INTERACTIONS OF ERYTHRO-IFENPRODIL, THREO-IFENPRODIL, ERYTHRO-IODOIFENPRODIL, AND ELIPRODIL WITH SUBTYPES OF SIGMA-RECEPTORS

Observations of sigma (sigma) receptor heterogeneity have prompted interest in identifying ligands for sigma receptor subtypes. Selective ligands for the sigma-2 are unavailable, but [H-3]ifenprodil labels sigma-2 sites. Therefore, isomers and analogues of ifenprodil were compared as potential sigma-2 ligands. Threo-ifenprodil and erythro-ifenprodil had high affinity (K-i similar or equal to 2 nM) for sigma-2 sites; erythro-iodoifenprodil had moderate affinity (K-i similar or equal to 46 nM); eliprodil had lowest affinity (K-i similar or equal to 630 nM). Threo-ifenprodil, which has less affinity for alpha(1)-adrenoceptors than erythro-ifenprodil, was slightly more selective than erythro-ifenprodil for sigma-2 sites. These results identify threo-ifenprodil as potentially useful for studies of sigma-2 receptors.