Epinastine (WAL 801CL) inhibits the electrical field stimulation-induced cholinergic contraction in guinea pig and human airways in vitro

Epinastine is an antihistamine drug with binding affinities at 5-hydroxytry ptamine (5-HT) receptors, The current study was performed to investigate wh ether epinastine could modulate the cholinergic contraction in guinea pig a nd human airways in vitro. Isolated guinea pig and human airway preparations were suspended in organ b aths containing modified Krebs-Henseleit solution. Electrical field stimula tion was applied to elicit cholinergic contractions. Epinastine produced a concentration-dependent inhibition of the cholinergic contraction in guinea pig airways and pretreatment with methysergide (5-HT 1/2/7 antagonist) significantly attenuated these inhibitory effects of epin astine. Pretreatment with tropisetron (5-HT3/4 antagonist), ketanserin (5-H T2 antagonist), SDZ216-525 (5-HT1A antagonist) or phentolamine (alpha-adren ergic antagonist) had no effect. Epinastine did not displace the concentrat ion-response curve to acetylcholine. These results suggest that epinastine inhibits the cholinergic contraction in guinea pig airways through stimulation of prejunctional 5-hydroxytryptam ine receptors, Located to postganglionic cholinergic nerves. Inhibitory eff ects of epinastine on the cholinergic contraction in human airways in vitro were also demonstrated, which suggests that a similar mechanism might be p resent in human airways, The pharmacological profile of epinastine, which s hows binding affinity at the 5-hydroxytryptamine(7) receptor but not at the 5-hydroxytryptamine(1) receptor subtypes corroborates the hypothesis that the inhibitory prejunctional 5-hydroxytryptamine receptor on cholinergic ne rves is of the 5-hydroxytryptamine(7) subtype.