Long-term perospirone treatment with a single dose at bedtime in schizophrenia: relevant to intermittent dopamine D2 receptor antagonism

Prog Neuropsychopharmacol Biol Psychiatry. 2008 Feb 15;32(2):520-2. doi: 10.1016/j.pnpbp.2007.10.008. Epub 2007 Oct 22.

Abstract

Perospirone, a serotonin 5-HT2A and dopamine D2 receptor antagonist, is metabolized to ID-15036 by CYP3A4 and the elimination half-life (T1/2) for the latter is longer than the former. The active metabolite ID-15036 is an 8-times weaker D2 antagonist than perospirone, although it has a high affinity for 5-HT2A receptor. In this study, we measured the plasma concentrations of perospirone and ID-15036 in the long-term stable schizophrenic patients with a single dose of perospirone at bedtime. The mean level of perospirone at 11-15 h after a last dosing was much lower (0.49 ng/ml) than that of ID-15036 (2.89 ng/ml). These results show that a long-term perospirone monotherapy with a single dose at bedtime is effective for the maintenance treatment of chronic schizophrenia and also suggest the possibility that intermittent D2 receptor blockade may be sufficient for effective relapse prevention.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Ambulatory Care
  • Antipsychotic Agents / blood
  • Antipsychotic Agents / pharmacology
  • Antipsychotic Agents / therapeutic use*
  • Chromatography, High Pressure Liquid
  • Dopamine D2 Receptor Antagonists*
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Female
  • Follow-Up Studies
  • Humans
  • Indoles / blood
  • Isoindoles / blood
  • Isoindoles / pharmacology
  • Isoindoles / therapeutic use*
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Schizophrenia / drug therapy*
  • Schizophrenic Psychology
  • Secondary Prevention
  • Thiazoles / blood
  • Thiazoles / pharmacology
  • Thiazoles / therapeutic use*
  • Treatment Outcome

Substances

  • Antipsychotic Agents
  • Dopamine D2 Receptor Antagonists
  • Indoles
  • Isoindoles
  • Thiazoles
  • hydroxyperospirone
  • perospirone