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Riluzole (2-amino-6-trifluoromethoxy benzothiazole) attenuates MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) neurotoxicity in mice.
Neurosci Lett. 2001 Oct 12; 312(1):50-4.NL

Abstract

The protective effects of 2-amino-6-trifluoromethoxy benzothiazole (riluzole), a Na(+) channel blocker with antiglutamatergic activity were investigated in the model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced depletion of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels in mice. The mice were injected intraperitoneally (i.p.) with four administrations of MPTP (10 mg/kg) at 1 h intervals and then the brains were analyzed at 3 and 7 days after the treatments. Dopamine, DOPAC and HVA levels were significantly decreased in the striatum 3 days after MPTP treatments. Riluzole dose-dependently antagonized the MPTP-induced decrease in dopamine, DOPAC and HVA levels in the striatum. MPTP treatment also caused a severe decrease in the amount of nigral tyrosine hydroxylase protein (TH) and microtuble-associated protein 2 (MAP 2) and produced a marked increase in the striatal glial fibrillary acidic protein (GFAP). Our immunohistochemical study with TH and MAP 2 staining showed that riluzole can protect against MPTP-induced neuronal damage in the substantia nigra. Furthermore, riluzole markedly increased the striatal GFAP-positive astrocytes 3 days after MPTP treatments. These results suggest that riluzole is effective against MPTP-induced neurodegeneration of the nigrostriatal dopaminergic neuronal pathway. Our findings also may provide a rationale for the identification of astrocytes as a prominent target for the development of new therapies of Parkinson's disease.

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Authors+Show Affiliations

Araki T
Department of Clinical Pharmacology and Therapeutics, Tohoku University Graduate School of Pharmaceutical Science and Medicine, Aoba-yama, Sendai 980-8578, Japan. tsuaraki@mail.cc.tohuko.ac.jp
Muramatsu Y
No affiliation info available
Tanaka K
No affiliation info available
Matsubara M
No affiliation info available
Imai Y
No affiliation info available

MeSH

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine3,4-Dihydroxyphenylacetic AcidAnimalsAstrocytesDopamineDose-Response Relationship, DrugDown-RegulationDrug InteractionsExcitatory Amino Acid AntagonistsGlial Fibrillary Acidic ProteinGlutamic AcidHomovanillic AcidImmunohistochemistryMaleMiceMice, Inbred C57BLMicrotubule-Associated ProteinsNeostriatumNeuronsNeuroprotective AgentsParkinsonian DisordersRiluzoleSubstantia NigraTyrosine 3-Monooxygenase

Pub Type(s)

Journal Article

Language

eng

PubMed ID

11578843

Citation

Araki, T, et al. "Riluzole (2-amino-6-trifluoromethoxy Benzothiazole) Attenuates MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) Neurotoxicity in Mice." Neuroscience Letters, vol. 312, no. 1, 2001, pp. 50-4.
Araki T, Muramatsu Y, Tanaka K, et al. Riluzole (2-amino-6-trifluoromethoxy benzothiazole) attenuates MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) neurotoxicity in mice. Neurosci Lett. 2001;312(1):50-4.
Araki, T., Muramatsu, Y., Tanaka, K., Matsubara, M., & Imai, Y. (2001). Riluzole (2-amino-6-trifluoromethoxy benzothiazole) attenuates MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) neurotoxicity in mice. Neuroscience Letters, 312(1), 50-4.
Araki T, et al. Riluzole (2-amino-6-trifluoromethoxy Benzothiazole) Attenuates MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) Neurotoxicity in Mice. Neurosci Lett. 2001 Oct 12;312(1):50-4. PubMed PMID: 11578843.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Riluzole (2-amino-6-trifluoromethoxy benzothiazole) attenuates MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) neurotoxicity in mice. AU - Araki,T, AU - Muramatsu,Y, AU - Tanaka,K, AU - Matsubara,M, AU - Imai,Y, PY - 2001/10/2/pubmed PY - 2002/1/5/medline PY - 2001/10/2/entrez SP - 50 EP - 4 JF - Neuroscience letters JO - Neurosci Lett VL - 312 IS - 1 N2 - The protective effects of 2-amino-6-trifluoromethoxy benzothiazole (riluzole), a Na(+) channel blocker with antiglutamatergic activity were investigated in the model of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced depletion of dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) levels in mice. The mice were injected intraperitoneally (i.p.) with four administrations of MPTP (10 mg/kg) at 1 h intervals and then the brains were analyzed at 3 and 7 days after the treatments. Dopamine, DOPAC and HVA levels were significantly decreased in the striatum 3 days after MPTP treatments. Riluzole dose-dependently antagonized the MPTP-induced decrease in dopamine, DOPAC and HVA levels in the striatum. MPTP treatment also caused a severe decrease in the amount of nigral tyrosine hydroxylase protein (TH) and microtuble-associated protein 2 (MAP 2) and produced a marked increase in the striatal glial fibrillary acidic protein (GFAP). Our immunohistochemical study with TH and MAP 2 staining showed that riluzole can protect against MPTP-induced neuronal damage in the substantia nigra. Furthermore, riluzole markedly increased the striatal GFAP-positive astrocytes 3 days after MPTP treatments. These results suggest that riluzole is effective against MPTP-induced neurodegeneration of the nigrostriatal dopaminergic neuronal pathway. Our findings also may provide a rationale for the identification of astrocytes as a prominent target for the development of new therapies of Parkinson's disease. SN - 0304-3940 UR - https://www.unboundmedicine.com/medline/citation/11578843/Riluzole__2_amino_6_trifluoromethoxy_benzothiazole__attenuates_MPTP__1_methyl_4_phenyl_1236_tetrahydropyridine__neurotoxicity_in_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0304-3940(01)02176-0 DB - PRIME DP - Unbound Medicine ER -