Antagonism of Excitatory Amino Acid‐induced Responses and of Synaptic Excitation in the Isolated Spinal Cord of the Frog

The pharmacological specificity of N‐methyl‐d‐aspartate receptors in rat cerebral cortex: correspondence between radioligand binding and electrophysiological measurements

“…However, a further anomaly was observed with the analogue DL-AS. In agreement with previous results with spinal cord slices (Evans et al, 1979) (Pin et al, 1984), which are very sensitive to inhibition by quisqualate (Fagg et al, 1983). The majority of compounds with inhibition profiles suggestive of a selective inhibition of NMDA-sensitive binding sites had shallow inhibition curves as reflected by the low Hill coefficents.…”

“…Nevertheless, the 6 fold difference between the relative potencies of D-glutamate in the electrophysiological and binding experiments indicates, as suggested previously (Cox et al, 1977;Lodge, 1979) (Cross et al, 1986;Lehmann et al, 1987). CPP, AP5, AP7, D-AA and D-fI-AspAmp have all been reported as selective competitive NMDA antagonists (Evans et al, 1979;Jones et al, 1984;Davies et al, 1986;Lehmann et al, 1987). This was confirmed in the present electrophysiological experiments by the fact that these compounds had little or no effect on depolarizations induced by quisqualate or kainate and gave Schild plots with slopes of 1.…”

“…Antagonists Antagonist affinities were obtained by Schild analysis (Arunlakshana & Schild, 1959) no effect on those for quisqualate ( Figure 3b) and gave Schild plots with slopes not significantly different from 1 (see Figure 4 and (Foster & Fagg, 1987a;Lehmann et al, 1987;Fagg & Baud, 1988;Murphy et al, 1988;Olverman et al, 1988a,b) and in electrophysiological experiments using several CNS regions (Evans et al, 1979;Jones et al, 1984;Harrison & Simmonds, 1985;Davies et al, 1986).…”

The EFFECTS OF a SERIES OF Ω‐PHOSPHONIC Α‐CARBOXYLIC AMINO ACIDS ON ELECTRICALLY EVOKED AND EXCITANT AMINO ACID‐INDUCED RESPONSES IN ISOLATED SPINAL CORD PREPARATIONS

“…In particular, this substance is a potent and highly selective antagonist of N-methyl-D-aspartateinduced responses (Davies, Francis, Jones & Watkins, 1981). Receptors sensitive to N-methyl-Daspartate have been implicated in spinal synaptic transmission (Evans, Francis, Hunt, Oakes & Watkins, 1979;Davies & Watkins, 1979). The actions of the lower homologues, (±)-2-amino-3-phosphonopropionate and (±)-2-amino-4-phosphonobutyrate, which are the phosphono analogues of aspartate and glutamate, respectively, are less clear.…”

The novel anticonvulsant MK‐801 binds to the activated state of the N‐methyl‐d‐aspartate receptor in rat brain

“…Of the receptor subtypes which mediate the actions of the excitatory neurotransmitters L-glutamate and Laspartate (Watkins & Evans, 1981;Foster & Fagg, 1984), the N-methyl-D-aspartate (NMDA)-preferring receptor is the best characterized, and both competitive (Evans et al, 1979;1982) and non-competitive (Lodge et al, 1983;Harrison & Simmonds, 1985) NMDA receptor antagonists have been described. ((+ )-5-methyl-10, 1 1-dihydro-5H-dibenzo [a,d]cyclohepten-5,10-imine maleate) is a novel anticonvulsant (Clineschmidt et al, 1982) which acts as a potent and selective non-competitive NMDA antagonist .…”