Demeclocycline

Demeclocycline is an orally active tetracycline antibiotic. Demeclocycline impairs protein synthesis by binding to the 30S ribosomal subunit to inhibit binding of aminoacyl tRNA. Demeclocycline shows anti-bacterial activitise to a wide variety of bacterial infections[1][2].

Research Areas >> Cancer

Research Areas >> Infection

Research Areas >> Inflammation/Immunology

Signaling Pathways >> Anti-infection >> Bacterial

Demeclocycline (0-100 μM; 24 h) treatment reduces AQP2 abundance in mpkCCD cells[3]. Demeclocycline (10 μM; 24 h) treatment promotes the activity of monocytes and macrophages[4]. Demeclocycline (1-10 μM; 72 h) treatment directly affects the growth of brain tumorinitiating cells[4]. Western Blot Analysis[3] Cell Line: MpkCCD cells Concentration: 0-100 μM Incubation Time: 24 hours Result: Decreased AQP2 abundance in mpkCCD cells, with significant effects at 50 μM. Cell Viability Assay[4] Cell Line: mouse bone marrow derived macrophages and monocytes Concentration: 10 μM Incubation Time: 24 hours Result: Enhanced TNF-α production and modulated monocyte functions. Cell Viability Assay[4] Cell Line: brain tumorinitiating cells Concentration: 1, 5, and 10 μM Incubation Time: 72 hours Result: Inhibited cells growth in two ways: using monocytes as an intermediary, and directly by affecting the proliferation and sphere-forming capacity of brain tumorinitiating cells.

Demeclocycline (Intraperitoneal injection; 40 mg/kg; once daily; 48 h) treatment results in a significant reduction of hyponatremia and a significant correction of the hypoosmolality, and is not nephrotoxic[3]. Animal Model: Male Wistar rats induced with hyponatremia[3] Dosage: 40 mg/kg Administration: Intraperitoneal injection; 40 mg/kg; once daily; 48 hours Result: Increased urine volume, decreased urine osmolality, and caused a significantly increased fractional excretion of water. Animal Model: Male Wistar rats induced with hyponatremia[3] Dosage: 40 mg/kg Administration: Intraperitoneal injection; 40 mg/kg; once daily; 48 hours Result: Indicated the effect in the renal inner medulla for AQP2 and AC5/6 specifically, and not secondary toxicity effect.

[1]. I Chopra, et al. Tetracyclines, molecular and clinical aspects. J Antimicrob Chemother. 1992 Mar;29(3):245-77.

[2]. D Schnappinger, et al. Tetracyclines: antibiotic action, uptake, and resistance mechanisms. Arch Microbiol. 1996 Jun;165(6):359-69.

[3]. Marleen L A Kortenoeven, et al. Demeclocycline attenuates hyponatremia by reducing aquaporin-2 expression in the renal inner medulla. Am J Physiol Renal Physiol. 2013 Dec 15;305(12):F1705-18.

[4]. Susobhan Sarkar, et al. Demeclocycline Reduces the Growth of Human Brain Tumor-Initiating Cells: Direct Activity and Through Monocytes. Front Immunol. 2020 Feb 21;11:272.

MOLECULAR FORMULA :

C21-H21-Cl-N2-O8

MOLECULAR WEIGHT :

464.89

WISWESSER LINE NOTATION :

L E6 C666 BV FV CU GUTTT&J DQ EQ GVZ HQ IN1&1 MQ OG RQ

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human

DOSE/DURATION :

420 mg/kg/6W

TOXIC EFFECTS :

Endocrine - diabetes insipidus (nephrogenic or CNS) Biochemical - Metabolism (Intermediary) - effect on cyclic nucleotides

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human

DOSE/DURATION :

10 mg/kg

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Human

DOSE/DURATION :

68 mg/kg/8D

TOXIC EFFECTS :

Kidney, Ureter, Bladder - urine volume increased Kidney, Ureter, Bladder - other changes in urine composition

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

>6750 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

358 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

>2 gm/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

4 gm/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

454 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

2500 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

79 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Unreported

DOSE :

240 mg/kg

SEX/DURATION :

female 1-39 week(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - other postnatal measures or effects

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

5 gm/kg

SEX/DURATION :

female 1-22 day(s) after conception lactating female 21 day(s) post-birth

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue) Reproductive - Specific Developmental Abnormalities - skin and skin appendages Reproductive - Effects on Newborn - weaning or lactation index (e.g., # alive at weaning per # alive at day 4)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

5 gm/kg

SEX/DURATION :

female 1-22 day(s) after conception lactating female 21 day(s) post-birth

TOXIC EFFECTS :

Reproductive - Effects on Newborn - other postnatal measures or effects

MUTATION DATA

TYPE OF TEST :

DNA inhibition

TEST SYSTEM :

Human Lymphocyte

DOSE/DURATION :

3750 ug/L

REFERENCE :

BCPHBM British Journal of Clinical Pharmacology. (Blackwell Scientific Pub. Ltd., POB 88, Oxford, UK) V.1- 1974- Volume(issue)/page/year: 16,127,1983 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X5539 No. of Facilities: 10 (estimated) No. of Industries: 1 No. of Occupations: 1 No. of Employees: 330 (estimated) No. of Female Employees: 120 (estimated)