• 1
    A series of compounds structurally related to glutamic acid has been tested on frog and rat spinal neurones. The substances were added to procaine-containing medium bathing the isolated hemisected spinal cord of the frog, and their potencies in depolarizing motoneurones were assessed by the magnitude of the potential produced in the ventral root. The electrophoretic technique was used to administer the substances around single interneurones of the rat spinal cord and the relative potencies of the compounds as excitants assessed by the magnitude of the currents required to produce similar rates of neuronal firing.
  • 2
    Parallel structure-activity relations were observed in the two series of experiments, suggesting that the receptors for excitatory amino acids on frog and rat spinal neurones are similar.
  • 3
    Quisqualate, domoate and kainate were the strongest excitants in both animals, with potencies around two orders of magnitude higher than that of l-glutamate.
  • 4
    2,4,5-Trihydroxyphenylalanine (6-OH-DOPA) was a stronger excitant and l-3,4-dihydroxyphenylalanine (l-DOPA) a weaker excitant than l-glutamate on frog spinal motoneurones. The former compound was also a more potent convulsant than l-glutamate on intraventricular injection into mouse brain. The lack of activity of 6-OH-DOPA on electrophoretic administration was attributed to oxidation.
  • 5
    Unlike the majority of amino acid excitants, several of the compounds shown in the present work to have moderate excitatory activity are not anionic at physiological pH. This indicates either that two negatively charged groups are not essential for interaction with a common excitatory receptor, or that more than one type of receptor is involved in the actions demonstrated.