The relationship between the daily dose, the plasma concentration of blonanserin, and its plasma anti-dopamine D2 and anti-serotonin 5-HT2A activity

• Published in: Human psychopharmacology Vol. 25; no. 4; pp. 342 - 346
• Main Authors: Suzuki, Hidenobu, Gen, Keishi
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 01.06.2010
• Subjects: Adult; Aged; anti-dopamine D2 activity; anti-serotonin 5-HT2A activity; Antipsychotic Agents - administration & dosage; Antipsychotic Agents - blood; Azides - administration & dosage; Azides - blood; blonanserin; Brain - drug effects; Dopamine Antagonists - administration & dosage; Dopamine Antagonists - blood; Dopamine D2 Receptor Antagonists; Female; Humans; Male; Middle Aged; Piperazines - administration & dosage; Piperazines - blood; Piperidines - administration & dosage; Piperidines - blood; plasma concentration; Radioligand Assay; radioreceptor assay; Serotonin - administration & dosage; Serotonin - analogs & derivatives; Serotonin - blood; Serotonin 5-HT2 Receptor Antagonists
• ISSN: 0885-6222; 1099-1077; 1099-1077
• DOI: 10.1002/hup.1124

Objective Blonanserin (BNS) possesses anti‐serotonin 5‐HT2A activity in addition to anti‐dopamine D2 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‐D2 activity, and plasma anti‐5‐HT2A 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‐D2 activity and anti‐5‐HT2A activity were measured by means of radioreceptor assays in which [3H]‐spiperone and [3H]‐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‐D2 activity and between the plasma concentration and the anti‐5‐HT2A activity (p = 0.003 and 0.04). Conclusions It is therefore believed that both the anti‐D2 activity in plasma and the anti‐5‐HT2A 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‐D2 activity and also anti‐5‐HT2A activity in vivo, as well, so it was clear that the in vitro pharmacological profile was retained in vivo. Copyright © 2010 John Wiley & Sons, Ltd.