The action of a series of glutamic acid analogues on Helix neuronal glutamate receptors.

1. Intracellular recordings were made from identified Helix central neurones, sensitive to L-glutamate. 2. Out of a range of substituted glutamate analogues, only the L- and D-isomers of thio-glutamate possessed clear glutamate-like activity. 3. On neurones excited by L-glutamate, the EC50 values for L-glutamate, gamma-thio-L-glutamate and gamma-thio-D-glutamate were 30 microM, 20 microM and greater than 1 mM, respectively. 4. On neurones inhibited by L-glutamate, the EC50 values for L-glutamate, gamma-thio-L-glutamate and gamma-thio-D-glutamate were 6.0 microM, 0.7 microM and greater than 200 microM, respectively. 5. It is concluded that, unlike the situation with thio derivatives of GABA, thio derivatives of glutamate possess potent glutamate-like activity.