Dose determination of haloperidol, risperidone and olanzapine using an in vivo dopamine D2-receptor occupancy method in the rat.
The purpose of the present study was to determine antipsychotic doses that achieve 80% striatal dopamine D2-receptor occupancy for haloperidol, risperidone and olanzapine in rats. Wistar rats were treated with normal saline vehicle (controls), haloperidol (0.25 and 0.5 mg/kg/day), risperidone (3, 5 and 6 mg/kg/day) and olanzapine (5 and 10 mg/kg/day) for 7 days via osmotic minipumps. Striatal and cerebellar tissue were collected and in vivo dopamine D2-receptor occupancies were determined using 3H-raclopride. The doses required to achieve dopamine D2-receptor occupancy of 80% in 11- and 24-week old rats were: haloperidol 0.25 mg/kg/day, risperidone 5 mg/kg/day and olanzapine 10 mg/kg/day.
Naiker
Dineshree V
DV
School of Medicine, The University of Queensland, Brisbane QLD 4072 Australia.
Catts
Stanley V
SV
Catts
Vibeke S
VS
Bedi
Kuldip S
KS
Bryan-Lluka
Lesley J
LJ
D000465:Algorithms; D000704:Analysis of Variance; D000818:Animals; D014150:Antipsychotic Agents / Q000008:administration & dosage; D001569:Benzodiazepines / Q000008:administration & dosage; D001667:Binding, Competitive / Q000187:drug effects; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D006220:Haloperidol / Q000008:administration & dosage*; D008297:Male; D000077152:Olanzapine; D020891:Raclopride / Q000378:metabolism; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000378:metabolism*; D018967:Risperidone / Q000008:administration & dosage*; D014316:Tritium
D014150:Antipsychotic Agents; D017448:Receptors, Dopamine D2; D014316:Tritium; D001569:Benzodiazepines; D020891:Raclopride; D006220:Haloperidol; D018967:Risperidone; D000077152:Olanzapine