F. Espaze et al., The low affinity PCP sites in the rat cerebellum not only bind TCP-like but also BTCP-like structures, EUR J MED C, 35(3), 2000, pp. 323-331
Congeners of the potent dopamine (DA) re-uptake inhibitor 1-[1-(2-benzo[b]t
hiophenyl)cyclohexyl]piperidine (BTCP) are unexpectedly able to bind in the
rat cerebellum although this structure is devoid of dopaminergic nerve end
ings. In line with previous studies the hypothesis that they bind to low af
finity PCP sites labelled with [H-3]TCP in the rat cerebellum, even though
they do not bind to the high affinity PCP sites in the forebrain, was consi
dered. 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 c
yclohexyl ring were prepared and tested in competition experiments both in
rat forebrain and cerebellum membranes labelled with [H-3]TCP, and in rat s
triatum membranes labelled with [H-3]BTCP. Results indicated that BTCP and
congeners could bind to low affinity PCP sites labelled with [H-3]TCP in th
e rat cerebellum with a decrease of the selectivity fur 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. (C) 2000 E
ditions scientifiques et medicales Elsevier SAS.