In vitro and in vivo binding of (E)- and (Z)-N-(iodoallyl)spiperone to dopamine D₂ and serotonin 5-HT₂ neuroreceptors

Apparent affinities (K_i) of (E)- and (Z)-N-(iodoallyl)spiperone ((E)- and (Z)-NIASP) for dopamine D₂ and serotonin 5-HT₂ receptors were determined in competition binding assays. (Z)-NIASP (K_i 0.35 nM, D₂; K_i 1.75 nM, 5-HT₂) proved slightly more potent and selective for D₂ sites in vitro than (E)-NIASP (K_i 0.72 nM, D₂; K_i 1.14 nM, 5-HT₂). In vivo, radioiodinated (E)- and (Z)-[¹²⁵I]-NIASP showed regional distributions in mouse brain which are consonant with prolonged binding to dopamine D₂ receptors accompanied by a minor serotonergic component of shorter duration. Stereoselective, dose-dependent blockade of (E)-[¹²⁵I]-NIASP uptake was found for drugs binding to dopamine D₂ sites, while drugs selective for serotonin 5-HT₂, α1- adrenergic and dopamine D₁ receptors did not inhibit radioligand binding 2 hr postinjection. Specific binding in striatal tissue was essentially irreversible over the time course of the study, and (E)-[¹²⁵I]-NIASP gave a striatal to cerebellar tissue radioactivity concentration of 16.9 to 1 at 6 hr postinjection. Thus, (E)-[¹²⁵I]-NIASP binds with high selectivity and specificity to dopamine D₂ sites in vivo.