Effects of the antipsychotic risperidone on dopamine synthesis in human brain measured by positron emission tomography with L-[beta-11C]DOPA: a stabilizing effect for dopaminergic neurotransmission?

J Neurosci. 2009 Oct 28;29(43):13730-4. doi: 10.1523/JNEUROSCI.4172-09.2009.

Abstract

Effects of antipsychotic drugs have widely been considered to be mediated by blockade of postsynaptic dopamine D(2) receptors. Effects of antipsychotics on presynaptic functions of dopaminergic neurotransmission might also be related to therapeutic effects of antipsychotics. To investigate the effects of antipsychotics on presynaptic functions of dopaminergic neurotransmission in relation with occupancy of dopamine D(2) receptors, changes in dopamine synthesis capacity by antipsychotics and occupancy of dopamine D(2) receptors were measured by positron emission tomography (PET) in healthy men. PET studies using [(11)C]raclopride and L-[beta-(11)C]DOPA were performed under resting condition and oral administration of single dose of the antipsychotic drug risperidone on separate days. Although occupancy of dopamine D(2) receptors corresponding dose of risperidone was observed, the changes in dopamine synthesis capacity by the administration of risperidone were not significant, nor was the relation between the occupancy of dopamine D(2) receptors and these changes. A significant negative correlation was observed between the baseline dopamine synthesis capacity and the changes in dopamine synthesis capacity by risperidone, indicating that this antipsychotic can be assumed to stabilize the dopamine synthesis capacity. The therapeutic effects of risperidone in schizophrenia might be related to such stabilizing effects on dopaminergic neurotransmission responsivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antipsychotic Agents / administration & dosage
  • Antipsychotic Agents / blood
  • Antipsychotic Agents / pharmacology*
  • Brain / diagnostic imaging
  • Brain / drug effects*
  • Brain / physiology*
  • Carbon Radioisotopes
  • Caudate Nucleus / diagnostic imaging
  • Caudate Nucleus / drug effects
  • Caudate Nucleus / physiology
  • Dopamine / biosynthesis
  • Dopamine / metabolism*
  • Dose-Response Relationship, Drug
  • Humans
  • Isoxazoles / blood
  • Isoxazoles / pharmacology
  • Levodopa
  • Male
  • Paliperidone Palmitate
  • Positron-Emission Tomography
  • Putamen / diagnostic imaging
  • Putamen / drug effects
  • Putamen / physiology
  • Pyrimidines / blood
  • Pyrimidines / pharmacology
  • Raclopride
  • Receptors, Dopamine D2 / metabolism
  • Rest / physiology
  • Risperidone / administration & dosage
  • Risperidone / blood
  • Risperidone / pharmacology*
  • Synaptic Transmission / physiology*
  • Young Adult

Substances

  • Antipsychotic Agents
  • Carbon Radioisotopes
  • Isoxazoles
  • Pyrimidines
  • Receptors, Dopamine D2
  • Raclopride
  • Levodopa
  • Risperidone
  • Paliperidone Palmitate
  • Dopamine