Metoprine

Metoprine (BW 197U) is a potent histamine N-methyltransferase (HMT) inhibitor. Metoprine, a diaminopyrimidine derivative, can cross the blood-brain barrier and increase brain histamine levels by inhibiting HMT[1][2]. Metoprine is an antifolate and antitumor agent[3].

Research Areas >> Cancer

Signaling Pathways >> Epigenetics >> Histone Methyltransferase

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

Research Areas >> Neurological Disease

Metoprine (BW 197U; 2-10 mg/kg; IP) ameliorates the memory deficits induced by nucleus basalis magnocellularis (NBM) lesions in a dose-dependent manner[2]. Intraperitoneal administration of Metoprine produces various behavioral effects, including decreases in food intake and increases in water consumption[1]. Animal Model: Male Sprague-dawley rats (200-280g)[2] Dosage: 2, 5, 10 mg/kg Administration: IP Result: Ameliorated the memory deficits induced by nucleus basalis magnocellularis (NBM) lesions in a dose-dependent manner and significanty prolonged transfer latency at a high dose of 10 mg/kg.

[1]. Junichi Kitanaka, et al. Brain Histamine N-Methyltransferase As a Possible Target of Treatment for Methamphetamine Overdose. Drug Target Insights. 2016 Mar 2;10:1-7.

[2]. Zhong Chen, et al. Effects of brain histamine on memory deficit induced by nucleus basalis-lesion in rats. Acta Pharmacol Sin. 2002 Jan;23(1):66-70.

[3]. John R Horton, et al. Structural basis for inhibition of histamine N-methyltransferase by diverse drugs. J Mol Biol. 2005 Oct 21;353(2):334-344.

DATA ITEMS CITED :

7

MOLECULAR FORMULA :

C11-H10-Cl2-N4

MOLECULAR WEIGHT :

269.15

WISWESSER LINE NOTATION :

T6N CNJ BZ DZ ER CG DG& F1

HEALTH HAZARD DATA

ACUTE TOXICITY DATA

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - rat

DOSE/DURATION :

7 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 - mouse

DOSE/DURATION :

50 mg/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Tumorigenic - active as anti-cancer agent

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

40 mg/kg/21D-I

TOXIC EFFECTS :

Related to Chronic Data - death

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

2500 ug/kg

SEX/DURATION :

female 7 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus) Reproductive - Effects on Embryo or Fetus - fetal death

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

5 mg/kg

SEX/DURATION :

female 8-9 day(s) after conception

TOXIC EFFECTS :

Reproductive - Fertility - post-implantation mortality (e.g. dead and/or resorbed implants per total number of implants)

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Oral

DOSE :

7500 ug/kg

SEX/DURATION :

female 6-8 day(s) after conception

TOXIC EFFECTS :

Reproductive - Specific Developmental Abnormalities - craniofacial (including nose and tongue)

MUTATION DATA

TEST SYSTEM :

Human

DOSE/DURATION :

2800 ug/kg

REFERENCE :

RBBIAL Revista Brasileira de Biologia. Brazilian Review of Biology. (Academia Brasileira de Ciencias, Caixa Postal 229, ZC-00 Rio de Janeiro, Brazil) V.1- 1941- Volume(issue)/page/year: 25,145,1965