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Featured researches published by Shuzo Watanabe.


Pharmacology | 2005

Brain but Not Spinal NR2B Receptor Is Responsible for the Anti-Allodynic Effect of an NR2B Subunit-Selective Antagonist CP-101,606 in a Rat Chronic Constriction Injury Model

Etsuko Nakazato; Aki Kato; Shuzo Watanabe

In order to examine the site of action of an NR2B subtype-selective NMDA antagonist CP-101,606, we investigated its analgesic effect in a rat model of neuropathic pain at various routes of administration. Mechanical allodynia was induced by chronic constriction injury (CCI) of the sciatic nerve in male Sprague-Dawley rats. Subcutaneous treatment of the animals with CP-101,606 at 10 mg/kg significantly inhibited CCI-induced mechanical allodynia. Intracerebroventricular injection of CP-101,606 at 10, 30 and 100 nmol also inhibited the mechanical allodynia in a dose-dependent manner, the statistically significant effect being achieved at the highest dose tested (100 nmol) without producing any behavioral abnormalities. However, intrathecal injection of CP-101,606 at a dose of 300 nmol failed to inhibit CCI-induced allodynia. A receptor binding assay using rat forebrain and spinal cord membrane preparations demonstrated that [3H]CP-101,606 bound to the brain NR2B receptor with a greater extent compared to the spinal cord one. These findings suggest that the anti-allodynia effect of CP-101,606 is ascribable to blockade of NR2B receptors at the brain, but not at the spinal cord. In contrast, intrathecal injection of a non-selective NMDA antagonist, memantine, significantly inhibited CCI-induced mechanical allodynia at a dose of 300 nmol, indicating the difference in the site of action between the non-selective NMDA antagonist and the NR2B-specific NMDA antagonist.


Bioorganic & Medicinal Chemistry Letters | 2014

Identification of a novel 2-pyridyl-benzensulfonamide derivative, RQ-00203078, as a selective and orally active TRPM8 antagonist.

Masashi Ohmi; Yuji Shishido; Tadashi Inoue; Kazuo Ando; Akiyoshi Fujiuchi; Akiko Yamada; Shuzo Watanabe; Kiyoshi Kawamura

A novel series of 2-pyridyl-benzensulfonamide derivatives have been identified as selective and orally active TRPM8 antagonists via high throughput screening (HTS). Exploration of the structure-activity relationships of compound 1 has led to the identification of RQ-00203078 (compound 36) as a highly selective, potent and orally available TRPM8 antagonist. RQ-00203078 demonstrated excellent in vivo activity in a dose dependent manner with an ED50 value of 0.65 mg/kg in the icilin-induced wet-dog shakes model in rats after oral administration and may become an important pharmacological tool for fully assessing the potential therapeutic use of the targets activated by cold stimulation.


The Journal of Antibiotics | 1998

Erinacine E as a Kappa Opioid Receptor Agonist and Its New Analogs from a Basidiomycete, Hericium ramosum

Toshiyuki Saito; Fukumatsu Aoki; Hideo Hirai; Taisuke Inagaki; Yasue Matsunaga; Tatsuo Sakakibara; Shinichi Sakemi; Suzuki Y; Shuzo Watanabe; Osamu Suga; Tetsujo Sujaku; Adam A. Smogowicz; Susan Jane Truesdell; John Wing Wong; Atsushi Nagahisa; Yasuhiro Kojima; Nakao Kojima


Archive | 2010

Aryl substituted carboxamide derivatives as calcium or sodium channel blockers

Tadashi Inoue; Shuzo Watanabe; Tatsuya Yamagishi; Yoshimasa Arano; Mikio Morita; Kaoru Shimada


Journal of Pharmacological Sciences | 2008

Studies on Somnolence in the Daytime Caused by Drugs Used for Neuropathic Pain

Yasuhiro Takeda; Takayuki Ishida; Ryuki Tsutsui; Katsuo Toide; Sachi Tanimoto-Mori; Shuzo Watanabe; Yoshihito Kanai; Chiaki Kamei


The Journal of Antibiotics | 2001

CJ-15,183, a new inhibitor of squalene synthase produced by a fungus, Aspergillus aculeatus.

Shuzo Watanabe; Hideo Hirai; Masaru Ishiguro; Takahito Kambara; Yasuhiro Kojima; Tomoyuki Matsunaga; Hiroyuki Nishida; Suzuki Y; Ayumu Sugiura; H. James Harwood; Liang Hsiung Huang; Nakao Kojima


The Journal of Antibiotics | 2001

CJ-13,981 and CJ-13,982, New Squalene Synthase Inhibitors

Shuzo Watanabe; Hideo Hirai; Takahito Kambara; Yasuhiro Kojima; Hiroyuki Nlshida; Ayumu Sugiura; Yuji Yamauchi; Nobuji Yoshikawa; H. James Harwood; Liang Hsiung Huang; Nakao Kojima


Bioorganic & Medicinal Chemistry Letters | 2007

Discovery of (-)-6-[2-[4-(3-fluorophenyl)-4-hydroxy-1-piperidinyl]-1-hydroxyethyl]-3,4-dihydro-2(1H)-quinolinone--a potent NR2B-selective N-methyl D-aspartate (NMDA) antagonist for the treatment of pain.

Makoto Kawai; Kazuo Ando; Yukari Matsumoto; Isao Sakurada; Masako Hirota; Hiroshi Nakamura; Atsuko Ohta; Masaki Sudo; Kazunari Hattori; Tadashi Takashima; Masanori Hizue; Shuzo Watanabe; Isami Fujita; Mayumi Mizutani; Mitsuhiro Kawamura


The Journal of Antibiotics | 2001

CJ-19,784, a New Antifungal Agent from a Fungus, Acanthostigmella sp.

Shuzo Watanabe; Hideo Hirai; Yoshinao Kato; Hiroyuki Nishida; Toshiyuki Saito; Nobuji Yoshikawa; Tanya Parkinson; Yasuhiro Kojima


Archive | 2010

Dérivés de carboxamide substitués par aryle comme inhibiteurs des canaux calciques ou sodiques

Tadashi Inoue; Shuzo Watanabe; Tatsuya Yamagishi; Yoshimasa Arano; Mikio Morita; Kaoru Shimada

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