Synthesis of deuterium and tritium labelled (RS)-2-Amino-3-(5-tert-butyl-3-hydroxy-4-isoxazolyl)-propionic acid (ATPA), a selective kainic acid receptor agonist

(RS)-2-Amino-3-(5-tert-butyl-3-hydroxy-4-isoxazolyl)propionic acid (ATPA) is an excitatory amino acid receptor agonist showing selectivity for the kainic acid receptor subtype GluR5. As part of the pharmacological characterization of GluR5 receptors, we now report the synthesis of [ 3 H]ATPA based on a four-step synthesis using 5-tert-butyl-3-methoxy-4-isoxazolylcarbaldehyde as the starting material. Using this synthetic procedure deuterium and tritium labelled ATPA have been prepared. [ 3 H]ATPA, with a specific activity of 17 Ci/mmol, was obtained with a radiochemical purity of 98.9%. Attempts to demonstrate specific binding of [ 3 H]ATPA under conventional rat brain membrane receptor binding conditions were unsuccessful.