Differential interaction of phencyclidine-like drugs with the dopamine uptake complex in vivo.
The phencyclidine (PCP) derivative, [3H]N-[1-(2-benzo[b]thiophenyl)cyclohexyl]piperidine ([3H]BTCP), was used to label in vivo the dopamine uptake complex in mouse brain. The striatum accumulated the highest level of total and specific binding. Drugs which bind to the dopamine uptake site inhibited [3H]BTCP binding on an order similar to their in vitro affinities for the high-affinity [3H]BTCP site. Drugs which label selectively other monoamine uptake complexes. PCP, or sigma recognition sites were ineffective at doses up to 40 mg/kg. PCP bound to and dissociated from the dopamine uptake complex very rapidly. N-[1-(2-Thienyl)cyclohexyl]pideridine (TCP) and (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801) had no effect at any time or at any dose. These results imply that the pharmacological effects of PCP are due to its simultaneous interaction with the dopamine uptake complex and the PCP receptor. Conversely, TCP and MK-801, which have the same behavioral properties as PCP, exert their action only through the interaction with the PCP receptor.
Maurice
T
T
CNRS UPR 8402 INSERM U, 249 (UM 1), Ecole Nationale Supérieure de Chimie de Montpellier, France.
Vignon
J
J
Kamenka
J M
JM
Chicheportiche
R
R
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism*; D015259:Dopamine Agents / Q000378:metabolism* / Q000494:pharmacology; D050483:Dopamine Plasma Membrane Transport Proteins; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009627:Nomifensine / Q000494:pharmacology; D010622:Phencyclidine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology
D015259:Dopamine Agents; D050483:Dopamine Plasma Membrane Transport Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D010879:Piperazines; C056415:1-(1-(2-benzo(b)thienyl)cyclohexyl)piperidine; D009627:Nomifensine; C039737:1-(2-(diphenylmethoxy)ethyl)-4-(3-phenyl-2-propenyl)piperazine; D010622:Phencyclidine; D004298:Dopamine