title: The low affinity PCP sites in the rat cerebellum not only bind TCP-like but also BTCP-like structures.
abstract: Congeners of the potent dopamine (DA) re-uptake inhibitor 1-[1-(2-benzo[b]thiophenyl)cyclohexyl]piperidine (BTCP) are unexpectedly able to bind in the rat cerebellum, although this structure is devoid of dopaminergic nerve endings. In line with previous studies the hypothesis that they bind to low affinity PCP sites labelled with [3H]TCP in the rat cerebellum, even though they do not bind to the high affinity PCP sites in the forebrain, was considered. Analogues of 1-[1-(2-thiophenyl)cyclohexyl]piperidine (TCP) and BTCP with a modified aromatic moiety and with O or S atoms substituted in the cyclohexyl ring were prepared and tested in competition experiments both in rat forebrain and cerebellum membranes labelled with [3H]TCP, and in rat striatum membranes labelled with [3H]BTCP. Results indicated that BTCP and congeners could bind to low affinity PCP sites labelled with [3H]TCP in the rat cerebellum with a decrease of the selectivity for the DA transporter. On the contrary, some TCP analogues displayed a very high selectivity for these low affinity sites; they might be important pharmacological tools to elucidate the nature and function at yet unknown of these sites.
authors.affiliation: CRBM, CNRS UPR 1086, Ecole nationale supérieure de chimie, 8, rue de l'Ecole-normale, 34296, Montpellier, France.
authors.forename: F
authors.initials: F
authors.lastname: Espaze
authors.forename: J
authors.initials: J
authors.lastname: Hamon
authors.forename: H
authors.initials: H
authors.lastname: Hirbec
authors.forename: J
authors.initials: J
authors.lastname: Vignon
authors.forename: J M
authors.initials: JM
authors.lastname: Kamenka
mesh_terms: D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism*; D016291:Dizocilpine Maleate / Q000378:metabolism; D018491:Dopamine Agonists / Q000378:metabolism*; D018691:Excitatory Amino Acid Antagonists / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D017072:Neostriatum / Q000187:drug effects / Q000378:metabolism; D010622:Phencyclidine / Q000031:analogs & derivatives* / Q000378:metabolism*; D016548:Prosencephalon / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D017478:Receptors, Phencyclidine / Q000187:drug effects / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D018491:Dopamine Agonists; D018691:Excitatory Amino Acid Antagonists; D017478:Receptors, Phencyclidine; C056415:1-(1-(2-benzo(b)thienyl)cyclohexyl)piperidine; D016291:Dizocilpine Maleate; C012058:tenocyclidine; D010622:Phencyclidine