Positron emission tomographic study of central histamine H1-receptor occupancy in human subjects treated with epinastine, a second-generation antihistamine

K. Yanai, J. H. Ryu, T. Watanabe, Ren Iwata, T. Ido, M. Asakura, R. Matsumura, M. Itoh

Research output: Contribution to journalArticlepeer-review

42 Citations (Scopus)

Abstract

Histamine H1-receptor occupancy in the human brain was measured in healthy young volunteers by positron emission tomography (PET) using [11C]doxepin. d-Chlorpheniramine, a selective and classical antihistamine, occupied 76.8 ± 4.2% of the averaged values of available histamine H1 receptors in the frontal cortex after its administration in a single oral dose of 2 mg. Epinastine, a non-sedative antihistamine, occupied 13.2 ± 18.5% of the available H1 receptors in the human frontal cortex after its administration in a single oral dose of 20 mg. There was significant correlation between H1-receptor occupancy by epinastine and its plasma concentration in each subject. PET data on the human brain were essentially compatible with those on H1-receptor occupancy in the guinea pig brain as determined by an in vivo binding technique, although for the same H1-receptor occupancy, the dose was less in humans than in guinea pigs. Our PET studies demonstrated that receptor occupancy by a second-generation H1 antagonist, epinastine, was less than 20% of the total H1 receptors, and that the low receptor occupancy was closely related to the low incidence of central side effects.

Original languageEnglish
Pages (from-to)64-69
Number of pages6
JournalMethods and Findings in Experimental and Clinical Pharmacology
Volume17
Issue numberSUPPL. C
Publication statusPublished - 1995 Dec 1

Keywords

  • H-receptor antagonists
  • antihistamines
  • brain
  • chlorpheniramine
  • epinastine
  • positron emission tomography
  • receptor occupancy
  • sedation in man

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)

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