Trends in Pharmacological Sciences
ReviewStructure-activity relationships in the development of excitatory ammo acid receptor agonists and competitive antagonists
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2016, Advances in PharmacologyCitation Excerpt :There are many different structurally related amino acids that can induce excitotoxic damage, namely N-methyl-d-aspartate, homocysteate, cysteine sulfinate, and cysteate (Olney, Ho, & Rhee, 1971). Olney proposed that the neurotoxicity of an initial series of glutamate analogues and their neuroexcitatory effects in electrophysiological studies “may be governed by similar mechanisms of action” (Curtis & Johnston, 1974; Watkins, Krogsgaard-Larsen, & Honore, 1990). The general physical environment needed for activation of different glutamate receptors has been described as follows: a positively charged group (usually, the amino acids) is found in glutamate agonists both near a negatively charged group (most often, the carboxylic acid group) and a second distant negatively charged group (Choi, 1992).