pH- and time-dependent inhibition of rat kidney neutral endoprotease 24.11 by thiorphan and phosphoramidon

The potencies of thiorphan and phosphoramidon as inhibitors of neutral endopeptidase 24.11 (NEP) are significantly affected by pH. Thiorphan and phosphoramidon are 10- and 150-fold more potent, respectively, when measured at pH 6.5 than at pH 8.5. The kinetic characteristics of these two inhibitors are different. NEP activity is readily inhibited by phosphoramidon upon mixing, while thiorphan becomes a more potent inhibitor only after preincubation with the enzyme.