Tsuneo Yasuda1,*, Keiichiro Okamoto2, Takeshi Iwamoto1, Shinya Miki1, Norihiro Yoshinaga1, Seiji Sato1, Koichi Noguchi3 and Emiko Senba2
1Nutrition Research Institute, Otsuka Pharmaceutical Factory, Inc., 115 Tateiwa, Muya-cho, Naruto, Tokushima 772-8601, Japan
2Department of Anatomy and Neurobiology, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-8509, Japan
3Department of Anatomy and Neuroscience, Hyogo College of Medicine, 1-1 Mukogawa-cho, Nishinomiya, Hyogo 663-8501, Japan
*Corresponding author. FAX: +81-886-86-8176, E-mail: yasudatn@otsukakj.co.jp
Abstract: We studied the effects of OT-7100 (5-n-butyl-7-(3,4,5-trimethoxybenzoylamino)pyrazolo [1,5-a]pyrimidine), a novel analgesic compound, on the inhibitory action of adenosine on the contraction of guinea pig ileum and investigated the effects of OT-7100 on the nociceptive responses in animal models of inflammatory and peripheral neuropathic hyperalgesia and decreases spinal c-Fos expression. OT-7100 at 0.3-3 mM significantly enhanced the inhibitory effect of adenosine on the contraction of guinea pig ileum. The efficacy of OT-7100 (1, 3 or 10 mg/kg, p.o.) on hyperalgesia induced by yeast or substance P and in the Bennett model was significantly suppressed by coadministration of the adenosine A1 antagonist DPCPX (0.01 or 0.1 pmol/animal, i.t.), while OT-7100 without DPCPX significantly increased the nociceptive threshold in each rat model. OT-7100 (3, 10 and 30 mg/kg per day, p.o.) significantly inhibited the mechanical nociceptive threshold in the injured paw in the Chung model. OT-7100 (30 mg/kg, p.o.) significantly decreased the number of Fos-LI neurons in the spinal dorsal horn in the Bennett model. These finding suggest that OT-7100 inhibits hyperalgesia in these animal models possibly by enhancing adenosinergic neurotransmission in the dorsal horn, although we still lack direct evidence for it.
Keywords: Adenosine, OT-7100, Hyperalgesia, Analgesic
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