New class of glutamate agonist structurally related to ibotenic acid

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