Methotrexate disodium

Methotrexate (Amethopterin) disodium, an antimetabolite and antifolate agent, inhibits the enzyme dihydrofolate reductase, thereby preventing the conversion of folic acid into tetrahydrofolate, and inhibiting DNA synthesis. Methotrexate disodium, also an immunosuppressant and antineoplastic agent, is used for the research of rheumatoid arthritis and a number of different cancers (such as acute lymphoblastic leukemia)[1][2][3].

Signaling Pathways >> Apoptosis >> Apoptosis

Research Areas >> Cancer

Signaling Pathways >> Cell Cycle/DNA Damage >> Antifolate

Signaling Pathways >> Cell Cycle/DNA Damage >> DNA/RNA Synthesis

Signaling Pathways >> Antibody-drug Conjugate >> ADC Cytotoxin

Research Areas >> Inflammation/Immunology

Traditional Cytotoxic Agents

Methotrexate (Amethopterin) disodium reduces thymus and spleen indices of mice. Methotrexate disodium markedly decreases white blood cells, thymic and splenic lymphocytes at dose ≥5 mg/kg. However, there is a significant difference between the treatment plus control group and the model group (p<0.01). The combination of grape seed proanthocyanidins and Siberian ginseng eleutherosides obviously diminishes the effects of Methotrexate exposure on indices of thymus and spleens in mice[2]. Methotrexate (MTX) disodium (2 mg/kg; i.p.; once in a week for 5 weeks) is effective in Freund's complete adjuvant-induced arthritis. The combination of Methotrexate disodium (1 mg/kg; i.p.; once in a week for 5 weeks) and Curcumin (30 mg/kg and 100 mg/kg, thrice a week for 5 weeks; i.p.) shows a significant anti-arthritic action and protection from hematological toxicity[4].

[1]. Tian H, et al. Understanding the mechanisms of action of methotrexate: implications for the treatment of rheumatoid arthritis. Bull NYU Hosp Jt Dis. 2007;65(3):168-73.

[2]. Swierkot J, et al. Methotrexate in rheumatoid arthritis. Pharmacol Rep. 2006 Jul-Aug;58(4):473-92.

[3]. Swierkot J, et al. Methotrexate in rheumatoid arthritis. Pharmacol Rep. 2006 Jul-Aug;58(4):473-92.

[4]. Banji D, et al. Evaluation of the concomitant use of methotrexate and curcumin on Freund's complete adjuvant-induced arthritis and hematological indices in rats. Indian J Pharmacol. 2011;43(5):546-550.

MOLECULAR FORMULA :

C20-H20-N8-O5.2Na

MOLECULAR WEIGHT :

498.46

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

284 mg/kg

TOXIC EFFECTS :

Details of toxic effects not reported other than lethal dose value

REFERENCE :

JNCIAM Journal of the National Cancer Institute. (Washington, DC) V.1-60, 1940-78. For publisher information, see JJIND8. Volume(issue)/page/year: 58,735,1977 ** REPRODUCTIVE DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

120 mg/kg

SEX/DURATION :

male 60 day(s) pre-mating

TOXIC EFFECTS :

Reproductive - Paternal Effects - testes, epididymis, sperm duct Reproductive - Fertility - male fertility index (e.g. # males impregnating females per # males exposed to fertile nonpregnant females)

REFERENCE :

JNCIAM Journal of the National Cancer Institute. (Washington, DC) V.1-60, 1940-78. For publisher information, see JJIND8. Volume(issue)/page/year: 58,735,1977 *** NIOSH STANDARDS DEVELOPMENT AND SURVEILLANCE DATA *** NIOSH OCCUPATIONAL EXPOSURE SURVEY DATA : NOES - National Occupational Exposure Survey (1983) NOES Hazard Code - X5643 No. of Facilities: 4 (estimated) No. of Industries: 1 No. of Occupations: 15 No. of Employees: 1233 (estimated)