Two series of σ(1) ligands with a spiro[[2]benzopyran-1,3'-pyrrolidine] (3) and a spiro[[2]benzofuran-1,3'-pyrrolidine] (4) framework were synthesized and pharmacologically evaluated. Several reaction steps were considerably improved by microwave irradiation. The σ(1) affinity of the spirocyclic ligands correlates nicely with the benzene-N-distance, i.e. 2 < 3 < 4 < 1. The σ(1) affinity of both compound classes could be increased with large N-substituents (e.g. 2-phenylethyl, octyl). Nevertheless the benzyl derivative 4a represents the most promising σ(1) ligand (K(i) = 25 nM) due to its high selectivity against the σ(2) subtype (>40-fold), the NMDA receptor and 5-HT(6) and 5-HT(7) receptors. Moreover, 4a did not inhibit the hERG channel in the heart.