The spinal antinociceptive effects of a novel competitive AMPA receptor antagonist, YM872, on thermal or formalin-induced pain in rats.
Alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor antagonists have spinally mediated analgesic effects on acute nociception; however, their current formulations are not water-soluble and have toxic side effects. A new competitive AMPA antagonist, YM872 (2,3-dioxo-7-[1H-imidazol-1-yl]-6-nitro-1,2,3,4-tetrahydro-1-quinoxal inyl acetic acid) is water-soluble and may have fewer side effects. The purpose of this study was to investigate the analgesic effects of YM872 on both acute thermal and irritant-induced pain. Sprague-Dawley rats were implanted with chronic lumbar intrathecal catheters and were tested for their tail withdrawal response by the tail flick test and for their paw flinches by formalin injection after the intrathecal administration of YM872. The tail flick latency increased dose-dependently with a 50% effective dose (ED50) value of 1.0 microg. The number of flinches in both Phase 1 and Phase 2 of the formalin test decreased with increasing dose of YM872. ED50 values were 0.24 microg in Phase 1 and 0.21 microg in Phase 2. YM872 10 and 30 microg induced motor disturbance and flaccidity. In rats, the intrathecal administration of YM872 had analgesic effects on both acute thermal and formalin-induced nociceptions. Transient motor disturbance and flaccidity occurred only with large doses. YM872 may have potential in the clinical management of both acute and chronic pain.


CONCLUSIONS
A novel alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor antagonist, YM872, may have an analgesic effect on both acute and chronic pain when administered intrathecally.
Nishiyama
T
T
Department of Anesthesiology, Harbor-University of California, Los Angeles Medical Center, Torrance, USA.
Gyermek
L
L
Lee
C
C
Kawasaki-Yatsugi
S
S
Yamaguchi
T
T
D018712:Analgesics, Non-Narcotic / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005557:Formaldehyde; D007093:Imidazoles / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000037:antagonists & inhibitors*; D013116:Spinal Cord / Q000187:drug effects*
D018712:Analgesics, Non-Narcotic; D007093:Imidazoles; D011810:Quinoxalines; D018091:Receptors, AMPA; C110629:YM 872; D005557:Formaldehyde