1‐(Arylalkyl)quinolizidine Derivatives and Thio‐Isosteric Analogues as Ligands for Sigma Receptors

A set of 1‐(arylalkyl)quinolizidines, isosteric thioanalogues, and variously functionalized congeners were synthesized (see 1 – 25 ) and tested for affinity to sigma 1 and sigma 2 receptor subtypes, by displacing [³H]‐ (+)‐pentazocine and [³H]DTG from guinea pig brain and rat brain preparations, respectively. All compounds exhibited a good affinity for the σ₁ subtype, with subnanomolar K_i values for the best of them, while only modest or poor affinity for the σ₂ subtype was observed (Tables 1 and 2). Some structure? activity relationships were put forward.