A Novel Analgesic Compound OT-7100 Attenuates Nociceptive Responses in Animal Models of Inflammatory and Neuropathic Hyperalgesia: A Possible Involvement of Adenosinergic Anti-nociception

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 μ M 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.