EFFECT OF LOWERED LIPOPHILICITY ON THE AFFINITY OF PCP ANALOGS FOR THE PCP RECEPTOR AND THE DOPAMINE TRANSPORTER

Oxygen and sulphur atoms were introduced in the cyclohexyl and piperid inyl moieties of the basic structures 1-(1-phenylcyclohexyl)piperidine (PCP), 1-[1-(2-thienyl)cyclohexyl]piperidine (TCP), and 1-[1-(2-benzo [b]thiophenyl)cyclohexyl]pi (BTCP) to lower their global lipophilicity . The compounds obtained were tested comparatively for their affinity for the PCP receptor labelled with [H-3]TCP and for the dopamine (DA) transporter labelled with [H-3]BTCP. Lowering the global lipophilicity in PCP and TCP series is detrimental to the affinity and selectivity for the PCP receptor. In the BTCP series lowering of the global lipoph ilicity is less deleterious and may, on the contrary, be a useful way of increasing selectivity for the DA transporter in some instances.