Ž . European Journal of Pharmacology 331 1997 221–225 Short communication Econazole, miconazole and SK & F 96365 inhibit depolarization-induced and receptor-operated contraction of guinea-pig isolated trachea in vitro Liang Li a , Hannu Kankaanranta b, ) , Kirsi Vaali a , Ilari Paakkari a , Heikki Vapaatalo a a Institute of Biomedicine, Department of Pharmacology and Toxicology, P.O. Box 8, FIN-00014 UniÕersity of Helsinki, Helsinki, Finland b Medical School, UniÕersity of Tampere, P.O. Box 607, FIN-33101 Tampere, Finland Received 2 April 1997; revised 2 June 1997; accepted 6 June 1997 Abstract Econazole, miconazole, SK & F 96365 and nifedipine inhibited Ca 2q - and depolarization-induced and receptor-operated contraction of guinea-pig isolated trachea. Econazole, miconazole and SK & F 96365 inhibited histamine- and methacholine-induced tracheal contraction more than nifedipine. Nifedipine was more potent in inhibiting KCl-induced contraction. Nifedipine, salbutamol and theophylline, but not econazole, miconazole or SK & F 96365, relaxed KCl, histamine-, and methacholine-precontracted trachea. It appears that in the guinea-pig tracheal smooth muscle, econazole, miconazole and SK & F 96365 behave differently from nifedipine, theophylline and salbutamol. Econazole, miconazole and SK & F 96365 are thus introduced as novel antagonists of receptor-operated airway smooth muscle contraction. q 1997 Elsevier Science B.V. Keywords: Ca 2q ; Contraction; Trachea; Econazole; Miconazole; SK & F 96365; Nifedipine 1. Introduction Contractile mechanisms in airway smooth muscle can be divided into receptor-operated and depolarization-in- duced contraction mechanisms. Single channel and whole- cell patch clamp studies have shown the existence of voltage-dependent calcium channels in canine, guinea pig, Ž rat and human airway smooth muscle for review, see . Knox and Tattersfield, 1994 . The classical L-type voltage-dependent calcium channel antagonists inhibit de- polarization-induced contraction of airway smooth muscle. In addition, they have been shown to partially reverse the Ž contractile responses of several receptor agonists e.g., . histamine and cholinergic agonists in vitro. In contrast, in Ž . vivo, dihydropyridine nifedipine , phenylalkylamine Ž . Ž . verapamil and benzothiazepine diltiazem calcium chan- nel antagonists have shown only small and inconsistent effects on the airway response to cold air, histamine, Ž methacholine and antigen Barnes, 1985; Knox and Tat- . tersfield, 1994 . Recently, a novel receptor-operated cal- cium entry pathway has been shown to be responsible for calcium entry during the maintenance phase of the contrac- Ž tile response in cultured human airway cells Murray and ) Ž . Ž . Corresponding author. Tel.: 358-3 215-6687; Fax: 358-3 215-6170; e-mail: blhaka@uta.fi . Kotlikoff, 1991 . Antagonists of receptor-operated calcium entry have been lacking and there are no reports on their effects on airway smooth muscle function. Imidazole an- timycotic drugs econazole and miconazole have recently been reported to antagonize receptor-mediated calcium Ž . influx in neutrophils Montero et al., 1991 and voltage-de- pendent Ca 2q channels in GH3 pituitary and chromaffin Ž . cells Villalobos et al., 1992 . Thus we devised experi- ments aimed to test whether econazole and miconazole could inhibit Ca 2q -induced, receptor-operated and depolar- ization-induced contraction of guinea-pig isolated trachea. The effects of econazole and miconazole were compared with those of SK & F 96365, an experimental antagonist of receptor-mediated calcium entry as described in neu- Ž trophils, lymphocytes, platelets and endothelial cells Mer- . ritt et al., 1990; Nordstrom et al., 1992 ; nifedipine, a ¨ classical antagonist of L-type voltage-dependent calcium channels; salbutamol, a b -agonist; and theophylline, an 2 unspecific phosphodiesterase inhibitor. 2. Materials and methods 2.1. Guinea-pig isolated trachea Ž . English shorthair tricolored guinea pigs 350–530 g of either sex were used in these studies. Following pento- 0014-2999r97r$17.00 q 1997 Elsevier Science B.V. All rights reserved. Ž . PII S0014-2999 97 01068-6