Antinociceptive activity of CP-101,606, an NMDA receptor NR2B subunit antagonist.
1. The analgesic activity of CP-101,606, an NR2B subunit-selective N-methyl-D-aspartate (NMDA) receptor antagonist, was examined in carrageenan-induced hyperalgesia, capsaicin- and 4beta-phorbol-12-myristate-13-acetate (PMA)-induced nociceptive tests in the rat. 2. CP-101,606 30 mg kg(-1), s.c., at 0.5 and 2.5 h after carrageenan challenge suppressed mechanical hyperalgesia without any apparant alternations in motor coordination or behaviour in the rat. 3. CP-101,606 also inhibited capsaicin- and PMA-induced nociceptive responses (licking behaviour) with ED50 values of 7.5 and 5.7 mg kg(-1), s.c., respectively. 4. These results suggest that inhibition of the NR2B subunit of the NMDA receptor is effective in vivo at modulating nociception and hyperalgesia responses without causing the behavioural side effects often observed with currently available NMDA receptor antagonists.
Taniguchi
K
K
Medicinal Biology Research, Central Research Division, Pfizer Inc., Aichi, Japan.
Shinjo
K
K
Mizutani
M
M
Shimada
K
K
Ishikawa
T
T
Menniti
F S
FS
Nagahisa
A
A
D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000378:metabolism; D002211:Capsaicin; D002351:Carrageenan; D018691:Excitatory Amino Acid Antagonists / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism / Q000494:pharmacology*; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy; D007279:Injections, Subcutaneous; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010147:Pain Measurement; D010880:Piperidines / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013116:Spinal Cord / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate
D018712:Analgesics, Non-Narcotic; D018691:Excitatory Amino Acid Antagonists; D010880:Piperidines; D016194:Receptors, N-Methyl-D-Aspartate; D002351:Carrageenan; C095106:traxoprodil mesylate; D013755:Tetradecanoylphorbol Acetate; D002211:Capsaicin