
  8. (July 1995). "Tetracyclines". The Medical Clinics of North America.
  9. Lexi-Comp. (August 2008). "Demeclocycline".
  10. (May 2004). "Management of hyponatremia". American Family Physician.
  11. (December 2013). "Demeclocycline attenuates hyponatremia by reducing aquaporin-2 expression in the renal inner medulla". American Journal of Physiology. Renal Physiology.
  12. (August 1974). "Demeclocycline-induced diabetes insipidus". JAMA.
  13. (December 2015). "Evidence for the use of demeclocycline in the treatment of hyponatraemia secondary to SIADH: a systematic review". International Journal of Clinical Practice.
  14. (November 1975). "Demeclocycline treatment in the syndrome of inappropriate antidiuretic hormone secretion". Annals of Internal Medicine.
  15. (2002). "A brief review of drug-induced syndrome of inappropriate secretion of antidiuretic hormone". [[Medscape.
  16. (1982). "Nephrotoxic Mechanisms of Drugs and Environmental Toxins". Springer.
  17. (January 1995). "A comparative study on the effects of tetracyclines and lithium on the cyclic AMP second messenger system in rat brain". Progress in Neuro-Psychopharmacology & Biological Psychiatry.
  18. (2014). "Clinical Neuroendocrinology". Elsevier Science.
  19. (6 December 2012). "Vasopressin: Disturbed Secretion and Its Effects". Springer Science & Business Media.
  20. (12 January 2009). "Textbook of Nephro-Endocrinology". Academic Press.
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