4(R)- And 4(S)-(5-phenylpentyl)-glutamic Acids Attenuate Excitatory Postsynaptic Potential on Hippocampus without Inhibiting Postsynaptic NMDA and AMPA Receptors

The electrophysiological effects of 4(R)- and 4(S)-(5-phenylpentyl)-glutamic acids (C _5R and C _5S analogues) were investigated. In the presence of 5 μM C _5R or C _5S , excitatory postsynaptic potentials (EPSPs), elicited by stimulating the Schaffer collateral-commissural pathway, recorded in the hippocampal CA1 region on rat brain slices were reduced by more than 50% of the control. Both the NMDA receptor-and the non-MNDA receptor-mediated components of the EPSP were attenuated to the similar extent. The blockade of the presynaptic input, by 0.5 μM tetrodotoxin (TTX), resulted in that C ₅ analogues no longer inhibited the depolarization induced by AMPA or NMDA on brain slices. On the other hand, the AMPA- and NMDA-induced whole cell inward current of the dissociated hippocampal neurons was not affected by the presence of C ₅ analogues, investigated with the whole cell patch-clamping technique. These results suggest that the site of the inhibitory action of C _5R and C _5S may be at the presynaptic termini and that the release of the excitatory neurotransmitter, most likely the glutamate, may be tampered.