The relationship between the daily dose, the plasma concentration of blonanserin, and its plasma anti-dopamine D2 and anti-serotonin 5-HT2A activity.
OBJECTIVE
Blonanserin (BNS) possesses anti-serotonin 5-HT(2A) activity in addition to anti-dopamine D(2) activity, which is characteristic of second-generation antipsychotics, little information is available on its pharmacologic profile in vivo. We investigated the BNS daily dose, plasma concentration, plasma anti-D(2) activity, and plasma anti-5-HT(2A) activity in schizophrenia in a total of 14 subjects.


METHODS
Blood samples were taken 14 days after the BNS dose was fixed, and the plasma concentration was measured by means of high-performance liquid chromatographic (HPLC) method. In addition, the plasma anti-D(2) activity and anti-5-HT(2A) activity were measured by means of radioreceptor assays in which [(3)H]-spiperone and [(3)H]-ketanserin were used.


RESULTS
The results revealed a statistically significant correlation between the daily dose and the plasma concentration (p = 0.04). Statistically significant correlations were also observed between the plasma concentration and the anti-D(2) activity and between the plasma concentration and the anti-5-HT(2A) activity (p = 0.003 and 0.04).


CONCLUSIONS
It is therefore believed that both the anti-D(2) activity in plasma and the anti-5-HT(2A) activity in plasma are regulated almost solely by the unchanged principal. Moreover, the mean plasma serotonin/dopamine (S/D) ratio was 0.9 and BNS exhibited both anti-D(2) activity and also anti-5-HT(2A) activity in vivo, as well, so it was clear that the in vitro pharmacological profile was retained in vivo.
Suzuki
Hidenobu
H
Tanzawa Hospital, Hadano, Kanagawa, Japan. suzuhide@red.livedoor.com
Gen
Keishi
K
D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000008:administration & dosage* / Q000097:blood*; D001386:Azides / Q000008:administration & dosage / Q000097:blood; D001921:Brain / Q000187:drug effects; D018492:Dopamine Antagonists / Q000008:administration & dosage / Q000097:blood; D065127:Dopamine D2 Receptor Antagonists; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000008:administration & dosage* / Q000097:blood*; D010880:Piperidines / Q000008:administration & dosage* / Q000097:blood*; D011869:Radioligand Assay; D012701:Serotonin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000097:blood; D058830:Serotonin 5-HT2 Receptor Antagonists
D014150:Antipsychotic Agents; D001386:Azides; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D010879:Piperazines; D010880:Piperidines; D058830:Serotonin 5-HT2 Receptor Antagonists; D012701:Serotonin; C046122:3-(2-(4-azidobenzamidino)ethyl)-5-hydroxyindole; C079310:blonanserin