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

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Nakai T, Kitamura N, Hashimoto T, Kajimoto Y, Nishino N, Mita T, Tanaka C

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

Biol Psychiatry. 1991 Aug 15;30(4):349-56.

PubMed ID

1912125 [ View in PubMed

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Abstract

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.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Diphenylpyraline	Histamine H1 receptor	Protein	Humans	Yes	Antagonist	Details