Affinity of neuroleptics for D1 receptor of human brain striatum

J Psychiatry Neurosci. 1994 Jul;19(4):265-9.

Abstract

We determined the inhibition-dissociation constant (Ki) of a number of neuroleptics for D1 receptors of normal human brain tissue using [3H]SCH23390 [R-(+)-8-chloro-2,3,4,5-tetrahydro-3-methyl-5-phenyl-1H-3[benzazepine-7- ol]. SCH23390 had the highest affinity with a Ki of 0.76 nM. Among clinically used drugs, propericiazine showed the highest affinity with a Ki of 10 nM. When neuroleptics were classified according to chemical structures, the Ki values were as follows. Phenothiazines ranged from 10 nM to 250 nM. Butyrophenones ranged from 45 nM to 250 nM. Thioxanthenes ranged from 12 nM to 340 nM. Orthopramines were more than 10,000 nM. The Ki values for the binding site of this study were significantly correlated with those reported in studies using animal brain. The possible relationship between D1 receptors and negative symptoms is discussed.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Antipsychotic Agents / classification
  • Antipsychotic Agents / pharmacology*
  • Binding Sites / drug effects*
  • Butyrophenones / pharmacology*
  • Corpus Striatum / metabolism*
  • Culture Techniques
  • Female
  • Humans
  • Male
  • Middle Aged
  • Phenothiazines / pharmacology*
  • Radioligand Assay
  • Receptors, Dopamine D1 / metabolism*

Substances

  • Antipsychotic Agents
  • Butyrophenones
  • Phenothiazines
  • Receptors, Dopamine D1
  • periciazine