In vivo occupation of dopamine D1, D2 and serotonin (5-HT)2A receptors by sertindole in the rat brain.
OBJECTIVE
To determine the in vivo occupation of dopamine D1, D2 and serotonin (5-HT)2A receptors by novel antipsychotic agent sertindole using N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ), an irreversible antagonist at these receptor sites.


METHODS
Animal study.


METHODS
Intraperitoneal administration to Wistar rats of 1 of 4 test compounds: a control compound of 0.15% tartaric acid, or a compound of either sertindole (0.5 mg/kg or 2.0 mg/kg) or clozapine (20 mg/kg) dissolved in 0.15% tartaric acid 1 hour before intraperitoneal administration of EEDQ (8 mg/kg) or ethanol/water solution.


RESULTS
Sertindole exhibited little or no effect on D1 and D2 binding sites in vivo. On the other hand, sertindole occupied 5-HT2A receptors more extensively and firmly than EEDQ. This study indicates that sertindole is characterized by high occupancy of 5-HT2A receptors and by low or minimum occupancy of D1 and D2 receptors.


CONCLUSIONS
These characteristics are very similar to atypical antipsychotic agents such as clozapine. Sertindole's low liability to cause extrapyramidal side effects (EPS) may be related to greater long-term binding for 5-HT2A receptors relative to D2 receptors.
Takahashi
Y
Y
Department of Psychiatry, Hokkaido University School of Medicine, Sapporo, Japan. yoshito@med.hokudai.ac.jp
Kusumi
I
I
Ishikane
T
T
Matsubara
S
S
Koyama
T
T
D000818:Animals; D014150:Antipsychotic Agents / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects*; D007093:Imidazoles / Q000378:metabolism*; D007211:Indoles / Q000378:metabolism*; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D017208:Rats, Wistar; D017447:Receptors, Dopamine D1 / Q000187:drug effects / Q000378:metabolism*; D017448:Receptors, Dopamine D2 / Q000187:drug effects / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000378:metabolism*
D014150:Antipsychotic Agents; D007093:Imidazoles; D007211:Indoles; D017447:Receptors, Dopamine D1; D017448:Receptors, Dopamine D2; D011985:Receptors, Serotonin; C066304:sertindole