Synergy between a NR2B receptor antagonist DHQ and 3-methyl-gabapentin in mice with neuropathic pain.
The synergistic effect of a selective NR2B NMDA receptor antagonist, (-)-(R)-6-{2-[4-(3-Fluorophenyl)-4-hydroxy-1-piperidinyl]-1-hydroxyethyl-3,4-dihydro-2(1H)-quinolinone (DHQ), and a alpha 2 delta ligand, 3-methyl-gabapentin (3M-GBP), was investigated in the mouse partial sciatic nerve model. The interaction was observed after administration of DHQ and 3M-GBP combination at fixed dose ratios of 1:10 and 1:30 and the dose-response curves shifted approximately 13- and 17-fold leftward, respectively, from the theoretical additive values. However, a fixed dose ratio of 1:50 resulted only in an additive effect. These results indicate the synergistic interaction between DHQ and 3M-GBP in this animal model of neuropathic pain.
Discovery Biology Research, Global Research and Development, Nagoya Laboratories, Pfizer Inc, 5-2 Taketoyo, Aichi 470-2393, Japan.
Aki
A
Imai
Masanori
M
Hizue
Katsuo
K
Toide
D000085:Acetates / Q000008:administration & dosage*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D010880:Piperidines / Q000008:administration & dosage*; D015363:Quinolones / Q000008:administration & dosage*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D020426:Sciatic Neuropathy / Q000188:drug therapy*
C420103:3-methylgabapentin; C524665:6-(2-(4-(3-fluorophenyl)-4-hydroxy-1-piperidinyl)-1-hydroxyethyl)-3,4-dihydro-2(1H)-quinolinone; D000085:Acetates; D018691:Excitatory Amino Acid Antagonists; C121001:NR2B NMDA receptor; D010880:Piperidines; D015363:Quinolones; D016194:Receptors, N-Methyl-D-Aspartate