Striatal D2-dopamine receptor occupancy during treatment with typical and atypical neuroleptics

Abstract

Dopamine D2 receptors can be studied in vivo using Posiuon Emission Tomography (PET) and Single Photon Emission Computed Tomography (SPECT) technique applying the tracers CRaclopride and mIodobenz,onide (mI-IBZM). PET studies demonstrated selective effects of different neuroleptics (NLs) on D2 and DI dopamine receptor occupancy (Sedvall 1992). Farde et al (1989, 1992) reported that clozapine, an atypical neuroleptic (AN) shows a decreased D2 and increased D 1 receptor occupancy compared to typical neuroleptics (TN), such as haloperidol. The lower D2 receptor occupancy by clozapine could be replicated by SPECT technique (Briicke et al 1992). Because the amount of D2 receptor blockade is most likely related to the occurrence of extrapyramidal symptoms (EPMS) side effects (Farde et a11989,1992), it is of considerable interest to investigate whether there exists a different dose-response relation between striatal D2 receptor occupancy and total daily dosage of typical NLs compared to atypical NLs. So far, this has been done only once by SPECT technique (Briicke et al 1992), suggesting a curvilinear dose-response relation for'IN with no such relation for AN. These authors apparently investigated different'INs in a small number of patients, however, and evaluated the dose-response relationship of the different NLs on the basis of cMorpromazine equivalents, a procedure that reduces the accuracy of these data.