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-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.
Yasuda
T
T
Nutrition Research Institute, Otsuka Pharmaceutical Factory, Inc, Naruto, Tokushima, Japan. yasudatn@otsukakj.co.jp
Okamoto
K
K
Iwamoto
T
T
Miki
S
S
Yoshinaga
N
N
Sato
S
S
Noguchi
K
K
Senba
E
E
D000241:Adenosine / Q000037:antagonists & inhibitors; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D004195:Disease Models, Animal; D006168:Guinea Pigs; D006930:Hyperalgesia / Q000188:drug therapy*; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D008297:Male; D016760:Proto-Oncogene Proteins c-fos / Q000032:analysis; D011720:Pyrazoles / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018047:Receptors, Purinergic P1 / Q000502:physiology*; D013805:Theobromine / Q000031:analogs & derivatives* / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
D018712:Analgesics, Non-Narcotic; C118618:OT 7100; D016760:Proto-Oncogene Proteins c-fos; D011720:Pyrazoles; D011743:Pyrimidines; D018047:Receptors, Purinergic P1; D014970:Xanthines; C057837:3,7-dimethyl-1-propargylxanthine; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine; D013805:Theobromine