Brain histamine H₁ receptor occupancy after oral administration of desloratadine and loratadine

Some histamine H₁ receptor (H₁R) antagonists induce adverse sedative reactions caused by blockade of histamine transmission in the brain. Desloratadine is a second-generation antihistamine for treatment of allergic disorders. Its binding to brain H₁Rs, which is the basis of sedative property of antihistamines, has not been examined previously in the human brain by positron emission tomography (PET). We examined brain H₁R binding potential ratio (BPR), H₁R occupancy (H₁RO), and subjective sleepiness after oral desloratadine administration in comparison to loratadine. Eight healthy male volunteers underwent PET imaging with [¹¹C]-doxepin, a PET tracer for H₁Rs, after a single oral administration of desloratadine (5 mg), loratadine (10 mg), or placebo in a double-blind crossover study. BPR and H₁RO in the cerebral cortex were calculated, and plasma concentrations of loratadine and desloratadine were measured. Subjective sleepiness was quantified by the Line Analogue Rating Scale (LARS) and the Stanford Sleepiness Scale (SSS). BPR was significantly lower after loratadine administration than after placebo (0.504 ± 0.074 vs 0.584 ± 0.059 [mean ± SD], P < 0.05), but BPR after desloratadine administration was not significantly different from BPR after placebo (0.546 ± 0.084 vs 0.584 ± 0.059, P = 0.250). The plasma concentration of loratadine was negatively correlated with BPR in subjects receiving loratadine, but that of desloratadine was not correlated with BPR. Brain H₁ROs after desloratadine and loratadine administration were 6.47 ± 10.5% and 13.8 ± 7.00%, respectively (P = 0.103). Subjective sleepiness did not significantly differ among subjects receiving the two antihistamines and placebo. At therapeutic doses, desloratadine did not bind significantly to brain H₁Rs and did not induce any significant sedation.