Effects of azelastine on vagal neuroeffector transmission in canine and human airway smooth muscle.
Azelastine is a newly developed antiallergic drug that is reported to antagonize histamine and leukotrienes in addition to its inhibitory action on release of chemical mediators. In the present study, the effects of azelastine on neuroeffector transmission in the airway smooth muscles with double sucrose gap and isometric tension-recording methods were evaluated. Azelastine (10(-8) to 10(-6) mol/L) markedly decreased the contractile response of human bronchial and dog tracheal muscle strips to electrical field stimulation (10 pulses at 20 V, 20 Hz, 800 microseconds) in a dose-dependent manner. In parallel with actions on twitch contractions, azelastine suppressed the amplitude of excitatory junction potentials of dog trachea without changing the resting membrane potential and input resistance of smooth muscle cells. However, azelastine did not alter acetylcholine sensitivity of the smooth muscle cells. These results indicate that azelastine possesses an inhibitory action on the release of acetylcholine by vagal nerve terminals. This inhibitory effect of azelastine may contribute to the treatment of asthma in addition to its antiallergic actions.
Aizawa
H
H
Research Institute for Diseases of the Chest, Kyushu University, Fukuoka, Japan.
Inoue
H
H
Miyazaki
N
N
Ikeda
T
T
Shigematsu
N
N
Ito
Y
Y
D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D001980:Bronchi / Q000187:drug effects* / Q000294:innervation; D004285:Dogs; D005260:Female; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010793:Phthalazines / Q000494:pharmacology*; D011724:Pyridazines / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects; D014132:Trachea / Q000187:drug effects* / Q000294:innervation; D014630:Vagus Nerve / Q000187:drug effects* / Q000378:metabolism
D006634:Histamine H1 Antagonists; D010793:Phthalazines; D011724:Pyridazines; D000109:Acetylcholine; C020976:azelastine