PF-03654764 binds with high affinity to the human H3 receptor and with lower affinity to the rat H3 receptor, in addition to having >1000-fold selectivity versus other human histamine receptor subtypes (H1, H2, and H4). PF-03654764 displayed potent antagonist properties in functional assays measuring cAMP utilizing a reporter gene assay (β-lactamase) in HEK293 cells stably expressing full length human or rat H3 receptors. In human hepatic microsomes, PF-03654764 was metabolically stable and were predicted to have low clearance. It has low potential to inhibit activities of CYP 1A2, 2B6, 2C8, 2C9, 2C19, 2D6, and 3A4. PF-03654764 + fexofenadine failed to provide superior relief of allergic rhinitis-associated nasal symptoms upon exposure to ragweed pollen compared to fexofenadine + pseudoephedrine. Side effects in the PF-03654764-treated groups were clinically significant compared to the controls. PF-03654764 had been in phase II clinical trial for the treatment of allergic rhinitis and in phase I clinical trial for the treatment of Alzheimer's disease. However, these investigations were discontinued.