D-4 DOPAMINE-RECEPTOR BINDING-AFFINITY DOES NOT DISTINGUISH BETWEEN TYPICAL AND ATYPICAL ANTIPSYCHOTIC-DRUGS

The affinities of 13 atypical and 12 typical antipsychotic drugs for the cloned rat D-4 dopamine receptor and the D-4/D-2 ratios were examined. Of the atypical antipsychotic drugs tested, only clozapine, risperidone, olanzapine, zotepine and tiospirone had affinities less than 20 nM. In fact, many atypical antipsychotic drugs had relatively low affinities for the cloned rat D-4 receptor, with Ki values greater than 100 nM (Seroquel, fluperlapine, tenilapine, FG5803 and melperone). Additionally, several typical antipsychotic drugs had high affinities for the cloned rat D-4 receptor, with K(i)s less than 20 nM (loxapine, chlorpromazine, fluphenazine, mesoridazine, thioridazine and trifluoroperazine). The ratios of D-2/D-4 affinities did not differentiate between these two types of antipsychotic drugs. Thus, D-4 dopamine receptor affinity, used as a single measure, does not distinguish between the group of typical and atypical antipsychotic drugs analyzed.