The NMDA receptor plays a key role in a wide range of physiological and pathological processes. Recent cloning and expression studies have demonstrated that the receptor is composed of a number of subunits arranged as a hetero-oligomer. This study concentrated on non-competitive NMDA antagonists which bind within the ion-channel, in particular the novel compound, FR115427 ((+)-1-methyl-l-phenyl-1,2,3,4-tetrahydroisoquinoline). Initial experiments used a [³H]MK801 binding assay to compare FR115427 with MK801. FR115427 was subsequently tritiated, and assays developed to allow further characterisation. The requirements for binding at the ion-channel site were studied by measuring the affinity of a number of FR115427 analogues in a [³H]MK801 filtration assay. Finally, a study of the ontogeny of the human NMDA receptor was conducted, using a catalogue of post-mortem infant brains, covering the generally poorly available age range of 0-3 years. Competition studies using a filtration assay for [³H]MK801 gave a Ki value for FR115427 of 43nM. Of particular interest was the finding that the (-)isomer of FR115427 exhibited 100-fold lower affinity than FR115427 (the (+)isomer), whilst the stereoisomers of MK801 showed only a three fold separation in affinity. Maximally-stimulating concentrations of L-glutamate and glycine increased the affinity of MK801 for its binding site 6.2 and 3.4 old respectively. In contrast, the affinity of neither FR115427 nor its stereoisomer was significantly modified by the presence of either L-glutamate or glycine. For a ligand of the affinity of FR115427, rapid dissociation of specific binding might be anticipated, precluding the use of non-equilibrium separation of bound and free ligand.