An N-Protected γ-Aminobutyric Acid Dipeptide with Anticonvulsant Action

Abstract: N -Pivaloyl-leucyl–γ-aminobutyric acid (PLG) is a synthetic dipeptide with a partition coefficient of 1.67 in an ethyl acetate/water system that partially inhibits the synaptosomal uptake and activates the release of [U- ¹⁴C]-γ-aminobutyric acid ([U-¹⁴C]GABA). The displacement of GAB A from crude synaptic membranes by PLG occurs with an IC₅₀ of 10⁻⁵ M . The compound has the capacity to cross the blood-brain barrier and increase central GABA levels. Its ED₅₀ on cardiazol-induced convulsions is 60-65 mg/kg. PLG is resistant to hydrolysis by chymotrypsin and partially inhibits the proteolytic activity of trypsin.