DEVELOPMENT AND VALIDATION OF A RADIOIMMUNOASSAY FOR PD 152247 (PNQX)EQUIVALENT CONCENTRATIONS IN RAT-BRAIN MICRODIALYSATE FLUID

Glutamate is the major excitatory amino acid (EAA) neurotransmitter in the central nervous system (CN) wand its presynaptic release leads to the activation of N-methyl-D-aspartate (NMDA) and non-NMDA glutamate receptors, Through the interruption of this excitotoxic cascade, EAA a ntagonists offer the possible prevention of the neuronal cell death th at is the characteristic pathophysiology of numerous neurological diso rders, Recent research has shown that PNQX (PD 152247) is a potent ant agonist of glutamate at alpha-amino-3-hydroxy-5-methyl-4-isoxazole pro pionic acid (AMPA) receptors, In preclinical studies, PNQX has demonst rated efficacious neuroprotective properties against glutamate-induced injury; and it is currently in development as a neuroprotective agent in the event of cerebral ischemia. To assist in the evaluation of PNQ X as a potential neuroprotective agent, and to quantitate possible bra in excellular fluid levels of PD 152247 when it is administered either intravenously or directly into the brain, we have developed and valid ated a radioimmunoassay (RIA) procedure for measuring PNQX equivalent concentrations that has a limit of quantitation of 1.95 pg/tube in rat brain microdialysate fluid.