Azelastine and desmethylazelastine suppress acetylcholine-induced contraction and depolarization in human airway smooth muscle.
We examined the effects of a new anti-asthmatic drug, azelastine, and its principal metabolite, desmethylazelastine, on the in vitro electromechanical response of human airway smooth muscle during cholinergic stimulation. Membrane potential and isometric force were simultaneously measured using an intracellular microelectrode and a microforce transducer. Desmethylazelastine significantly suppressed acetylcholine-induced depolarization and contraction at 10(-6) M, whereas azelastine produced similar results at 10(-4) M, suggesting that the metabolite may be the principal compound acting upon the airway smooth muscle cell.
Richards
I S
IS
Department of Environmental and Occupational Health, College of Public Health, University of South Florida, Tampa 33612.
Miller
L
L
Solomon
D
D
Kulkarni
A
A
Brooks
S
S
Sperelakis
N
N
D000109:Acetylcholine / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004594:Electrophysiology; D006634:Histamine H1 Antagonists / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007537:Isometric Contraction; D008564:Membrane Potentials / Q000187:drug effects; D008839:Microelectrodes; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D010793:Phthalazines / Q000494:pharmacology*; D014132:Trachea / Q000187:drug effects
D006634:Histamine H1 Antagonists; D010793:Phthalazines; C054114:desmethylazelastine; D000109:Acetylcholine; C020976:azelastine