Binding studies of L-Prolyl-L-leucyl-glycinamide (PLG), a novel antiparkinsonian agent, in normal human brain

In an attempt to elucidate the mechanism subserving the potential antiparkinsonian properties of L-Prolyl-L-leucyl-glycinamide (PLG) in humans, we used a radioligand binding assay to identify specific binding sites of PLG in normal human brain. ³H-PLG bound to crude membrane homogenates obtained from human striatum with high affinity and in a saturable manner (B_max = 10.04 ± 0.82 fmoles/mg^-1 protein and K_D = 3.60 ± 0.43 nM). The regional distribution profile of specific ³H-PLG binding showed that the substantia nigra exhibited the highest level of specific ³H-PLG binding, followed by striatum and hypothalamus. Pharmacologically active analogues of PLG competed for specific ³H-PLG binding with relative potencies correlating with their biological activities in vivo. The results are consistent with the hypothesis that specific PLG binding sites exist in the human brain capable of modulating the sensitivity of dopamine receptors.