Pyrazino[1,2-a]indoles as novel high-affinity and selective imidazoline I2 receptor ligands

Abstract 1,2,3,4-Tetrahydropyrazino[1,2- a ]indoles are described as a novel class of I 2 imidazoline receptor ligands. In particular, 8-methoxy-1,2,3,4-tetrahydropyrazino[1,2- a ]indole (8-OMe THPI; 3c ) binds with high affinity at I 2 imidazoline receptors ( K i =6.2 nM) and with exceptional (≥1000-fold) selectivity relative to its affinity for I 1 imidazoline receptors, α 2 adrenergic receptors, and 5-HT 2A and 5-HT 2C serotonin receptors.