Dompert W U, Glaser T, Traber J
Naunyn Schmiedebergs Arch Pharmacol. 1985 Feb;328(4):467-70. doi: 10.1007/BF00692918.
In order to clarify the mechanism of action of the putative nonbenzodiazepine anxiolytic TVX Q 7821 [2-(4-(4-(2-pyrimidinyl)-1-piperazinyl)butyl)-1, 2-benzisothiazol-3-(2H)one-1,1-dioxidehydrochloride], binding studies with the radio labelled compound were performed. 3H-TVX Q 7821 bound rapidly, reversibly and in a saturable manner with high affinity to calf brain structures with preference for the hippocampus (KD 1.62 nmol/l; Bmax 320 fmol/ mg protein). 3H-TVX Q 7821 binding was displaced only by 5-hydroxytryptamine and its agonists and antagonists including spiperone, but was not displaced by a variety of other neurotransmitters and drugs. The 5-HT2 receptor antagonist ketanserin was a weak displacer. The hippocampal binding sites for 3H-TVX Q 7821 were pharmacologically very similar to the 5-HT1-binding sites in this region. TVX Q 7821 is likely to be an important tool in research on functional aspects of 5-HT1 binding sites.
为阐明假定的非苯二氮䓬类抗焦虑药TVX Q 7821[2-(4-(4-(2-嘧啶基)-1-哌嗪基)丁基)-1,2-苯并异噻唑-3-(2H)酮-1,1-二氧化物盐酸盐]的作用机制，进行了放射性标记化合物的结合研究。3H-TVX Q 7821能快速、可逆且以饱和方式与小牛脑结构高亲和力结合，对海马体有偏好性（解离常数KD为1.62纳摩尔/升；最大结合量Bmax为320飞摩尔/毫克蛋白）。3H-TVX Q 7821的结合仅被5-羟色胺及其激动剂和拮抗剂（包括螺哌隆）取代，但未被多种其他神经递质和药物取代。5-HT2受体拮抗剂酮色林是一种较弱的取代剂。3H-TVX Q 7821在海马体的结合位点在药理学上与该区域的5-HT1结合位点非常相似。TVX Q 7821可能是研究5-HT1结合位点功能方面的重要工具。
