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 t he cloned rat D-4 dopamine receptor and the D-4/D-2 ratios were examin ed. Of the atypical antipsychotic drugs tested, only clozapine, risper idone, olanzapine, zotepine and tiospirone had affinities less than 20 nM. In fact, many atypical antipsychotic drugs had relatively low aff inities for the cloned rat D-4 receptor, with Ki values greater than 1 00 nM (Seroquel, fluperlapine, tenilapine, FG5803 and melperone). Addi tionally, several typical antipsychotic drugs had high affinities for the cloned rat D-4 receptor, with K(i)s less than 20 nM (loxapine, chl orpromazine, fluphenazine, mesoridazine, thioridazine and trifluoroper azine). The ratios of D-2/D-4 affinities did not differentiate between these two types of antipsychotic drugs. Thus, D-4 dopamine receptor a ffinity, used as a single measure, does not distinguish between the gr oup of typical and atypical antipsychotic drugs analyzed.