Biological Activity
Fenspiride-d5 is intended for use as an internal standard for the quantification of fenspiride by GC- or LC-MS. Fenspiride is an antagonist of histamine H1 receptors and a non-steroidal anti-inflammatory drug (NSAID).1,2 It inhibits histamine-induced contraction of isolated guinea pig trachea but not histamine-induced inotropy of isolated guinea pig heart. It also inhibits phosphodiesterase 4 (PDE4), PDE5, and PDE3 (IC50s = 69, ~158, and 363 μM, respectively, in isolated human bronchi derived from patients with lung cancer).3 It is selective for these phosphodiesterases over PDE1 and PDE2, where it provides less than 25% inhibition. Fenspiride potentiates the airway relaxant effects of isoproterenol and sodium nitroprusside indicating an effect on cAMP and cGMP phosphodiesterases, respectively. Aerosolized fenspiride (1 mg/ml) reverses bronchoconstriction induced by capsaicin and, when used at aerosolized concentrations ranging from 1-10 mg/ml, reduces cough induced by citric acid in a guinea pig model of cough.2
References
1.Rognoni, F., Marchini, F., Piacenza, G., et al.Effect of 8-N-phenethyl-1-oxa-2-oxo-3,8-diazaspiro(4,5)decane hydrochloride (decaspiride) on histamine receptorsBoll. Chim. Farm.117(7)397-401(1978)
2.Laude, E.A., Bee, D., Crambes, O., et al.Antitussive and antibronchoconstriction actions of fenspiride in guinea-pigsEur. Respir. J.8(10)1699-1704(1995)
3.Cortijo, J., Naline, E., Ortiz, J.L., et al.Effects of fenspiride on human bronchial cyclic nucleotide phosphodiesterase isoenzymes: Functional and biochemical studyEur. J. Pharmacol.341(1)79-86(1998)
