Positron emission tomographic study of central histamine H1-receptor occupancy in human subjects treated with epinastine, a second-generation antihistamine
Yanai, K.; Ryu, J.H.; Watanabe, T.; Iwata, R.; Ido, T.; Asakura, M.; Matsumura, R.; Itoh, M.
Methods and Findings in Experimental and Clinical Pharmacology 17(Suppl): 64-69
1995
ISSN/ISBN: 0379-0355 PMID: 8750798 Document Number: 451017
Histamine H-1-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 H-1 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 H-1 receptors in the human frontal cortex after its administration in a single oral dose of 20 mg. There was significant correlation between H-1-receptor occupancy by epinastine and its plasma concentration in each subject. PET data on the human brain were essentially compatible with those on H-1-receptor occupancy in the guinea pig brain as determined by an in vivo binding technique, although for the same H-1-receptor occupancy, the dose was less in humans than in guinea pigs. Our PET studies demonstrated that receptor occupancy by a second-generation H-1 antagonist, epinastine, was less than 20% of the total H-1 receptors, and that the low receptor occupancy was closely related to the low incidence of central side effects.