Abstract
Antihistamines are the efficacious drugs to be used for the symptomatic relief of allergic diseases. The safety issue of antihistaminesis of central importanceb ecause of their widespreaduse in current medical practice. Positrone mission tomography (PET) was used to better understand the pharmacological effects of antihistamines on the central nervous system. The H1 receptor occupancy was examined in young male volunteers with [11C]-doxepianf ter the oral or intravenous administration of antihistamines. In other studies, the cognitive performance was also measured tachistoscopically before and after taking antihistamines. The H1 receptor occupancy in the human cortex caused by antihistaminesis significantly correlated with the reported values of incidence of sleepiness in clinical trials, and the occupancy is wellproportional to the impaired cognitive performance. To understand the brain mechanism of antihistamine-induced “sleepiness and impaired cognition”, the regional cerebral blood flow (rCBF) during the task was measured using 3D-PET and H215O before and after administration of d-chlorpheniramine. After its administration, the rCBF was significantly decreased on the bilateral middle temporal gyrus, midbrain and anterior cingulate. These findings suggest that H1 receptor blockade would be affected on the activity of the attention and cognitive system in the brain.
