EFFECTS OF EPINASTINE HYDROCHLORIDE ON CHOLINERGIC NEUROEFFECTOR TRANSMISSION IN CANINE TRACHEAL SMOOTH-MUSCLE

We determined the effects of epinastine hydrochloride, an anti-asthmat ic drug, on cholinergic neuro-effector transmission in canine trachea. Isometric tension of tracheal strips was measured in the presence of indomethacin and propranolol. Epinastine (10(-6) M) significantly supp ressed the contraction evoked by electrical field stimulation, but had no effect on the acetylcholine-evoked contraction. An L-type Ca2+ cha nnel blocker, nicardipine, did not suppress the electrical field stimu lation-induced smooth muscle contraction and did not alter the inhibit ory effect of epinastine. An N-type Ca2+ channel blocker, omega-conoto xin, suppressed the electrical field-stimulation-induced contraction i n a dose-dependent manner, and in a subthreshold/intermediate concentr ation abolished the inhibitory effect of epinastine. These findings in dicate that epinastine exerts prejunctional inhibitory effects on airw ay smooth muscle of dogs, presumably by inhibiting acetylcholine relea se from vagal nerve terminals, and suggest that this effect is mediate d by N-type Ca2+ channels. (C) 1998 Elsevier Science B.V. All rights r eserved.