Histamine is detected in high concentrations in the airways during an allergic
asthma response. In a murine model of allergic
asthma, the
histamine H4 receptor (H4R)-selective
ligand JNJ 7777120 reduces
asthma-like symptoms. A sole antagonistic function of
JNJ 7777120 at the murine H4R has, however, been questioned in the literature. Therefore, in the present study, we aimed at analyzing the effects of
JNJ 7777120 in comparison to that of the H3/4R-selective antagonist
thioperamide. Experimental murine
asthma was induced by sensitization and provocation of BALB/c mice with ovalbumine (OVA).
JNJ 7777120,
thioperamide, or JNJ 5207852, an H3R-selective antagonist which was used to dissect H3R- and H4R-mediated activities of
thioperamide, were injected subcutaneously during sensitization and effects were analyzed after provocation. Pharmacokinetic analyses revealed shortest t1/2 values in both plasma and lung tissue and lowest maximal concentration in lung tissue for
JNJ 7777120 in comparison to
thioperamide and JNJ 5207852. Nevertheless,
JNJ 7777120 reduced serum titers of
allergen-specific (anti-OVA)
IgE, inflammatory infiltrations in lung tissue, and
eosinophilia in bronchoalveolar lavage fluid. In contrast,
thioperamide reduced only
eosinophilia in bronchoalveolar lavage fluid, while anti-OVA
IgE concentrations and lung infiltrations remained unaffected. JNJ 5207852 had no effect on these parameters.
JNJ 7777120 provides beneficial effects in experimental murine
asthma, which, however, could only partially be mimicked by
thioperamide, despite more favorable pharmacokinetics. Thus, whether these effects of
JNJ 7777120 are entirely attributable to an antagonistic activity at the murine H4R or whether an agonistic activity is also involved has to be reconsidered.