Brain histamine H₁ receptor occupancy measured by PET after oral administration of levocetirizine, a non-sedating antihistamine

Objective: Histamine H₁ receptor (H₁R) antagonists often have sedative side effects, which are caused by the blockade of the neural transmission of the histaminergic neurons. We examined the brain H₁R occupancy (H₁RO) and the subjective sleepiness of levocetirizine, a new second-generation antihistamine, comparing fexofenadine, another non-sedating antihistamine, as a negative active control. Methods: Eight healthy volunteers underwent positron emission tomography (PET) imaging with [¹¹C]doxepin, a PET tracer that specifically binds to H₁Rs, after a single oral administration of levocetirizine (5 mg), fexofenadine (60 mg) or placebo in a double-blind crossover study. Binding potential ratios and H₁ROs in the cerebral cortices regions were calculated using placebo. Subjective sleepiness was assessed with the Line Analogue Rating Scale and the Stanford Sleepiness Scale. Results: There was no significant difference between the mean brain H₁RO after levocetirizine administration (8.1%; 95% CI: -9.8 to 26.0%) and fexofenadine administration (-8.0%; 95% CI: -26.7 to 10.6%). Similarly, subjective sleepiness was not significantly different between the two antihistamines and placebo. Neither subjective sleepiness nor plasma concentrations was significantly correlated with the brain H₁RO of the two antihistamines. Conclusion: At therapeutic dose, levocetirizine does not bind significantly to the brain H₁Rs and does not induce significant sedation.