Billings J, Kung M P, Chumpradit S, Pan S, Kung H F
Department of Radiology, University of Pennsylvania, Philadelphia 19104.
Life Sci. 1989;45(8):711-8. doi: 10.1016/0024-3205(89)90090-8.
Radiolabeling and in vitro and in vivo evaluation of an iodinated benzazepine: [125I] FISCH 7-Chloro-8-hydroxy-1-(4'-iodophenyl)-3-methyl-2,3,4,5- tetrahydro-1H-3-benzazepine, as a potential imaging agent for CNS D-1 dopamine receptors in animals, were investigated. After an iv injection, this benzazepine derivative showed good brain uptake in rats (2.70, 1.28, 0.48 %dose/whole brain at 2, 15 and 60 min, respectively). The striatum/cerebellum ratio was 2.50 at 60 min after the injection. The regional distribution in rat brain, as measured by ex vivo autoradiography, displayed highest uptake in the regions of the striatal complex and the substantia nigra, regions known to have a high concentration of D-1 dopamine receptors. Furthermore, this localized regional cerebral distribution was blocked by pretreatment with SCH-23390, a selective D-1 dopamine receptor antagonist. The in vitro binding affinity of this agent in rat striatum tissue preparation displayed a Kd of 1.43 +/- 0.15 nM. Competition data (in vitro) showed the following rank order of potency: SCH-23390 greater than (+/-)IBZP much greater than apomorphine greater than WB 4101 greater than ketanserin approximately spiperone. The preliminary data suggest that this analog of SCH-23390 shows similar selectivity for the CNS D-1 receptor.
[125I]FISCH 7-氯-8-羟基-1-(4'-碘苯基)-3-甲基-2,3,4,5-四氢-1H-3-苯并氮杂卓作为动物中枢神经系统D-1多巴胺受体的潜在成像剂进行了研究。静脉注射后，这种苯并氮杂卓衍生物在大鼠体内显示出良好的脑摄取（分别在2、15和60分钟时为2.70、1.28、0.48%剂量/全脑）。注射后60分钟时纹状体/小脑比值为2.50。通过离体放射自显影测量的大鼠脑内区域分布显示，纹状体复合体和黑质区域摄取最高，已知这些区域D-1多巴胺受体浓度高。此外，这种局部脑区域分布被选择性D-1多巴胺受体拮抗剂SCH-23390预处理所阻断。该试剂在大鼠纹状体组织制备中的体外结合亲和力显示Kd为1.43±0.15 nM。竞争数据（体外）显示以下效价顺序：SCH-23390＞(±)IBZP＞阿扑吗啡＞WB 4101＞酮色林≈螺哌隆。初步数据表明，这种SCH-23390类似物对中枢神经系统D-1受体显示出相似的选择性。
