Search for small molecules with antipsychotic activity based on neurotensin

A series of systemically active N-acylprolyltyrosines was constructed based on the structure of endogenous neuroleptic-like tridecapeptide neurotensin that exhibits activity on intracerebral administration. Among these dipeptides, N-caproyl-L-prolyl-L-tyrosine methyl ester (Dilept) was chosen for further development. The paper briefly describes the main concepts of Dilept design and presents new experimental data of the Dilept effects in a ‘translational’ model of schizophrenia, i.e., the deficit of prepulse inhibition caused by dopamine-mimetic apomorphine or ketamine, a noncompetitive blocker of N-methyl-D-aspartic acid. Dilept demonstrated effectiveness in this model in both intraperitoneal and oral administration, which makes it possible to predict its application as an antipsychotic agent.