Lever J R, Scheffel U A, Stathis M, Musachio J L, Wagner H N
Department of Environmental Health Sciences, Johns Hopkins University, Baltimore, Maryland 21205.
Life Sci. 1990;46(26):1967-76. doi: 10.1016/0024-3205(90)90513-q.
Apparent affinities (Ki) 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 (Ki 0.35 nM, D2; Ki 1.75 nM, 5-HT2) proved slightly more potent and selective for D2 sites in vitro than (E)-NIASP (Ki 0.72 nM, D2; Ki 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, alpha 1-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.
在竞争结合试验中测定了（E）-和（Z）-N-（碘烯丙基）螺哌隆[（E）-和（Z）-NIASP]对多巴胺D2和5-羟色胺5-HT2受体的表观亲和力（Ki）。（Z）-NIASP（Ki为0.35 nM，D2；Ki为1.75 nM，5-HT2）在体外对D2位点的效力和选择性略高于（E）-NIASP（Ki为0.72 nM，D2；Ki为1.14 nM，5-HT2）。在体内，放射性碘化的（E）-和（Z）-[125I]-NIASP在小鼠脑中显示出区域分布，这与多巴胺D2受体的长时间结合以及持续时间较短的次要血清素能成分一致。发现与多巴胺D2位点结合的药物对（E）-[125I]-NIASP摄取具有立体选择性、剂量依赖性阻断作用，而对5-羟色胺5-HT2、α1-肾上腺素能和多巴胺D1受体具有选择性的药物在注射后2小时不抑制放射性配体结合。在研究的时间过程中，纹状体组织中的特异性结合基本上是不可逆的，注射后6小时，（E）-[125I]-NIASP的纹状体与小脑组织放射性浓度比为16.9比1。因此，（E）-[125I]-NIASP在体内与多巴胺D2位点具有高选择性和特异性结合。
