Shuzo Watanabe
Pfizer
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Featured researches published by Shuzo Watanabe.
Pharmacology | 2005
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
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
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
Tadashi Inoue; Shuzo Watanabe; Tatsuya Yamagishi; Yoshimasa Arano; Mikio Morita; Kaoru Shimada
Journal of Pharmacological Sciences | 2008
Yasuhiro Takeda; Takayuki Ishida; Ryuki Tsutsui; Katsuo Toide; Sachi Tanimoto-Mori; Shuzo Watanabe; Yoshihito Kanai; Chiaki Kamei
The Journal of Antibiotics | 2001
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
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
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
Shuzo Watanabe; Hideo Hirai; Yoshinao Kato; Hiroyuki Nishida; Toshiyuki Saito; Nobuji Yoshikawa; Tanya Parkinson; Yasuhiro Kojima
Archive | 2010
Tadashi Inoue; Shuzo Watanabe; Tatsuya Yamagishi; Yoshimasa Arano; Mikio Morita; Kaoru Shimada