Premium
Histamine H 1 receptor occupancy in human brains after single oral doses of histamine H 1 antagonists measured by positron emission tomography
Author(s) -
Yanai Kazuhiko,
Ryu Jong Hoon,
Watanabe Takehiko,
Iwata Ren,
Ido Tatsuo,
Sawai Yoneichi,
Ito Kazumi,
Itoh Masatoshi
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb16386.x
Subject(s) - histamine h1 receptor , antihistamine , doxepin , terfenadine , histamine , receptor , pharmacology , chemistry , human brain , histamine receptor , histamine h1 antagonists , positron emission tomography , medicine , endocrinology , antagonist , nuclear medicine , psychiatry
1 Histamine H 1 receptor occupancy in the human brain was measured in 20 healthy young men by positron emission tomography (PET) using [ 11 C]‐doxepin. 2 (+)‐Chlorpheniramine, a selective and classical antihistamine, occupied 76.8±4.2% of the averaged values of available histamine H 1 receptors in the frontal cortex after its administration in a single oral dose of 2 mg. Intravenous administration of 5 mg (+)‐chlorpheniramine almost completely abolished the binding of [ u C]‐doxepin to H 1 receptors (H 1 receptor occupancy: 98.2±1.2%). 3 Terfenadine, a nonsedative antihistamine, occupied 17.2±14.2% of the available H 1 receptors in the human frontal cortex after its administration in a single oral dose of 60 mg. 4 There was no correlation between H 1 receptor occupancy by terfenadine and the plasma concentration of the active acid metabolite of terfenadine in each subject. 5 PET data on human brain were essentially compatible with those on H 1 receptor occupancy in guinea‐pig brain determined by in vivo binding techniques, although for the same H 1 receptor occupancy the dose was less in human subjects than in guinea‐pigs. 6 The PET studies demonstrated the usefulness of measuring H 1 receptor occupancy with classical and second‐generation antihistamines in human brain to estimate their unwanted side effects such as sedation and drowsiness quantitatively.