2-(Phosphonomethyl)-pentanedioic Acid

2-(Phosphonomethyl)-pentanedioic acid (2-PMPA) is a potent inhibitor of glutamate carboxypeptidase II (GCP II), also known as N-acetylated a-linked dipeptidase (NAALADase), with a Ki value of 98 pM for release of glutamate from the NAALADase peptide substrate N-acetylasparatylglutamate (NAAG).{38879} It is selective for GCP II/NAALADase over a panel of 100 receptors, transporters, ion channels, and enzymes at a concentration of 10 ?M.{7392} 2-PMPA is neuroprotective against hypoxia (EC50 = 8.4 ?M), but not veratridine-induced injury, in neuron-enriched primary cultures from rat embryo cerebellum.{38880} In vivo, 2-PMPA reduces neuronal cell death induced by middle cerebral artery occlusion via increases in NAAG expression and reduction of glutamate in rats.{7392} 2-PMPA (100 mg/kg) blocks the conditioned place preference response to cocaine, but not food, in male rats.{38881} It reduces the number of flinches induced by formalin injection into the footpad of mice when administered at a dose of 10 ?g per animal, an effect that is reversed by the group II metabotropic glutamate receptor antagonist LY341495.{38878} 2-PMPA also decreases severity and delays onset of experimental autoimmune encephalomyelitis (EAE) in mice.{38882}