Fenspiride is an antagonist of H1-histamine receptors. Fenspiride is an orally active non-steroidal anti-inflammatory agent that can be used for the treatment of respiratory tract infections and otitis media. Fenspiride inhibited phosphodiesterase 4 and phosphodiesterase 3 activities with -logIC50 values of 4.16+/-0.09 and 3.44+/-0.12, respectively. Phosphodiesterase 5 activity was also inhibited with a -logIC50 value of approximately 3.8.

Fenspiride (approximately 100 μM) inhibits histamine-induced tracheal constriction in the isolated guinea pig. Fenspiride (< or = 10(-3) M) produced less than 25% inhibition of phosphodiesterase 1 and phosphodiesterase 2 activities [2].

Administered orally at 60 mg/kg for 3 days, Fenspiride reduced the lipopolysaccharide-induced early rise of tumor necrosis factor concentrations in serum (4.2 + 0.9 vs. 2.3 + 0.5 ng/ml, P < 0.05) and in the bronchoalveolar lavage fluid (55.7 + 20 vs. 19.7 + 7.5 ng/ml, P < 0.05) of the model of endotoxemia that also reduced the lipopolysaccharide-induced primed stimulation of alveolar macrophages [3]. Administered orally at 60 mg/kg for 3 days, Fenspiride reduced the increased serum concentrations of extracellular type II phospholipase A 2, the intensity of the neutrophilic alveolar invasion, and the lethality due to the lipopolysaccharide [3].