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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 sigma1 subtype, with subnanomolar Ki values for the best of them, while only modest or poor affinity for the sigma2 subtype was observed (Tables 1 and 2). Some structure-activity relationships were put forward.
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