Original ContributionsNext-Day Residual Sedative Effect After Nighttime Administration of an Over-the-Counter Antihistamine Sleep Aid, Diphenhydramine, Measured by Positron Emission TomographyZhang, Dongying MD*†; Tashiro, Manabu MD, PhD‡; Shibuya, Katsuhiko MS*; Okamura, Nobuyuki MD, PhD*; Funaki, Yoshihito PhD§; Yoshikawa, Takeo MD, PhD*; Kato, Masato MD, PhD∥; Yanai, Kazuhiko MD, PhD*‡Author Information From the *Department of Pharmacology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan; †Department of Anaesthesiology, First Affiliated Hospital, China Medical University, Shenyang, China; ‡Division of Cyclotron Nuclear Medicine, and §Division of Radiopharmaceutical Chemistry, Cyclotron and Radioisotope Centre, Tohoku University; and ∥Department of Anaesthesiology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan. Received February 4, 2010; accepted after revision August 4, 2010. Reprints: Kazuhiko Yanai, MD, PhD, Department of Pharmacology, Graduate School of Medicine, Tohoku University, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan (e-mail: [email protected]). This work was supported in part by Grants-in-Aid for Scientific Research (No. 21650088 for Dr Yanai) from the Japan Society for Promotion of Science as well as by a grant from the Japan Society for Technology on research and education in "molecular imaging." Journal of Clinical Psychopharmacology: December 2010 - Volume 30 - Issue 6 - p 694-701 doi: 10.1097/JCP.0b013e3181fa8526 Buy Metrics Abstract Antihistamines often are self-administered at night as over-the-counter (OTC) sleep aids, but their next-day residual sedative effect has never been evaluated using a reliable quantitative method such as positron emission tomography (PET). We performed a double-blind, placebo-controlled, crossover study in which we evaluated the residual effect the next day after nighttime administration of diphenhydramine, a commonly used OTC sleep aid, in terms of brain H1 receptor occupancy (H1RO) measured using 11C-doxepin-PET. We also compared the results of diphenhydramine with those of bepotastine, a second-generation antihistamine. Eight healthy adult male subjects underwent PET measurement the morning (11:00) after random oral administration of diphenhydramine (50 mg), bepotastine (10 mg), or placebo the night before (23:00). Binding potential ratios and H1ROs were calculated in different brain regions of interest such as the cingulate gyrus, fronto-temporal cortex, and cerebellum. Subjective sleepiness and plasma drug concentration also were measured. Calculation of binding potential ratios revealed significantly lower values for diphenhydramine than for bepotastine or placebo in all regions of interest (P < 0.01). Cortical mean H1RO after diphenhydramine treatment was 44.7% compared with 16.6% for bepotastine treatment (P < 0.01). Subjective sleepiness was not significantly different among the subjects treated with each test drug or the placebo. In conclusion, the next-day residual sedative effect after nighttime administration of the OTC sleep aid diphenhydramine was verified for the first time by direct PET measurement of H1RO. Taking into account the possible hangover effect of OTC antihistamine sleep aids, care needs to be taken during their administration. © 2010 by Lippincott Williams & Wilkins.