L-Glutamic acid (Glu) and L-aspartic acid (Asp) are putative excitatory transmitters in the mammalian central nervous system (CNS)1–3. Receptors at Glu- and Asp-mediated synapses are presumably different4,5, and a prerequisite for the identification and characterisation of such sites is the availability of specific antagonists and agonists. Among various potential Glu and Asp antagonists3–6 Glu diethyl ester (GDEE)7–9 and (D)-α-aminoadipic acid (α-AA)9–13 show some selectivity, the latter particularly towards excitation by N-methyl-Asp. Kainic acid (KA), a structural analogue of Glu, is a powerful excitant of CNS neurones14–16 that seems to interact with only a small proportion of Glu receptors5. Ibotenic acid (Ibo) is a powerful neuronal excitant9,17,18 also structurally related to Glu. Excitation by Ibo, however, is readily antagonised by α-AA, whereas GDEE has little or no effect13, suggesting that Ibo preferentially activates Asp rather than Glu receptors. Furthermore, excitation of neurones by Ibo is followed by a prolonged depression of excitability18,19 which is sensitive to bicuculline methochloride19, indicating that Ibo is probably converted by decarboxylation into muscimol20 during microelectrophoretic ejection near CNS neurones. Thus, neither KA nor Ibo seem to have sufficient specificity to be useful compounds with which to study central Glu or Asp receptors. We describe here a new class of Glu agonist obtained by structural manipulation of Ibo (Table 1). Elongation of the side chain of Ibo by an additional methylene group and introduction of different ring substituents have led to isoxazole amino acids with carboxyl groups resistant to decarboxylation. A further aim of this homologation was to convert the apparent Asp agonist Ibo into a Glu agonist.