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A neuroprotective agent, T-817MA (1-{3-[2-(1-benzothiophen-5-yl)ethoxy]propyl} azetidin-3-ol maleate), prevents 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity in mice.
Neuropharmacology. 2008 Oct; 55(5):654-60.N

Abstract

T-817MA (1-{3-[2-(1-benzothiophen-5-yl)ethoxy]propyl} azetidin-3-ol maleate) is a candidate therapeutic agent for Alzheimer's disease that inhibits oxidative stress and nitric oxide-induced neurotoxicity and acts as a neurotrophic factor. The present study examines the effect of T-817MA on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurotoxicity in C57BL/6J mice. MPTP treatment (10mg/kg, s.c.x4 at 2-h intervals) impaired rotarod performance, and T-817MA improved this deficit. MPTP treatment also decreased dopamine levels and tyrosine hydroxylase immunostaining in the substantia nigra (SNc) and striatum. Pretreatment with T-817MA (10 and 30mg/kg as T-817, p.o.) attenuated these decreases in dopamine levels and tyrosine hydroxylase immunoreactivity, but did not affect brain levels of 1-methyl-4-phenylpyridinium ion, an active metabolite of MPTP. The protective effect was almost complete in the SNc, but only partial in the striatum. MPTP increased levels of the lipid peroxidation product, thiobarbituric acid reactive substance, only in the midbrain, which could be blocked by T-817MA. MPTP caused microglial activation both in the SNc and striatum, but T-817MA did not affect the activation of microglia. These results suggest that T-817MA protects against MPTP-induced neurotoxicity by blocking lipid peroxidation in the SNc, and imply that this compound may be useful for treating neurodegenerative disorders related to oxidative stress, such as Parkinson's disease.

Authors+Show Affiliations

Laboratory of Medicinal Pharmacology, Graduate School of Pharmaceutical Sciences, Osaka University, Osaka 565-0871, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18573265

Citation

Kawasaki, Toshiyuki, et al. "A Neuroprotective Agent, T-817MA (1-{3-[2-(1-benzothiophen-5-yl)ethoxy]propyl} Azetidin-3-ol Maleate), Prevents 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Neurotoxicity in Mice." Neuropharmacology, vol. 55, no. 5, 2008, pp. 654-60.
Kawasaki T, Ago Y, Kitao T, et al. A neuroprotective agent, T-817MA (1-{3-[2-(1-benzothiophen-5-yl)ethoxy]propyl} azetidin-3-ol maleate), prevents 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity in mice. Neuropharmacology. 2008;55(5):654-60.
Kawasaki, T., Ago, Y., Kitao, T., Nashida, T., Takagi, A., Takuma, K., & Matsuda, T. (2008). A neuroprotective agent, T-817MA (1-{3-[2-(1-benzothiophen-5-yl)ethoxy]propyl} azetidin-3-ol maleate), prevents 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity in mice. Neuropharmacology, 55(5), 654-60. https://doi.org/10.1016/j.neuropharm.2008.05.032
Kawasaki T, et al. A Neuroprotective Agent, T-817MA (1-{3-[2-(1-benzothiophen-5-yl)ethoxy]propyl} Azetidin-3-ol Maleate), Prevents 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced Neurotoxicity in Mice. Neuropharmacology. 2008;55(5):654-60. PubMed PMID: 18573265.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A neuroprotective agent, T-817MA (1-{3-[2-(1-benzothiophen-5-yl)ethoxy]propyl} azetidin-3-ol maleate), prevents 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced neurotoxicity in mice. AU - Kawasaki,Toshiyuki, AU - Ago,Yukio, AU - Kitao,Tatsuya, AU - Nashida,Tetsuaki, AU - Takagi,Akiko, AU - Takuma,Kazuhiro, AU - Matsuda,Toshio, Y1 - 2008/06/05/ PY - 2008/04/11/received PY - 2008/05/12/revised PY - 2008/05/27/accepted PY - 2008/6/25/pubmed PY - 2009/1/16/medline PY - 2008/6/25/entrez SP - 654 EP - 60 JF - Neuropharmacology JO - Neuropharmacology VL - 55 IS - 5 N2 - T-817MA (1-{3-[2-(1-benzothiophen-5-yl)ethoxy]propyl} azetidin-3-ol maleate) is a candidate therapeutic agent for Alzheimer's disease that inhibits oxidative stress and nitric oxide-induced neurotoxicity and acts as a neurotrophic factor. The present study examines the effect of T-817MA on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurotoxicity in C57BL/6J mice. MPTP treatment (10mg/kg, s.c.x4 at 2-h intervals) impaired rotarod performance, and T-817MA improved this deficit. MPTP treatment also decreased dopamine levels and tyrosine hydroxylase immunostaining in the substantia nigra (SNc) and striatum. Pretreatment with T-817MA (10 and 30mg/kg as T-817, p.o.) attenuated these decreases in dopamine levels and tyrosine hydroxylase immunoreactivity, but did not affect brain levels of 1-methyl-4-phenylpyridinium ion, an active metabolite of MPTP. The protective effect was almost complete in the SNc, but only partial in the striatum. MPTP increased levels of the lipid peroxidation product, thiobarbituric acid reactive substance, only in the midbrain, which could be blocked by T-817MA. MPTP caused microglial activation both in the SNc and striatum, but T-817MA did not affect the activation of microglia. These results suggest that T-817MA protects against MPTP-induced neurotoxicity by blocking lipid peroxidation in the SNc, and imply that this compound may be useful for treating neurodegenerative disorders related to oxidative stress, such as Parkinson's disease. SN - 0028-3908 UR - https://www.unboundmedicine.com/medline/citation/18573265/A_neuroprotective_agent_T_817MA__1_{3_[2__1_benzothiophen_5_yl_ethoxy]propyl}_azetidin_3_ol_maleate__prevents_1_methyl_4_phenyl_1236_tetrahydropyridine_induced_neurotoxicity_in_mice_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(08)00167-6 DB - PRIME DP - Unbound Medicine ER -