1 <h5>Historical perspectives</h5> 1.1 <h5>Glutamate receptors</h5> The discovery of the neuro-excitant properties of glutamate ( Hayashi 1952, 1954, Curtis et al. 1959 ) heralded the beginning of a research field spanning over 40 years. Early studies demonstrated that glutamate depolarized membranes, primarily as a result of an increase in membrane conductance to Na + ( Curtis et al. 1972, Zieglgansberger and Puil 1973, Hosli et al. 1973 ). Our understanding of the ion channels responsible for these events, their cation permeabilities, kinetic properties and involvement in synaptic transmission has advanced enormously in the last few years, particularly as a result of molecular biological and electrophysiological studies. However, initial progress in glutamate receptor research was significantly aided by advances in pharmacology. It was demonstrated that glutamate analogues such as N -methyl- d -aspartate (NMDA), quisqualate and kainate showed varying degrees of potency on subsets of neurons ( Curtis and Johnson 1974, McLennan 1983 ). In addition, glutamate analogue antagonists such as d - α -aminoadipate, γ -glutamylaminomethylsulphonate (GAMS), kynurenic acid, glutamate diethyl ester and Mg 2+ had differential effects on agonist responses ( Evans et al. 1978, McLennan and Lodge 1979, Davies and Watkins 1979, 1985, Ault et al.
Neuropharmacology – Elsevier
Published: Oct 1, 1998
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