Agonist-stimulated GTPγ[35S] binding to 5-HT1Areceptors in human post-mortem brain

In this study, we have demonstrated that the technique of agonist-stimulated guanosine-5'-O-(3-[ 35 S]thio)-triphosphate (GTPγ[ 35 S]) binding can be successfully used to study the functional activity of the human 5-HT 1A receptor in post-mortem tissue. Full agonist and antagonist actions of ligands specific for this site have been shown. Utilising 4-(2'-methoxy-phenyl)-1-[2'-(n-2-pyridinyl)-p-fluorobenzamido]-ethyl-piperazine ([ 3 H]MPPF), the affinity of several antipsychotics for the 5-HT 1A receptor was determined; clozapine and quetiapine were found to have K i values at this receptor that, relative to their dopamine D 2 receptor affinities, indicated at least partial receptor occupancy at clinical doses. The agonist/antagonist activity of these two antipsychotics was studied using GTPγ[ 35 S] binding. Both compounds show partial agonism, and in addition, clozapine exhibited a larger degree of antagonism against 5-HT-stimulated binding than did quetiapine.