Decreased histamine H1 receptors in the frontal cortex of brains from patients with chronic schizophrenia

Biol Psychiatry. 1991 Aug 15;30(4):349-56. doi: 10.1016/0006-3223(91)90290-3.


Involvement of histamine H1 receptor in the brains of schizophrenic patients was investigated using 3H-mepyramine as a ligand. The specific 3H-mepyramine binding in the frontal cortex was saturable with the dissociation constant (Kd) of about 0.6 nM and the maximum number of binding sites (Bmax) of 64 fmol/mg protein. Specific H1 antagonists, mepyramine (Ki = 1.4 nM), promethazine (Ki = 1.4 nM), diphenylpyraline (Ki = 4.1 nM), triprolidine (Ki = 5.3 nM), diphenylhydramine (Ki = 35 nM), but not the specific H2 antagonist, cimetidine (Ki greater than 10(5) nM), strongly inhibited the 3H-mepyramine binding. Regional distribution of the specific 3H-mepyramine binding was in the order of: frontal cortex greater than hippocampus greater than cerebellum greater than hypothalamus greater than thalamus, putamen, and pallidum. The specific 3H-mepyramine binding in schizophrenic brains was reduced by 56% in the frontal cortex. Representative Scatchard analyses of the specific 3H-mepyramine binding revealed changes resulting from a decrease in receptor density but not in receptor affinity. Down-regulation of the histamine H1 receptor in the frontal cortex may be involved in the pathophysiology of schizophrenia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Brain / metabolism
  • Chronic Disease
  • Female
  • Frontal Lobe / metabolism*
  • Humans
  • Kinetics
  • Male
  • Middle Aged
  • Pyrilamine / metabolism
  • Radioligand Assay
  • Receptors, Histamine H1 / metabolism*
  • Schizophrenia / metabolism*


  • Receptors, Histamine H1
  • Pyrilamine