Attenuation of hyperalgesia by LY235959, a competitive N-methyl-D-aspartate receptor antagonist.
N-methyl-D-aspartate (NMDA) receptor antagonists may be of value in the management of hyperalgesia. LY235959, a competitive NMDA receptor antagonist, at doses of 0.001 and 0.003 nmol, intrathecally (i.t.) blocked the hyperalgesia induced by 11.1 nmol of NMDA in rats prepared with a chronic i.t. cannula. However, LY235959 does not block the hyperalgesia produced by kainic acid (a non-NMDA glutamate receptor agonist) providing evidence of its selectivity for the NMDA receptor. Using the formalin nociceptive test, 0.001 nmol LY235959 (i.t.) significantly reduced the number of Phase 2 flinches by about 80%. LY235959 can also reduce the flinching in Phase 2 by 30% when given subcutaneously (s.c.) at the lowest dose which does not produce motor deficits (20 mmol/kg). Thus, LY235959 (i.t. or s.c.) has NMDA receptor antagonist activity as defined by its ability to prevent hyperalgesia and formalin-induced central sensitization. Moreover, it is a much more potent antihyperalgesic after i.t. as compared to s.c. administration.
Department of Pharmacology, LC-524, Weill Medical College of Cornell University, 1300 York Ave, New York, NY 10021, USA.
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Davis
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Inturrisi
D000818:Animals; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D006358:Hot Temperature; D006930:Hyperalgesia / Q000139:chemically induced / Q000517:prevention & control*; D007278:Injections, Spinal; D007546:Isoquinolines / Q000494:pharmacology*; D008297:Male; D016202:N-Methylaspartate; D010147:Pain Measurement / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000502:physiology; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D007546:Isoquinolines; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; C088643:LY 235959