POSITRON EMISSION TOMOGRAPHIC STUDY OF CENTRAL HISTAMINE H-1-RECEPTOROCCUPANCY IN HUMAN-SUBJECTS TREATED WITH EPINASTINE, A 2ND-GENERATIONANTIHISTAMINE

Histamine H-1-receptor occupancy in the human brain was measured in he althy young volunteers by positron emission tomography (PET) using [C- 11]doxepin. d-Chlorpheniramine, a selective and classical antihistamin e, occupied 76.8 +/- 4.2% of the averaged values of available histamin e H-1 receptors in the frontal cortex after its administration in a si ngle oral dose of 2 mg. Epinastine, a non-sedative antihistamine, occu pied 13.2 +/- 18.5% of the available H-1 receptors in the human fronta l cortex after its administration in a single oral dose of 20 mg. Ther e was significant correlation between H-1-receptor occupancy by epinas tine and its plasma concentration in each subject PET data on the huma n brain were essentially compatible with those on H-1-receptor occupan cy in the guinea pig brain as determined by an in vivo binding techniq ue, although for the same H-1-receptor occupancy rite dose was less in humans than in guinea pigs. Our PET studies demonstrated that recepto r occupancy by a second-generation H-1 antagonist, epinastine, was les s than 20% of the total H-1 receptors, and that the low receptor occup ancy was closely related to the low incidence of central side effects.