Herein is described a new class of selective σ1 ligands consisting of tetrahydroisoquinoline- hydantoin (Tic-hydantoin) derivatives. Compound 3a has high affinity (IC50= 16nM) for the σ1 receptor and is selective in a large panel of therapeutic targets. This first study presents structural changes around the Tic-hydantoin core, leading to a Tic-hydantoin analogue with a higher σ1 affinity (IC50≈ 1nM).