Electrostatic and conformational analysis of piracetam and cyclo-L-prolylglycine to explain their potency difference

The molecular electrostatic potential of the classical nootropic drug piracetam in several of its probable conformations was shown to resemble that of the neuropeptide cyclo-L-prolylglycine in its rigidly fixed conformation. Furthermore, the probability of observing this specific conformation was found to be close to the activity ratio of piracetam to cyclo-L-prolylglycine. These results support the previously proposed hypothesis that cyclo-L-prolylglycine is an endogenous analog of piracetam.