Effects of levocetirizine and diphenhydramine on regional glucose metabolic changes and hemodynamic responses in the human prefrontal cortex during cognitive tasks

• Published in: Human psychopharmacology 2018-03, Vol.33 (2), p.e2655-n/a
• Main Authors: Kikuchi, Asuka, Nasir, Fairuz Binti Mohammadi, Inami, Akie, Mohsen, Attayeb, Watanuki, Shoichi, Miyake, Masayasu, Takeda, Kazuko, Koike, Daigo, Ito, Takayasu, Sasakawa, Junpei, Matsuda, Rin, Hiraoka, Kotaro, Maurer, Marcus, Yanai, Kazuhiko, Watabe, Hiroshi, Tashiro, Manabu
• Format: Article
• Language: English
• Subjects: Adults; Antihistamines; Brain; Brain Mapping; Capillaries; Cetirizine - pharmacology; Cognition - drug effects; Cognitive ability; Cognitive tasks; Cross-Over Studies; Diphenhydramine; Diphenhydramine - pharmacology; Double-Blind Method; Emission measurements; Energy measurement; FDG‐PET; Female; Fluorodeoxyglucose F18 - pharmacokinetics; Glucose; Glucose - metabolism; Healthy Volunteers; Hemodynamic responses; Hemodynamics; Hemodynamics - drug effects; Hemoglobin; Histamine H1 Antagonists - pharmacology; Human behavior; Humans; Image Processing, Computer-Assisted; Infrared spectroscopy; levocetirizine; Male; Metabolism; Neuropsychological Tests; NIRS; Perfusion; Permeability; Positron emission tomography; Prefrontal cortex; Prefrontal Cortex - blood supply; Prefrontal Cortex - diagnostic imaging; Prefrontal Cortex - drug effects; sedation; Sleep and wakefulness; Sleepiness; Spectroscopy, Near-Infrared; Test procedures; Time Factors; Young adults
• ISSN: 0885-6222; 1099-1077
• DOI: 10.1002/hup.2655

Objective Antihistamines often have sedative side effects. This was the first study to measure regional cerebral glucose (energy) consumption and hemodynamic responses in young adults during cognitive tests after antihistamine administration. Methods In this double‐blind, placebo‐controlled, three‐way crossover study, 18 healthy young Japanese men received single doses of levocetirizine 5 mg and diphenhydramine 50 mg at intervals of at least six days. Subjective feeling, task performances, and brain activity were evaluated during three cognitive tests (word fluency, two‐back, and Stroop). Regional cerebral glucose consumption changes were measured using positron emission tomography with [18F]fluorodeoxyglucose. Regional hemodynamic responses were measured using near‐infrared spectroscopy. Results Energy consumption in prefrontal regions was significantly increased after antihistamine administration, especially diphenhydramine, whereas prefrontal hemodynamic responses, evaluated with oxygenated hemoglobin levels, were significantly lower with diphenhydramine treatment. Stroop test accuracy was significantly impaired by diphenhydramine, but not by levocetirizine. There was no significant difference in subjective sleepiness. Conclusions Physiological “coupling” between metabolism and perfusion in the healthy human brain may not be maintained under pharmacological influence due to antihistamines. This uncoupling may be caused by a combination of increased energy demands in the prefrontal regions and suppression of vascular permeability in brain capillaries after antihistamine treatment. Further research is needed to validate this hypothesis.