Chemistry:Demeclocycline

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Short description: Chemical compound

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Demeclocycline
File:Frameless
demeclocycline 3D BS
Clinical data
Trade namesDeclomycin
Other namesRP-10192, demethylchlortetracycline
AHFS/Drugs.comMonograph
MedlinePlusa682103
Pregnancy
category
  • US: D (Evidence of risk)
Routes of
administration		Oral
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Bioavailability60–80%
Protein binding41–50%
MetabolismHepatic
Elimination half-life10–17 hours
ExcretionRenal
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
Chemical and physical data
FormulaC21H21ClN2O8
Molar mass464.86 g·mol−1
3D model (JSmol)
  (verify)

Demeclocycline (INN, BAN, USAN, brand name Declomycin) is a tetracycline antibiotic which was derived from a mutant strain of Streptomyces aureofaciens.[1][2]

Uses

Demeclocycline is officially indicated for the treatment of various types of bacterial infections.[3] It is used as an antibiotic in the treatment of Lyme disease,[4] acne,[5] and bronchitis.[6] Resistance, though, is gradually becoming more common,[7] and demeclocycline is now rarely used for treatment of infections.[8][9]

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.[10] Physiologically, this works by reducing the responsiveness of the collecting tubule cells to ADH.[11]

The use in SIADH actually relies on a side effect; demeclocycline induces nephrogenic diabetes insipidus (dehydration due to the inability to concentrate urine).[10][12][13]

The use of demeclocycline in SIADH was first reported in 1975,[14] 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treatment at the time.[15] Demeclocycline used to be the drug of choice for treating SIADH.[13] Meanwhile, it might be superseded, now that vasopressin receptor antagonists, such as tolvaptan, became available.[15]

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.[9]

Side effects and interactions

The side effects are similar to those of other tetracyclines. Skin reactions with sunlight have been reported.[15] Like only few other known tetracycline derivatives, demeclocycline causes nephrogenic diabetes insipidus.[16] Furthermore, demeclocycline might have psychotropic side effects similar to lithium.[17]

Tetracyclines bind to cations, 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.[9]

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).[1][7]

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.[18][19][20] Exactly how demeclocycline does this has yet to be elucidated, however.[20]

Brand names

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

References

  1. ↑ 1.0 1.1 "Tetracyclines, molecular and clinical aspects". The Journal of Antimicrobial Chemotherapy 29 (3): 245–277. March 1992. doi:10.1093/jac/29.3.245. PMID 1592696. 
  2. ↑ The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. 14 November 2014. pp. 356–. ISBN 978-1-4757-2085-3. https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA356. 
  3. ↑ "Demeclocycline Hydrochloride - demeclocycline tablet". DailyMed. U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=4ff23e3b-e111-47fd-9776-1d89d6da049b. 
  4. ↑ "The Antibiotic Rotational Protocol". The Top 10 Lyme Disease Treatments: Defeat Lyme Disease with the Best of Conventional and Alternative Medicine. BioMed Publishing. 2007. pp. 84, 86. ISBN 9780976379713. https://books.google.com/books?id=J4TFtQeHkQAC&pg=PA84. 
  5. ↑ "Ad Hoc Committee report: systemic antibiotics for treatment of acne vulgaris: efficacy and safety". Archives of Dermatology 111 (12): 1630–1636. December 1975. doi:10.1001/archderm.1975.01630240086015. PMID 128326. 
  6. ↑ "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 13 (4): 197–202. 1985. doi:10.1177/030006058501300401. PMID 3930309. 
  7. ↑ 7.0 7.1 "Tetracyclines: antibiotic action, uptake, and resistance mechanisms". Archives of Microbiology 165 (6): 359–369. June 1996. doi:10.1007/s002030050339. PMID 8661929. 
  8. ↑ "Tetracyclines". The Medical Clinics of North America 79 (4): 789–801. July 1995. doi:10.1016/S0025-7125(16)30039-6. PMID 7791423. 
  9. ↑ 9.0 9.1 9.2 Lexi-Comp (August 2008). "Demeclocycline". The Merck Manual Professional. http://www.merck.com/mmpe/lexicomp/demeclocycline.html.  Retrieved on October 27, 2008.
  10. ↑ 10.0 10.1 "Management of hyponatremia". American Family Physician 69 (10): 2387–2394. May 2004. PMID 15168958. http://www.aafp.org/afp/20040515/2387.html. Retrieved 2008-10-28. 
  11. ↑ "Demeclocycline attenuates hyponatremia by reducing aquaporin-2 expression in the renal inner medulla". American Journal of Physiology. Renal Physiology 305 (12): F1705–F1718. December 2013. doi:10.1152/ajprenal.00723.2012. PMID 24154696. 
  12. ↑ "Demeclocycline-induced diabetes insipidus". JAMA 229 (6): 676–677. August 1974. doi:10.1001/jama.1974.03230440034026. PMID 4277429. 
  13. ↑ 13.0 13.1 "Evidence for the use of demeclocycline in the treatment of hyponatraemia secondary to SIADH: a systematic review". International Journal of Clinical Practice 69 (12): 1396–1417. December 2015. doi:10.1111/ijcp.12713. PMID 26289137. 
  14. ↑ "Demeclocycline treatment in the syndrome of inappropriate antidiuretic hormone secretion". Annals of Internal Medicine 83 (5): 654–656. November 1975. doi:10.7326/0003-4819-83-5-654. PMID 173218. 
  15. ↑ 15.0 15.1 15.2 "A brief review of drug-induced syndrome of inappropriate secretion of antidiuretic hormone". Medscape Pharmacotherapy 4 (1). 2002. http://www.medscape.com/viewarticle/420687_print. 
  16. ↑ "Tetracycline Nephrotoxicity". Nephrotoxic Mechanisms of Drugs and Environmental Toxins. Boston, MA: Springer. 1982. pp. 165–177. doi:10.1007/978-1-4684-4214-4_15. ISBN 978-1-4684-4216-8. https://books.google.com/books?id=EKPqBwAAQBAJ&pg=PA165. 
  17. ↑ "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 19 (1): 157–169. January 1995. doi:10.1016/0278-5846(94)00112-U. PMID 7708928. 
  18. ↑ "Disorders of water metabolism". Clinical Neuroendocrinology. Handbook of Clinical Neurology. 124. Elsevier Science. 2014. pp. 37–52 (43). doi:10.1016/B978-0-444-59602-4.00003-4. ISBN 978-0-444-62612-7. https://books.google.com/books?id=qH9zAwAAQBAJ&pg=PA43. 
  19. ↑ Vasopressin: Disturbed Secretion and Its Effects. Springer Science & Business Media. 6 December 2012. pp. 180–. ISBN 978-94-009-0449-1. https://books.google.com/books?id=UQztCAAAQBAJ&pg=PA180. 
  20. ↑ 20.0 20.1 Textbook of Nephro-Endocrinology. Academic Press. 12 January 2009. pp. 251–. ISBN 978-0-08-092046-7. https://books.google.com/books?id=TsbV_KMn4yAC&pg=PA251. 



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