L-Proline and related compounds: correlation of structure, amnesic potency and anti-spreading depression potency.

The effects of L-proline, D-proline, and L-azetidine-2-carboxylic acid (L-A.2.C., the lower homolog of L-proline) have been compared in two systems. L-Proline is more potent than either analog in causing amnesia of one-trial avoidance conditioning of the 2-day-old chick and in preventing mechanically induced spreading depression in the retina isolated from 2-3-week-old chicks. The results suggest that the L-configuration and the proper molecular size are essential for the effects of L-proline upon memory and upon spreading depression. This level of specificity is greater than that involved in protein synthesis because L-A.2.C. is incorporated into protein in place of L-proline, in several protein-synthesizing systems.