An N-protected gamma-aminobutyric acid dipeptide with anticonvulsant action.
N-Pivaloyl-leucyl-gamma-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]gamma-aminobutyric acid [( U-14C]GABA). The displacement of GABA 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.
D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis*; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism; D004151:Dipeptides / Q000138:chemical synthesis*; D007700:Kinetics; D051381:Rats; D011919:Rats, Inbred Strains; D012640:Seizures; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D000927:Anticonvulsants; D004151:Dipeptides; D005680:gamma-Aminobutyric Acid; C041394:N-pivaloylleucyl-gamma-aminobutyric acid