Attenuation of hyperalgesia by LY235959, a competitive N-methyl-D-aspartate receptor antagonist.

Abstract

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.

• Authors: A M Davis, C E Inturrisi
• Journal: Brain research (Brain Res) Vol. 894 Issue 1 Pg. 150-3 (Mar 09 2001) ISSN: 0006-8993 [Print] Netherlands
• PMID: 11245826 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Excitatory Amino Acid Agonists
• Excitatory Amino Acid Antagonists
• Isoquinolines
• Receptors, N-Methyl-D-Aspartate
• N-Methylaspartate
• LY 235959

Topics

• Animals
• Excitatory Amino Acid Agonists
• Excitatory Amino Acid Antagonists (pharmacology)
• Hot Temperature
• Hyperalgesia (chemically induced, prevention & control)
• Injections, Spinal
• Isoquinolines (pharmacology)
• Male
• N-Methylaspartate
• Pain Measurement (drug effects)
• Rats
• Rats, Sprague-Dawley
• Receptors, N-Methyl-D-Aspartate (antagonists & inhibitors, physiology)
• Spinal Cord (drug effects, physiology)