[3H]N-[1-(2-benzo(b)thiophenyl)cyclohexyl]piperidine ([3H]BTCP): a new phencyclidine analog selective for the dopamine uptake complex.
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.
Vignon
J
J
CNRS LP 8402 (UM 1), INSERM U 249, Ecole Nationale Supérieure de Chimie, Montpellier, France.
Pinet
V
V
Cerruti
C
C
Kamenka
J M
JM
Chicheportiche
R
R
D000818:Animals; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D066298:In Vitro Techniques; D010622:Phencyclidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D013574:Synaptosomes / Q000378:metabolism; D014316:Tritium
D011954:Receptors, Dopamine; D014316:Tritium; C056415:1-(1-(2-benzo(b)thienyl)cyclohexyl)piperidine; D010622:Phencyclidine; D004298:Dopamine