Analysis of the molecular interactions of the potent analgesic S1RA with the σ1 receptor

The highly selective σ1 receptor antagonist S1RA is endowed with a surprisingly high affinity for its target protein given a missing fundamental hydrophobic pharmacophoric requirement. Here we show that, with respect to other potent σ1 ligands, S1RA is able to compensate this loss by fulfilling all other pharmacophoric requirements and by gaining in solvation energy