Underlying Mechanism of Combined Effect of Methamphetamine and Morphine on Lethality in Mice and Therapeutic Potential of Cooling
スポンサーリンク
概要
- 論文の詳細を見る
An increase in polydrug abuse is a major problem worldwide. A previous study showed that coadministration of methamphetamine and morphine induced lethality in rodents and humans. However, the underlying mechanisms by which the lethality is increased by the coadministration of methamphetamine and morphine have not been fully understood. Therefore, the present study was designed to determine the mechanism of increased lethality induced by methamphetamine and morphine. Coadministered methamphetamine and morphine increased the lethality by more than 70% in BALB/c mice. Pretreatment with NMDA-receptor antagonists, such as MK-801 and 3-((R)-2-carboxypiperazin-4-yl) propyl-1-phosphonic acid (CPP), and benzamide [poly(ADP-ribose) polymerase (PARP) inhibitor] significantly attenuated the increased lethality induced by methamphetamine and morphine. Furthermore, the lethal effect induced by methamphetamine and morphine was completely attenuated by immediate cooling after the coadministration of methamphetamine and morphine. It has been reported that methamphetamine-induced neurotoxicity can be blocked by lowering the temperature, and this effect might be mediated by a reduction of release of free radicals. These results suggest that activation of NMDA receptors and PARP play an important role in the increased lethality induced by methamphetamine and morphine.
- 社団法人 日本薬理学会の論文
- 2005-10-20
著者
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Suzuki Tadashi
Department of Medicine and Biological Science, Graduate School of Medicine, University of Gunma
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Suzuki Tadashi
Department Of Medicine And Biological Science Graduate School Of Medicine University Of Gunma
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Sawaguchi T
Department Of Emergency Medicine Tokyo Women's Medical University
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Ito Shinobu
Vitamin C60 Bioresearch Corporation
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Ito Shinobu
Department Of Legal Medicine Tokyo Women's Medical University
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MORI Tomohisa
Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences
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SAWAGUCHI Toshiko
Department of Legal Medicine, Tokyo Women's Medical University
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Suzuki Tsutomu
Department Of Emergency Medicine Tokyo Women's Medical University
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Sawaguchi Toshiko
Department Of Anatomy Keio University
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Nomura Mutsuko
Department Of Toxicology Hoshi University School Of Pharmacy And Pharmaceutical Sciences
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NAMIKI Mizuho
Department of Emergency Medicine, Tokyo Women's Medical University
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Namiki Mizuho
Dep. Of Emergency Medicine Tokyo Women's Medical Univ. Jpn
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Namiki Mizuho
Department Of Emergency Medicine Tokyo Women's Medical University
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Mori Tomohisa
Department Of Legal Medicine Tokyo Women's Medical University
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Nomura Mutsuko
Department Of Emergency Medicine Tokyo Women's Medical University
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Suzuki Tadashi
Department Of Biology Tokyo Metropolitan University
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Suzuki Tadashi
Department Of Biology Faculty Of Science Tokyo Metropolitan University
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