Inhibitors of Monoamine Oxidase V: Effect of Substitution on the Transport of Tetrahydro-β-Carboline Analogs to Mouse Brain

Methyl substitution on the indolic nitrogen and halogen substitution on the indole nucleus of tetrahydro-β-carbolines were found to facilitate the transport of compounds into the brain. A correlation between the brain accumulation, the pKa, and the partition coefficient has been made. The 8-chloro-9-methyl-1,2,3,4-tetrahydro-β-carboline was assayed with mitochondrial monoamine oxidase from mouse brain and liver. Its inhibitory activity was two-fold greater than that reported using bovine liver enzyme.