Demeclocycline hydrochloride

Demeclocycline hydrochloride (CAS No. 64-73-3) is a semisynthetic tetracycline compound, whose core targets include bacterial ribosomes (exerting antibacterial effects by inhibiting protein synthesis) and arginine vasopressin (ADH) receptors (blocking ADH-mediated water reabsorption); it can also regulate the expression of genes such as DDIT4 and FZD5 in brain tumor-initiating cells (BTICs) and activate monocytes. It is effective against most Gram-negative bacteria with an antibacterial spectrum similar to that of tetracycline. The concentrations commonly used in laboratory assays range from 1 to 10 μM (1, 5, and 10 μM for BTIC growth inhibition assays, and 10 μM for monocyte activation assays). Clinically effective therapeutic concentrations are achieved with the following oral dosages: 600–1200 mg per day for adults (administered in 2–4 divided doses), adjusted to 250 mg once or twice daily for patients with renal impairment; the drug concentration in breast milk ranges from 50 mcg/L to 1 mg/L, with acceptable safety for short-term use during lactation. Its biological activities are manifested as broad-spectrum antibacterial effects, induction of nephrogenic diabetes insipidus for the treatment of syndrome of inappropriate antidiuretic hormone secretion (SIADH)-associated hyponatremia, and inhibition of BTIC growth either directly or via monocyte activation. It has a serum protein binding rate of approximately 70%, is mainly eliminated via the renal pathway, and has an elimination half-life of about 1 hour. Common adverse reactions include gastrointestinal discomfort and nephrotoxicity, necessitating monitoring of liver and renal functions during long-term administration.

References:

[1] Miell J, Dhanjal P, Jamookeeah C. Evidence for the use of demeclocycline in the treatment of hyponatraemia secondary to SIADH: a systematic review. Int J Clin Pract. 2015 Dec;69(12):1396-417. doi: 10.1111/ijcp.12713. Epub 2015 Aug 19. PMID: 26289137; PMCID: PMC5042094.

[2] Sarkar S, Li Y, Mirzaei R, Rawji KS, Poon CC, Wang J, Kumar M, Bose P, Yong VW. Demeclocycline Reduces the Growth of Human Brain Tumor-Initiating Cells: Direct Activity and Through Monocytes. Front Immunol. 2020 Feb 21;11:272. doi: 10.3389/fimmu.2020.00272. PMID: 32153581; PMCID: PMC7047330.

[3] LiverTox: Clinical and Research Information on Drug Induced Liver Injury [Internet]. Bethesda (MD): National Institute of Diabetes and Digestive and Kidney Diseases; 2012-. Demeclocycline.

[4] Drugs and Lactation Database (LactMed®) [Internet]. Bethesda (MD): National Institute of Child Health and Human Development; 2006-. Demeclocycline.