Novel Pyrrolo[1,2-a]Pyrazines (TSPO Ligands) with Anxiolytic Activity Dependent on Neurosteroid Biosynthesis

Resumo

A series of novel pyrrolo[1,2-a]pyrazines that were ligands of 18 kDa translocator protein (TSPO) were synthesized at Zakusov SIP. The compounds N-benzyl-N-methyl-1-phenylpyrrolo[1,2-a]pyrazine-3-carboxamide (GML-1) and N-butyl-N-methyl-1-phenylpyrrolo[1,2-a]pyrazine-3-carboxamide (GML-3) were found to possess high TSPO affinity and pronounced anxiolytic activity. The anxiolytic effects of GML-1 and GML-3 in elevated plus-maze tests were completely blocked by the neurosteroidogenic-enzyme inhibitors trilostane and finasteride.