Binding of a tritiated inverse agonist to cannabinoid CB1 receptors is increased in patients with schizophrenia

Schizophr Res. 2012 Nov;141(2-3):185-8. doi: 10.1016/j.schres.2012.07.021. Epub 2012 Aug 19.

Abstract

This study sought to determine whether cannabinoid-1 (CB(1)) receptor binding was altered in the postmortem dorsolateral prefrontal cortex (DLPFC) of individuals with schizophrenia (schizophrenia; n=47) compared to controls (n=43). The CB(1) receptor inverse agonist radioligand [(3)H]MePPEP was used to measure specific binding to CB(1) receptors. The specific binding of [(3)H]MePPEP to CB(1) receptors was 20% higher in patients with schizophrenia than in controls. Power analyses suggested that 53 subjects per group would be needed to detect a similar difference in vivo with positron emission tomography (PET) and the structurally related inverse agonist radioligand [(18)F]FMPEP-d(2) (80% statistical power, p<0.05).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adult
  • Aged
  • Cohort Studies
  • Female
  • Fluorine Radioisotopes / pharmacokinetics
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics
  • Positron-Emission Tomography
  • Prefrontal Cortex / diagnostic imaging*
  • Prefrontal Cortex / drug effects
  • Protein Binding / drug effects
  • Pyrrolidinones / pharmacokinetics
  • Receptor, Cannabinoid, CB1 / genetics
  • Receptor, Cannabinoid, CB1 / metabolism*
  • Regression Analysis
  • Schizophrenia / diagnostic imaging*
  • Schizophrenia / genetics
  • Schizophrenia / pathology*
  • Tissue Distribution / drug effects
  • Tritium / pharmacokinetics

Substances

  • 5-((3-fluoromethoxy)phenyl)-3-(1-phenylethylamino)-1-(4-trifluoromethylphenyl)pyrrolidin-2-one
  • 5-(3-methoxyphenyl)-3-(1-phenylethylamino)-1-(4-trifluoromethylphenyl)pyrrolidin-2-one
  • CNR1 protein, human
  • Fluorine Radioisotopes
  • Pyrrolidinones
  • Receptor, Cannabinoid, CB1
  • Tritium