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

Asuka Kikuchi, Fairuz Binti Mohammadi Nasir, Akie Inami, Attayeb Mohsen, Shoichi Watanuki, Masayasu Miyake, Kazuko Takeda, Daigo Koike, Takayasu Ito, Junpei Sasakawa, Rin Matsuda, Kotaro Hiraoka, Marcus Maurer, Kazuhiko Yanai, Hiroshi Watabe, Manabu Tashiro

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

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 [ 18 F]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.

Original languageEnglish
Article numbere2655
JournalHuman Psychopharmacology
Volume33
Issue number2
DOIs
Publication statusPublished - 2018 Mar

Keywords

  • FDG-PET
  • NIRS
  • antihistamines
  • diphenhydramine
  • levocetirizine
  • sedation

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Psychiatry and Mental health
  • Pharmacology (medical)

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