The systemically administered competitive AMPA receptor antagonist, YM872,has analgesic effects on thermal or formalin-induced pain in rats

A new competitive alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor antagonist, (2,3-dioxo-7-[1H-imidazol-1-yl]-6-nitro-1,2,3,4-tetrah ydro-1-quinoxalinyl) acetic acid (YM872) has analgesic effects on acute the rmal- and formalin-induced nociception by intrathecal administration. The p urpose of this study was to determine the analgesic effects of systemically administered YM872 in both acute thermal- and irritant-induced pain. Sprag ue-Dawley rats were tested for tail withdrawal response by the tail flick t est and for paw flinches by formalin injection after intraperitoneal admini stration of YM872. The tail flick latency increased dose-dependently with a 50% effective dose value of 156.3 mu g The number of flinches in both firs t and second phases of the formalin test decreased with increasing the dose of YM872. The 50% effective dose values were 1.0 mu g in the first phase a nd 38.7 mu g in the second phase. Transiently, intraperitoneal administrati on of 1 and 10 mg of YM872 induced motor disturbance and 10 mg induced loss of pinna reflex. We conclude that intraperitoneal administration of YM872 had analgesic effects on both acute thermal and formalin-induced nociceptio ns in rats. Transient motor disturbance and loss of pinna reflex occurred o nly with large doses. Implications: Intraperitoneally administered YM872, a new alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor anta gonist, had analgesic effects on thermal- and formalin-induced pain in rats . Larger doses induced transient motor disturbance and loss of pinna reflex mediated in the brain.