Demeclocycline

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

Demeclocycline
Clinical data
Trade namesDeclomycin
Other namesRP-10192, demethylchlortetracycline
AHFS/Drugs.comMonograph
MedlinePlusa682103
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
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
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard100.004.396
Chemical and physical data
FormulaC21H21ClN2O8
Molar mass464.86 g·mol−1
3D model (JSmol)
SMILES
  • NC(=O)C1C(=O)[C@@]2(O)C(O)=C3C(=O)c4c(O)ccc(Cl)c4[C@@H](O)[C@H]3C[C@H]2C(C=1O)N(C)C
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
  (verify)

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treatment at the time.[15] Demeclocycline used to be the drug of choice for treating SIADH.[13] Meanwhile it might be superseded, now that vasopressin receptor antagonists, such as tolvaptan, became available.[15]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

These 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.

References
  1. Chopra, I.; Hawkey, P. M.; Hinton, M. (1992). "Tetracyclines, molecular and clinical aspects". J. Antimicrob. Chemother. 29 (3): 245–277. doi:10.1093/jac/29.3.245. PMID 1592696.
  2. J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 356–. ISBN 978-1-4757-2085-3.
  3. DailyMed. "Demeclocycline Hydrochloride - demeclocycline tablet". Drug label information. Retrieved 2008-12-20.
  4. Rosner, Bryan (2007). The Top 10 Lyme Disease Treatments: Defeat Lyme Disease with the Best of Conventional and Alternative Medicine. pp. 84, 86. ISBN 9780976379713.
  5. Ad Hoc Committee on the Use of Antibiotics in Dermatology (1975). "Systemic antibiotics for treatment of acne vulgaris: efficacy and safety". Arch. Dermatol. 111 (12): 1630–1636. doi:10.1001/archderm.1975.01630240086015. PMID 128326.
  6. Beatson, J. M.; Marsh, B. T.; Talbot, D. J. (1985). "A clinical comparison of pivmecillinam plus pivampicillin (Miraxid) and a triple tetracycline combination (Deteclo) in respiratory infections treated in general practice". J. Int. Med. Res. 13 (4): 197–202. doi:10.1177/030006058501300401. PMID 3930309. S2CID 23485353.
  7. Schnappinger, Dirk; Hillen, Wolfgang (July 1996). "Tetracyclines: Antibiotic action, uptake, and resistance mechanisms". Archives of Microbiology. 165 (6): 359–369. doi:10.1007/s002030050339. PMID 8661929. S2CID 6199423.
  8. Klein, Natalie C.; Cunha, Burke A. (1995). "Tetracyclines". Medical Clinics of North America. 79 (4): 789–801. doi:10.1016/S0025-7125(16)30039-6. PMID 7791423.
  9. Lexi-Comp (August 2008). "Demeclocycline". The Merck Manual Professional. Retrieved on October 27, 2008.
  10. Goh KP (May 2004). "Management of hyponatremia". American Family Physician. 69 (10): 2387–94. PMID 15168958. Archived from the original on 2008-10-16. Retrieved 2008-10-28.
  11. Kortenoeven, M. L.; Sinke, A. P.; Hadrup, N.; Trimpert, C.; Wetzels, J. F.; Fenton, R. A.; Deen, P. M. (2013). "Demeclocycline attenuates hyponatremia by reducing aquaporin-2 expression in the renal inner medulla". Am. J. Physiol. Renal Physiol. 305 (12): F1705–F1718. doi:10.1152/ajprenal.00723.2012. PMID 24154696. S2CID 17815411.
  12. Hayek, Alberto; Ramirez, Jimeno (1974). "Demeclocycline-induced diabetes insipidus". JAMA. 229 (6): 676–677. doi:10.1001/jama.1974.03230440034026. PMID 4277429.
  13. Miell, J.; Dhanjal, P.; Jamookeeah, C. (2015). "Evidence for the use of demeclocycline in the treatment of hyponatraemia secondary to SIADH: a systematic review". Int. J. Clin. Pract. 69 (12): 1396–1417. doi:10.1111/ijcp.12713. PMC 5042094. PMID 26289137.
  14. 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. doi:10.7326/0003-4819-83-5-654. PMID 173218.
  15. Tolstoi LG (2002). "A brief review of drug-induced syndrome of inappropriate secretion of antidiuretic hormone". Medscape Pharmacotherapy. 4 (1). Archived from the original on June 6, 2013.
  16. Cox, Malcolm (1982). "Tetracycline Nephrotoxicity". In Porter, George A. (ed.). Nephrotoxic Mechanisms of Drugs and Environmental Toxins. Boston, MA: Springer. pp. 165–177. doi:10.1007/978-1-4684-4214-4_15. ISBN 978-1-4684-4216-8.
  17. Mørk, A.; Geisler, A. (1995). "A comparative study on the effects of tetracyclines and lithium on the cyclic AMP second messenger system". Prog. Neuropsychopharmacol. Biol. Psychiatry. 19 (1): 157–169. doi:10.1016/0278-5846(94)00112-U. PMID 7708928. S2CID 36219362.
  18. Eric Fliers; Marta Korbonits; J.A. Romijn (28 August 2014). Clinical Neuroendocrinology. Elsevier Science. pp. 43–. ISBN 978-0-444-62612-7.
  19. L. Kovács; B. Lichardus (6 December 2012). Vasopressin: Disturbed Secretion and Its Effects. Springer Science & Business Media. pp. 180–. ISBN 978-94-009-0449-1.
  20. Ajay K. Singh; Gordon H. Williams (12 January 2009). Textbook of Nephro-Endocrinology. Academic Press. pp. 251–. ISBN 978-0-08-092046-7.
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