Methdilazine Hydrochloride

Methdilazine hydrochloride is an orally active antibiotic (histamine antagonist). Methdilazine hydrochloride can inhibit various mycobacterium with MIC values at 5-15 μg/mL in vitro and in vivo, which can be used for the research of infectious diseases[1][2].

Signaling Pathways >> Immunology/Inflammation >> Histamine Receptor

Research Areas >> Infection

Signaling Pathways >> Anti-infection >> Bacterial

Signaling Pathways >> GPCR/G Protein >> Histamine Receptor

Methdilazine hydrochloride (0-20 μg/mL approximately, 18 h) inhibits kinds of mycobacterium with MIC values ranging from 5 μg/mL to 15 μg/mL[1]. Cell Proliferation Assay[1] Cell Line: M. smegmatis 798/1546, M.,fortuitum 1529, M. scrofulaceum 1323, M. gordonae 1324, M. rnarinum 50, M.,flavescens 1541, M. terrae 1450, M. tuberculosis, H37Ra 16, H37Rv 16, K1, K2, ICRC bacillus,'Skinsnes' bacillus. Concentration: 0-20 μg/mL approximately Incubation Time: 18 h Result: Inhibited mycobacterium with MIC values ranging from 5 μg/mL to 15 μg/mL.

Methdilazine hydrochloride (Intraperitoneal injection, 10 μg/gm body wt/day, 6 weeks) is antagonistic to mycobacteria in H37Rv infected mice[1]. Methdilazine hydrochloride (Oral administration, 10 mg/kg per day, 28 days) improves survival of Mycobacterium Tuberculosis (Mtb) H37Rv infected mice[2]. Animal Model: H37Rv infected mice[1] Dosage: 10 μg/gm body wt/day, 6 weeks Administration: Intraperitoneal injection Result: Displayed an anti-mycobacterial activity to mycobacteria. Animal Model: Mycobacterium Tuberculosis (Mtb) H37Rv infected Swiss albino male mice[2] Dosage: 10 mg/kg per day for 28 days Administration: Oral administration Result: Increased surviving time to 28 days with no sign of disease, showed 71.42% survival.

[1]. A N Chakrabarty, et al. Antimycobacterial activity of methdilazine (Md), an antimicrobic phenothiazine. APMIS. 1993 Jun;101(6):449-54.

[2]. Noton K Dutta, et al. Activity of the phenothiazine methdilazine alone or in combination with isoniazid or streptomycin against Mycobacterium tuberculosis in mice. J Med Microbiol. 2009 Dec;58(Pt 12):1667-1668.

MOLECULAR FORMULA :

C18-H20-N2-S.Cl-H

MOLECULAR WEIGHT :

332.92

WISWESSER LINE NOTATION :

T C666 BN ISJ B1- CT5NTJ A1 &GH

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

260 mg/kg

TOXIC EFFECTS :

Behavioral - altered sleep time (including change in righting reflex) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - dyspnea

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

75 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 :

Intravenous

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

22 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 :

Oral

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

190 mg/kg

TOXIC EFFECTS :

Behavioral - altered sleep time (including change in righting reflex) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - dyspnea

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

100 mg/kg

TOXIC EFFECTS :

Behavioral - altered sleep time (including change in righting reflex) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - dyspnea

TYPE OF TEST :

LDLo - Lowest published lethal dose

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

25 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 :

Intramuscular

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

300 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 :

Intravenous

SPECIES OBSERVED :

Mammal - dog

DOSE/DURATION :

25 mg/kg

TOXIC EFFECTS :

Behavioral - altered sleep time (including change in righting reflex) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - dyspnea

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intravenous

SPECIES OBSERVED :

Rodent - rabbit

DOSE/DURATION :

17 mg/kg

TOXIC EFFECTS :

Behavioral - altered sleep time (including change in righting reflex) Behavioral - convulsions or effect on seizure threshold Lungs, Thorax, or Respiration - dyspnea

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Oral

SPECIES OBSERVED :

Rodent - guinea pig

DOSE/DURATION :

263 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 :

Oral

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

9880 mg/kg/52W-I

TOXIC EFFECTS :

Related to Chronic Data - death

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

150 mg/kg

SEX/DURATION :

female 2-4 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - pre-implantation mortality (e.g. reduction in number of implants per female; total number of implants per corpora lutea)

MUTATION DATA

TYPE OF TEST :

Morphological transformation

TEST SYSTEM :

Rodent - hamster Embryo

DOSE/DURATION :

10 mg/L

REFERENCE :

ENMUDM Environmental Mutagenesis. (New York, NY) V.1-9, 1979-87. For publisher information, see EMMUEG. Volume(issue)/page/year: 8(Suppl 6),4,1986