Antinociceptive effect of the novel compound OT-7100 in a diabetic neuropathy model.
We previously reported that OT-7100 (5-n-butyl-7-(3,4,5-trimethoxybenzoylamino)pyrazolo[1,5-alpha]pyrimidine) had antinociceptive potency in various animal models. To further characterize this compound, the present study examined the effects of OT-7100 on mechanical hyperalgesia and motor nerve conduction velocity in streptozotocin-induced diabetic rats. OT-7100 significantly increased the nociceptive threshold in the diabetic rat in a dose-dependent manner. Gabapentin (anticonvulsant agent) and insulin strongly increased the nociceptive threshold but gabapentin increased it above normal levels. An aldose reductase inhibitor slightly increased the nociceptive threshold at a high dose. We also measured glucose levels and motor nerve conduction velocity in OT-7100-treated rats. Insulin decreased glucose levels but OT-7100 had no effect on glucose levels or on motor nerve conduction velocity. These results suggest that OT-7100 alleviates hyperalgesia in a diabetic neuropathy model in a different manner from gabapentin or aldose reductase inhibitor and may be a new treatment for the pain associated with peripheral nerve injury.
Miki
S
S
Nutrition Research Institute, Otsuka Pharmaceutical Factory, Inc., 115 Tateiwa, Muya-cho, Naruto, 772-8601, Tokushima, Japan. mikisn@otsukakj.co.jp
Yoshinaga
N
N
Iwamoto
T
T
Yasuda
T
T
Sato
S
S
D000085:Acetates / Q000494:pharmacology; D000588:Amines; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D003509:Cyclohexanecarboxylic Acids; D003929:Diabetic Neuropathies / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000077206:Gabapentin; D005947:Glucose / Q000378:metabolism; D006930:Hyperalgesia / Q000209:etiology / Q000517:prevention & control*; D007328:Insulin / Q000494:pharmacology; D008297:Male; D009046:Motor Neurons / Q000187:drug effects / Q000502:physiology; D009431:Neural Conduction / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D011720:Pyrazoles / Q000494:pharmacology*; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D005680:gamma-Aminobutyric Acid
D000085:Acetates; D000588:Amines; D000700:Analgesics; D003509:Cyclohexanecarboxylic Acids; D007328:Insulin; C118618:OT 7100; D011720:Pyrazoles; D011743:Pyrimidines; D005680:gamma-Aminobutyric Acid; D000077206:Gabapentin; D005947:Glucose