N-desmethyl Azelastine is an active metabolite of the histamine H1 receptor antagonist azelastine .1,2 It is formed from azelastine primarily by the cytochrome P450 (CYP) isoforms CYP3A4 and CYP2D6 and, to a lesser extent, by CYP1A2.2 N-desmethyl Azelastine (1 µM) inhibits acetylcholine-induced depolarization and contractions in isolated human tracheal smooth muscle.1 It also inhibits transport of daunorubicin and digoxin in LLC-GA5-CoL150 cells overexpressing P-glycoprotein (P-gp), also known as multidrug resistance protein 1 (MDR1; IC50s = 11.8 and 41.8 µM, respectively).3
1.Richards, I.S., Miller, L., Solomon, D., et al.Azelastine and desmethylazelastine suppress acetylcholine-induced contraction and depolarization in human airway smooth muscleEur. J. Pharmacol.186(2-3)331-334(1990) 2.Nakajima, M., Nakamura, S., Tokudome, S., et al.Azelastine N-demethylation by cytochrome P-450 (CYP)3A4, CYP2D6, and CYP1A2 in human liver microsomes: Evaluation of approach to predict the contribution of multiple CYPsDrug Metab. Dispos.27(12)1381-1391(1999) 3.Katoh, M., Nakajima, M., Yamazaki, H., et al.Inhibitory effects of CYP3A4 substrates and their metabolites on P-glycoprotein-mediated transportEur. J. Pharm. Sci.12(4)505-513(2001)