DL-AP4 Sodium salt

The effects of a series of omega-phosphonic alpha-carboxylic amino acids on electrically evoked and excitant amino acid-induced responses in isolated spinal cord preparations.[Pubmed:7042024]

Br J Pharmacol. 1982 Jan;75(1):65-75.

1 The depressant actions on evoked electrical activity and the excitant amino acid antagonist properties of a range of omega-phosphonic alpha-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 selectivity 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 microM 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 (-)-forms 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 he (-)-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.

Antagonism of excitatory amino acid-induced responses and of synaptic excitation in the isolated spinal cord of the frog.[Pubmed:316343]

Br J Pharmacol. 1979 Dec;67(4):591-603.

1. A range of compounds has been tested for excitatory amino acid agonist or antagonist activity and for effects on synaptic activity on isolated hemisected spinal cords of frogs. 2. L-Monoamino dicarboxylic acids of chain length up to 8 carbon atoms (L-alpha-aminosuberate) were all agonists. 3. Within a series of D-monoamino dicarboxylic acids, and with diamino dicarboxylic acids (mainly unresolved mixtures of diasteroisomers), there was a progression from agonist activity, for compounds of chain length equal to or shorter than glutamate, to antagonist activity, for compounds of longer chain length equal to or shorter than glutamate, to antagonist activity, for compounds of longer chain length, D-alpha-Aminosuberate (D alpha SD) was the most potent antagonist. 4. The antagonist actions of these substances showed a Mg2+--like selectivity with respect to depolarizations produced by different excitants. N-methyl-D-aspartate (NMDA) was the most susceptible agonist and quisqualate and kainate the least susceptible. Responses to other excitatory amino acids, including L-glutamate and L-aspartate, showed intermediate sensitivity to the antagonists. 5. A parallelism was observed between the relative potencies of mono- and diamino dicarboxylic acids as NMDA antagonists and their relative potencies as depressants of synaptic responses. 6. The results support the concept of different types of excitatory amino acid receptors, with NMDA and its antagonists acting predominantly on one type. These NMDA receptors are probably transmitter receptors activated by an excitatory amino acid transmitter.