Amnestic potency of proline analogs correlates with anti-spreading depression potency.

L-Proline and some of its analogs have been shown to prevent spreading depression (SD) in the chick retina at relatively low concentrations and to impair memory processing without provoking toxic or electrophysiological disturbances. Both effects are hypothesized to be caused by inhibition of the effects of glutamate released into the extracellular space. L-Proline, its D-enantiomer, six proline analogs including two homologs (L-azetidine-2-carboxylic acid and DL-pipecolic acid), and five other compounds were examined for their effects on spreading depression and their amnestic and electrophysiological effects. L-Proline, L-baikiain, DL-3,4-dehydroproline, and L-4-hydroxyproline all reduced the incidence of SD in the chick retina and proved to be amnestic. D-Proline, L-pyroglutamic acid, L-azetidine-2-carboxylic acid, DL-pipecolic acid, L-glutamic acid diethylester, L-isoleucine and L-norleucine neither depressed SD nor caused retrograde amnesia. L-Prolyl-L-proline and L-glutamine did not depress SD at low concentrations but had significant amnestic effects. None of the listed compounds induced EEG disturbances. Implications for memory mechanisms are discussed in the light of these results.