0MPTP hydrochloride

MPTP hydrochloride is a brain penetrant dopamine neurotoxin, inducing Parkinson’s Disease.

Signaling Pathways >> Others >> Others

Research Areas >> Neurological Disease

Pretreatment with 50 mM 4-phenylpyridine, reduces IC50 (concentration for 50% inhibition of twitch amplitude) values of MPTP from 53 to 18 mM and d-tubocurarine from 0.7 to 0.3 mM, respectively, in mouse phrenic nerve-diaphragm[3].

The toxic effect of MPTP can be completely abolished in vivo by treatment with a monoamine oxidase inhibitor and potentiated by an inhibitor of catechol-O-methyltransferase[1]. Allopurinol potentiated the MPTP (35 mg/kg)-induced decrease in the DOPAC+HVA/DA ratio and increase in striatal AA oxidation of the rat[2]. Gas1 expressions are significantly elevated in the majority of the reactive astrocytes of the brains with LPS or MPTP insults in animal models[4].

For the preparation of the LPS rat model and the MPTP mouse model, the treatments of the animals are performed. Briefly, adult rats receive unilateral injections of LPS (0.5 μL of 10 μg/μL diluted in 0.9% saline) into the medial forebrain bundle (MFB) at the following coordinates, AP-4.2 mm, L 1.5 mm, and V 7.8 mm, and into the contralateral side with the same volume of 0.9% saline. Adult mice are administered intraperitoneal injections of MPTP of 25 mg/kg per day for five continuous days, and the same volume of saline is injected as a control. All the animals are sacrificed at week 1, 2, 3, or 4 after the LPS or MPTP injections. The brain samples are collected for the subsequent immunohistochemistry and western blot experiments.

[1]. Langston J W, Irwin I. MPTP Neurotoxicity: An Overview and Characterization of Phases of Toxicity. II. Selective Accumulation of MPP in the Substantia Nigra: A Key to Neurotoxicity (Question). Life Sci., 1985, 36, No. 3, 201-12.

[2]. Desole M S, et al. Further investigation of allopurinol effects on MPTP-induced oxidative stress in the striatum and brain stem of the rat. Source:Pharmacol.Biochem.Behav., 1996, 54, No. 2, 377-83.

[3]. Hsu K S, et al. Potentiation of MPTP by 4-Phenylpyridine on the Neuromuscular Blockade in Mouse Phrenic Nerve-Diaphragm. Neuropharmacology, 1993, 32, No. 9, 877-83.

[4]. Sun XL, et al. Gas1 up-regulation is inducible and contributes to cell apoptosis in reactive astrocytes in the substantia nigra of LPS and MPTP models. J Neuroinflammation. 2016 Jul 8;13(1):180.

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MOLECULAR FORMULA :

C12-H15-N.Cl-H

MOLECULAR WEIGHT :

209.74

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 :

72 mg/kg

TOXIC EFFECTS :

Behavioral - tremor Behavioral - convulsions or effect on seizure threshold Behavioral - changes in motor activity (specific assay)

REFERENCE :

BEXBAN Bulletin of Experimental Biology and Medicine (English Translation). Translation of BEBMAE. (Plenum Pub. Corp., 233 Spring St., New York, NY 10013) V.41- 1956- Volume(issue)/page/year: 105,470,1988

TYPE OF TEST :

LD50 - Lethal dose, 50 percent kill

ROUTE OF EXPOSURE :

Subcutaneous

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

53800 ug/kg

TOXIC EFFECTS :

Behavioral - convulsions or effect on seizure threshold Behavioral - changes in motor activity (specific assay) Gastrointestinal - changes in structure or function of salivary glands

REFERENCE :

JPETAB Journal of Pharmacology and Experimental Therapeutics. (Williams & Wilkins Co., 428 E. Preston St., Baltimore, MD 21202) V.1- 1909/10- Volume(issue)/page/year: 247,531,1988 ** OTHER MULTIPLE DOSE TOXICITY DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

SPECIES OBSERVED :

Rodent - mouse

DOSE/DURATION :

150 mg/kg/5D-I

TOXIC EFFECTS :

Brain and Coverings - other degenerative changes Nutritional and Gross Metabolic - changes in metals, not otherwise specified Biochemical - Neurotransmitters or modulators (putative) - dopamine in striatum

REFERENCE :

PHTOEH Pharmacology and Toxicology (Copenhagen). (Munksgaard International Pub., POB 2148, DK-1016 Copenhagen K, Denmark) V.60- 1987- Volume(issue)/page/year: 76,348,1995 ** REPRODUCTIVE DATA **

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intraperitoneal

DOSE :

40 mg/kg

SEX/DURATION :

female 15 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - extra-embryonic structures (e.g., placenta, umbilical cord) Reproductive - Effects on Embryo or Fetus - fetotoxicity (except death, e.g., stunted fetus)

REFERENCE :

TXCYAC Toxicology. (Elsevier Scientific Pub. Ireland, Ltd., POB 85, Limerick, Ireland) V.1- 1973- Volume(issue)/page/year: 67,63,1991

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Subcutaneous

DOSE :

25 mg/kg

SEX/DURATION :

female 17 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Embryo or Fetus - maternal-fetal exchange

REFERENCE :

JONRA9 Journal of Neurochemistry. (Raven Press, 1185 Ave. of the Americas, New York, NY 10036) V.1- 1956- Volume(issue)/page/year: 55,1427,1990

TYPE OF TEST :

TDLo - Lowest published toxic dose

ROUTE OF EXPOSURE :

Intramuscular

DOSE :

35 mg/kg

SEX/DURATION :

female 12-18 day(s) after conception

TOXIC EFFECTS :

Reproductive - Effects on Newborn - biochemical and metabolic Biochemical - Enzyme inhibition, induction, or change in blood or tissue levels - other hydrolases

REFERENCE :

LIFSAK Life Sciences. (Pergamon Press Inc., Maxwell House, Fairview Park, Elmsford, NY 10523) V.1-8, 1962-69; V.14- 1974- Volume(issue)/page/year: 48,217,1991