Format

Send to

Choose Destination
See comment in PubMed Commons below
Neuropsychopharmacology. 2001 Oct;25(4):476-88.

Evaluation of dopamine D-2 receptor occupancy by clozapine, risperidone, and haloperidol in vivo in the rodent and nonhuman primate brain using 18F-fallypride.

Author information

1
Department of Internal Medicine/Nuclear Medicine, Kettering Medical Center, Wright State University, Dayton, OH, USA. mukherjj@uci.edu

Abstract

We have used the high-affinity dopamine D-2 receptor radioligand, 18F-fallypride for evaluating receptor occupancy by the antipsychotic drugs, clozapine, risperidone, and haloperidol in rodents and nonhuman primates. In rodents, clozapine (0.1 mg/kg to 100 mg/kg) competed with 18F-fallypride at all the doses administered. At doses over 40 mg/kg, clozapine was able to displace all the administered 18F-fallypride. A pseudobiphasic profile of receptor occupancy by clozapine was observed. This behavior was compared with such other neuroleptics as risperidone and haloperidol that exhibited over 90% receptor occupancy at doses over 0.1 mg/kg and did not exhibit a biphasic nature. Dopamine D-2 receptor occupancy in the monkeys was studied using positron emission tomography (PET) after acute subcutaneous doses of the various drugs. At therapeutically relevant doses, clozapine, risperidone, and haloperidol were able to compete significantly with the binding of 18F-fallypride in all brain regions in rhesus monkeys, and our analyses indicate that these drugs (clozapine, risperidone, and haloperidol) do not discriminate between the striatal (caudate and putamen) and the extrastriatal (thalamus and cortical regions) dopamine receptors. The following extent of D-2 receptor occupancies were measured in the monkey brain using PET: clozapine approximately 70% (dose of 9.7 mg/kg), risperidone approximately 75% (0.05 mg/kg), and haloperidol approximately 90% (0.05 mg/kg).

PMID:
11557161
DOI:
10.1016/S0893-133X(01)00251-2
[Indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Nature Publishing Group
    Loading ...
    Support Center