ABSTRACT
N-methyl-D-aspartic acid (NMDA, Figure 4.1) was initially synthesised as part of a structure-activity study aimed at obtaining aspartic (asp) and glutamic acid (glu) (Figure 4.1) analogues, which showed a degree of stereoselectivity for activation of glutamate receptors (Curtis and Watkins, 1960; Watkins, 1962). Indeed, NMDA was the most potent excitant tested at that time and, unlike asp, showed stereoselectivity, the D-form being the active isomer, while the L-form was much less potent (Curtis and Watkins, 1963). The increase in potency observed with NMDA compared to asp and glu was later ascribed to the low affinity of NMDA for the transporter responsible for the uptake of glu and asp (Balcar and Johnston, 1972). Since this time structure-activity studies have revealed agonists with greater potency than NMDA (see pp.71-73).
