A novel analgesic compound OT-7100 attenuates nociceptive responses in animal models of inflammatory and neuropathic hyperalgesia: A possible involvement of adenosinergic anti-nociception

We studied the effects of OT-7100 (5-n-butyl-7-(3,4,5-trimethoxybenzoylamin o)pyrazolo [1,5-a]pyrimidine), a novel analgesic compound, on the inhibitor y action of adenosine on the contraction of guinea pig ileum and investigat ed 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 muM significantly enhanced the inhibito ry 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 su bstance P and in the Bennett model was significantly suppressed by coadmini stration of the adenosine A(1) antagonist DPCPX (0.01 or 0.1 pmol/animal, i .t.), while OT-7100 without DPCPX significantly increased the nociceptive t hreshold in each rat model. OT-7100 (3, 10 and 30 mg/kg per day, p.o.) sign ificantly inhibited the mechanical nociceptive threshold in the injured paw in the Chung model. OT-7100 (30 mg/kg, p.o.) significantly decreased the n umber of Fos-LI neurons in the spinal dorsal horn in the Bennett model. The se finding suggest that OT-7100 inhibits hyperalgesia in these animal model s possibly by enhancing adenosinergic neurotransmission in the dorsal horn, although we still lack direct evidence for it.