A comparison of the binding of σ opioids and phencyclidine, and the interaction with antipsychotic drugs in rat brain membranes

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Abstract
1 The present study investigates the relationship between binding at the s̀ site labelled by the prototypic s̀ ligand (+)-[3H]-N-allylnormetazocine ((+)-[3H]-SKF10,047) and binding at the phencyclidine (PCP) site labelled by [3H]-phencyclidine in rat whole brain membranes. 2 (+)-[3H]-SKF10,047 bound with a KD of 251 ± 66 nM. [3H]-PCP bound with a KD of 180 ± 35 nM (KD ± asymptotic s.e.). 3 The potencies of a range of compounds to displace these ligands were only poorly correlated (r = 0.3). Furthermore selective displacement of (+)-[3H]-SKF10,047 but not of [3H]-PCP was demonstrated using the non-selective dopamine ligand haloperidol and the dopamine2-selective ligand 3-(3-hydroxyphenyl)N-n-propylpiperidine (3PPP). These results indicate that the s̀ and PCP sites are different entities. 4 The relationship between binding at the s̀ site and dopamine receptors was investigated in rat whole brain membranes and in striatal membranes. 5 (±)-SKF10,047 displaced [3H]-haloperidol bound to whole brain membranes with a greater potency than it displaced [3H]-haloperidol bound to striatal membranes. The opposite was true for the dopamine antagonist, clozapine, which showed greater potency in striatal membranes. 6 Comparison of [3H]-haloperidol binding in whole brain and striatum gave only a poor correlation (r = 0.6). Hence, different binding sites would appear to exist in these brain regions, the binding of [3H]-haloperidol to whole brain being predominantly to s̀ sites and the binding to striatum being predominantly to dopamine receptors.
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