Analgesic And Anti-inflammataory Effect Of Carboxyamido-triazole

Carboxyamido-triazole(CAI) is an experimental anti-cancer agent being researched and developed by NCI which had entered clinical trial stage, and it had been apllied as a class I new drug. CAI inhibits the proliferation of endothelial cell and many tumor cell lines in vitro and it inhibits the growth and invasion of many tumor xenograft animal models. Up to now, there are many articles on the mechanisms of this agent have been published. It is indicated that the effects of CAI are mediated by its inhibition of calcium influx stimulated by bFGF, VEGF, TG and some other agents in endothelial cell and tumor cell lines.But up to now there is no report indicated that CAI has anti-inflammatory and antalgic effect. And our data show that CAI does have these effects. Further we examined the mechanisms underlying them.The methods adopted in this study:This study adopted mice formalin tests and mice writhing tests to evaluate the antinociception effect of CAI on inflammation involving pain; this study adopted tail-flick tests and hot-plate tests to evaluate the effect of CAI on pain neuro-transmission; this study adopted Naloxone-precipitated withdrawal symptoms tests to evaluate the effect of CAI on morphine-dependent mice; this study adopted mice ear edema tests to evaluate the effect of CAI on inflammation, this study adopted lymphocytes transformation test to evaluate the effect of CAI on lymphocytes proliferation.Results:1. CAI can dramatically inhibit intraperitoneal injection of 0.6% acetic acid induing mice wtithing, and dramatically inhibit injection of 0.2% formalin into the plantar surface of front paw inducing pain and CAI potentiates morphine's antalgic effect.2. CAI can significantly inhibit 2% croton oil inducing mice ear edema.3. CAI does not affect central nociception on tail-flick tests and hot-plate tests.4. CAI does not potentiates morphine-dependent on naloxone-precipitated withdrawal jumping model.5. CAI does not inhibit lymphocytes transformation.Conclusion:1. CAI has anti-inflammatory and anti-nociception activities.2. CAI's anti-inflammatory and antalgic activities are through inhibiting peripheral sensitization instead of inhibiting pain neuro-transmission.3. CAI does not inhibit lymphocytes transformation.