The clinically available NMDA receptor antagonist memantine is antinociceptive on rat spinal neurones

Abstract

In anaesthetized rats antinociceptive effects of the clinically available drug memantine, an NMDA (N-methyl-D-aspartate) antagonist in vitro, were evaluated using extracellular recordings from spinal neurones with knee joint input. Memantine (1-12 mg kg-1) was applied intravenously before (control animals) or after induction of an acute knee joint inflammation which rendered spinal neurones hyperexcitable. Memantine (2 mg kg-1, i.v.) selectively reduced the responses to ionophoretic application of NMDA close to the neurone but not those to AMPA (alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid). In control animals memantine reduced the neurones' responses to noxious but not to innocuous pressure on to the knee. In rats with acute arthritis memantine reduced the responses to noxious and innocuous pressure. Thus memantine may be useful for the treatment of pain states.