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

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Abstract
1 The depressant actions on evoked electrical activity and the excitant amino acid antagonist properties of a range of ω-phosphonic α-carboxylic amino acids have been investigated in the isolated spinal cord preparations of the frog or immature rat. 2 When tested on dorsal root-evoked ventral root potentials, members of the homologous series from 2-amino-5-phosphonovaleric acid to 2-amino-8-phosphonooctanoic acid showed depressant actions which correlated with the ability of the substances to antagonize selectively motoneuronal depolarizations induced by N-methyl-d-aspartate. 3 2-Amino-5-phosphonovalerate was the most potent substance of the series giving an apparent KD of 1.4 μm for the antagonism of responses to N-methyl-d-aspartate. 4 A comparison of the (+)- and (—)-forms of 2-amino-5-phosphonovalerate indicated that the N-methyl-d-aspartate antagonist activity and the neuronal depressant action of this substance were both due mainly to the (—)-isomer. 5 The (—)- and (+)-forms of 2-amino-4-phosphonobutyrate had different actions. The (—)-form of this substance had a relatively weak and non-selective antagonist action on depolarizations induced by N-methyl-d-aspartate, quisqualate and kainate and a similarly weak depressant effect when tested on evoked electrical activity. The (+)-form was more potent than the (—)-form in depressing electrically evoked activity but did not antagonize responses to amino acid excitants. At concentrations higher than those required to depress electrically evoked activity, the (+)-form produced depolarization. This action was blocked by 2-amino-5-phosphonovalerate.