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 m anagement of hyperalgesia. LY235959, a competitive NMDA receptor antagonist , at doses of 0.001 and 0.003 nmol, intrathecally (i.t.) blocked the hypera lgesia induced by 11.1 nmol of NMDA in rats prepared with a chronic i.t. ca nnula. However, LY235959 does not block the hyperalgesia produced by kainic acid (a non-NMDA glutamate receptor agonist) providing evidence of its sel ectivity for the NMDA receptor. Using the formalin nociceptive test, 0.001 nmol LY235959 (i.t.) significantly reduced the number of Phase 3 flinches b y 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 ant agonist activity as defined by its ability to prevent hyperalgesia and form alin-induced central sensitization. Moreover, it is a much more potent anti hyperalgesic after i.t. as compared to s.c. administration. (C) 2001 Elsevi er Science BSI. All rights reserved.