title: Next-day residual sedative effect after nighttime administration of an over-the-counter antihistamine sleep aid, diphenhydramine, measured by positron emission tomography.
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, frontotemporal 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.
authors.affiliation: Department of Pharmacology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
authors.forename: Dongying
authors.initials: D
authors.lastname: Zhang
authors.forename: Manabu
authors.initials: M
authors.lastname: Tashiro
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Shibuya
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Okamura
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Funaki
authors.forename: Takeo
authors.initials: T
authors.lastname: Yoshikawa
authors.forename: Masato
authors.initials: M
authors.lastname: Kato
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Yanai
mesh_terms: D000284:Administration, Oral; D001921:Brain / Q000378:metabolism; D018592:Cross-Over Studies; D004155:Diphenhydramine / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D004311:Double-Blind Method; D006634:Histamine H1 Antagonists / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D006801:Humans; D006993:Hypnotics and Sedatives / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics; D008297:Male; D004366:Nonprescription Drugs; D010880:Piperidines / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D049268:Positron-Emission Tomography / Q000379:methods*; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects* / Q000493:pharmacokinetics; D011969:Receptors, Histamine H1 / Q000378:metabolism; D007319:Sleep Initiation and Maintenance Disorders / Q000188:drug therapy; D055815:Young Adult
chemical_list: D006634:Histamine H1 Antagonists; D006993:Hypnotics and Sedatives; D004366:Nonprescription Drugs; D010880:Piperidines; D011725:Pyridines; D011969:Receptors, Histamine H1; C511534:bepotastine besilate; D004155:Diphenhydramine