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

1,2,3,4-Tetrahydropyrazino[1,2-a]indoles are described as a novel class of I2 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 I2 imidazoline receptors (Ki=6.2 nM) and with exceptional (≥1000-fold) selectivity relative to its affinity for I1 imidazoline receptors, α2adrenergic receptors, and 5-HT2A and 5-HT2C serotonin receptors.