Time course of dopamine-D2 and serotonin-5-HT2 receptor occupancy rates by haloperidol and clozapine in vivo.
In vivo occupancy of dopamine-D1, D2 and serotonin-5-HT2 receptors by haloperidol 10 mg/kg and clozapine 20 mg/kg were studied. Rats were injected intravenously with [3H]-YM-09151-2, [3H]-SCH23390, or [3H]-ketanserin 10 min after the administration of the tested drugs. Fifteen to 240 min after the ligand injection, the receptor occupancy rates of the drugs in the striatum and frontal cortex were calculated. Clozapine demonstrated the higher 5-HT2 and lower D2 occupancies in the respective regions. A dose-response analysis of D2 and 5-HT2 receptor occupancy by the drugs consolidated the higher 5-HT2 binding affinity of clozapine in comparison with haloperidol. The present methodology may serve as an accurate tool to evaluate the peculiarity of various antipsychotics.
Sumiyoshi
T
T
Department of Neuropsychiatry, Kanazawa University School of Medicine, Japan.
Kido
H
H
Sakamoto
H
H
Urasaki
K
K
Suzuki
K
K
Yamaguchi
N
N
Mori
H
H
Shiba
K
K
Yokogawa
K
K
Ichimura
F
F
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D003024:Clozapine / Q000378:metabolism* / Q000494:pharmacology; D006220:Haloperidol / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*; D013997:Time Factors
D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin; D003024:Clozapine; D006220:Haloperidol