Vignon J, Pinet V, Cerruti C, Kamenka J M, Chicheportiche R
CNRS LP 8402 (UM 1), INSERM U 249, Ecole Nationale Supérieure de Chimie, Montpellier, France.
Eur J Pharmacol. 1988 Apr 13;148(3):427-36. doi: 10.1016/0014-2999(88)90122-7.
A benzothiophenyl group instead of a phenyl ring on phencyclidine (PCP) yields a molecule N-[1-(2-benzo(b)thiophenyl)cyclohexyl]piperidine (BTCP), which is one of the more potent known dopamine (DA) uptake inhibitors (IC50 = 7 nM). This compound also has low affinity for the PCP receptor (K0.5 = 6 microM). The sodium-dependent [3H]BTCP binding to rat striatal membranes was investigated. [3H]BTCP bound to two different sites: one with very high affinity (Kd1 = 0.9 nM, Bmax1 = 3.5 pmol/mg protein) which paralleled the distribution of dopaminergic nerve endings and a second with lower affinity (Kd2 = 20 nM, Bmax2 = 7.5 pmol/mg protein). There was a good correlation between the abilities of drugs specific for the DA uptake complex and of PCP analogs to inhibit high affinity [3H]BTCP binding and [3H]DA synaptosomal uptake. This study also demonstrated that PCP interacts with the DA uptake site since it is a competitive inhibitor of high affinity [3H]BTCP binding. This site, however, is not the PCP receptor, which has a different pharmacological selectivity.
在苯环己哌啶（PCP）上用苯并噻吩基取代苯环可得到一种分子N-[1-(2-苯并(b)噻吩基)环己基]哌啶（BTCP），它是已知的效力较强的多巴胺（DA）摄取抑制剂之一（IC50 = 7 nM）。该化合物对PCP受体的亲和力也较低（K0.5 = 6 microM）。研究了钠依赖性的[3H]BTCP与大鼠纹状体膜的结合。[3H]BTCP与两个不同的位点结合：一个具有非常高的亲和力（Kd1 = 0.9 nM，Bmax1 = 3.5 pmol/mg蛋白质），这与多巴胺能神经末梢的分布平行，另一个具有较低的亲和力（Kd2 = 20 nM，Bmax2 = 7.5 pmol/mg蛋白质）。对DA摄取复合物具有特异性的药物和PCP类似物抑制高亲和力[3H]BTCP结合及[3H]DA突触体摄取的能力之间存在良好的相关性。该研究还表明PCP与DA摄取位点相互作用，因为它是高亲和力[3H]BTCP结合的竞争性抑制剂。然而，这个位点不是PCP受体，PCP受体具有不同的药理学选择性。
