Determination of the Norepinephrine Level by High-Performance Liquid Chromatography to Assess the Protective Effect of MAO-B Inhibitors Against DSP-4 Toxicity

Liquid chromatography (LC) combined with electrochemical detection (EC) is suitable for measuring oxidizable biogenic amine levels in small samples of brain tissue. The norepinephrine (NE) content in mouse hippocampus after treatment with various monoamine oxidase-B enzyme (MAO-B) inhibitors ([−]-deprenyl, [+]-rasagiline, and the noradrenergic neurotoxin N-[2-chloroethyl]-N-ethyl-2-bromobenzylamine [DSP-4]) is determined using an LC-EC method. Treatment with a single intraperitoneal dose of (-)-deprenyl (selegiline) before DSP-4 administration markedly reduces the NE depleting effect of the toxin, and (+)-rasagiline does not significantly modify the NE level decreased by the neurotoxin. The MAO-B inhibitory potency of (-)-deprenyl and (+)-rasagiline is also evaluated. Significantly reduced MAO-B enzyme activity in mouse brain and liver is measured 6 h after treatment with their single dose. (+)-Rasagiline is found to be a more potent MAO-B inhibitor than (-)-deprenyl.