Quantification of Neuroreceptors in the living human brain. II. Inhibition studies of receptor density and affinity

J Cereb Blood Flow Metab. 1986 Apr;6(2):147-53. doi: 10.1038/jcbfm.1986.28.

Abstract

A method for estimating receptor density (Bmax) in the living human brain by positron emission tomography was exemplified by a ligand, 3-N-[11C]methylspiperone ([11C]NMSP), that binds to D2 dopamine receptors with high affinity. The ligand binds essentially irreversibly (i.e., with very little dissociation) to the receptors during the 2-h scanning period. Transfer constants were estimated at steady state. In a previous article, we presented a method for the determination of k3, the rate of binding of the labeled ligand. In the present work, we varied k3 by reducing the number of available receptors with a previously administered receptor blocking agent, haloperidol. We calculated a receptor density of 9.2 pmol g-1 in the caudate nucleus of four normal volunteers, and an inhibitory constant of haloperidol of 1.4 nM by comparing tracer accumulation in the absence and the presence of the blocking agent. The values agreed with measurements of NMSP receptor density and haloperidol inhibitory potency in vitro in brain homogenates from human autopsy material.

MeSH terms

  • Adolescent
  • Adult
  • Brain / diagnostic imaging
  • Brain / metabolism*
  • Caudate Nucleus / metabolism
  • Haloperidol / pharmacology
  • Humans
  • Kinetics
  • Ligands
  • Male
  • Middle Aged
  • Models, Biological
  • Radioligand Assay
  • Receptors, Dopamine / drug effects
  • Receptors, Dopamine / metabolism*
  • Receptors, Dopamine D2
  • Sensory Receptor Cells / drug effects
  • Sensory Receptor Cells / metabolism*
  • Spiperone / analogs & derivatives
  • Tomography, Emission-Computed

Substances

  • Ligands
  • Receptors, Dopamine
  • Receptors, Dopamine D2
  • Spiperone
  • 3-N-methylspiperone
  • Haloperidol