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 microM 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.