Dopamine D2 receptor blockade in vivo with the novel antipsychotics risperidone and remoxipride--an 123I-IBZM single photon emission tomography (SPET) study.
Risperidone and remoxipride are recently introduced atypical antipsychotics, with clinical efficacy comparable to that of classical antipsychotics but lower propensity to induce extrapyramidal side effects (EPS). It is unclear whether these properties relate to weak dopamine D2 receptor blockade in vivo, as has been suggested for the archetypal atypical antipsychotic clozapine. We have used 123I-IBZM single photon emission tomography (SPET) to characterize the patterns of striatal D2 receptor binding in vivo in DSMIII-R-diagnosed schizophrenic and schizo-affective patients treated with either risperidone (n = 6) or remoxipride (n = 4) but predominantly EPS free. These groups were compared to age- and BPRS- matched subjects from a previously reported D2 receptor binding database of patients treated with clozapine (n = 10) and classical antipsychotics (n = 10). Patients on risperidone and remoxipride had high levels of D2 receptor blockade, comparable to those of patients on classical antipsychotics, and significantly greater than those obtained with clozapine-treated patients (risperidone versus clozapine, P < 0.005; remoxipride versus clozapine, P < 0.025). These results suggest high levels of striatal D2 receptor occupancy in association with remoxipride and risperidone treatment and argue against modest D2 antagonism as the explanation for the low incidence of EPS associated with these drugs.
Busatto
G F
GF
Department of Psychological Medicine, Institute of Psychiatry, Denmark Hill, London, UK.
Pilowsky
L S
LS
Costa
D C
DC
Ell
P J
PJ
Verhoeff
N P
NP
Kerwin
R W
RW
D000328:Adult; D014150:Antipsychotic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001479:Basal Ganglia / Q000378:metabolism; D001549:Benzamides; D002540:Cerebral Cortex / Q000378:metabolism; D065127:Dopamine D2 Receptor Antagonists; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007457:Iodine Radioisotopes; D007555:Isoxazoles / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D017072:Neostriatum / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology* / Q000627:therapeutic use; D011569:Psychiatric Status Rating Scales; D011618:Psychotic Disorders / Q000188:drug therapy / Q000378:metabolism; D011759:Pyrrolidines; D017330:Remoxipride / Q000494:pharmacology* / Q000627:therapeutic use; D018967:Risperidone; D012559:Schizophrenia / Q000188:drug therapy / Q000378:metabolism; D015899:Tomography, Emission-Computed, Single-Photon
D014150:Antipsychotic Agents; D001549:Benzamides; D065127:Dopamine D2 Receptor Antagonists; D007457:Iodine Radioisotopes; D007555:Isoxazoles; D010880:Piperidines; D011759:Pyrrolidines; D017330:Remoxipride; C055743:3-iodo-2-hydroxy-6-methoxy-N-((1-ethyl-2-pyrrolidinyl)methyl)benzamide; D018967:Risperidone