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Spasmolytic effects of three harmala alkaloids on guinea-pig isolated trachea.

The present study examined and compared the spasmolytic effects of 3 harmala alkaloids, harmine, harman, and harmaline, on carbachol-, histamine-, and KCl-induced contractions of guinea-pig isolated tracheal preparations. All 3 compounds relaxed the tracheal preparations contracted by these spasmogens with similar or different EC50 values, harmine being the most potent one. The cumulative concentration-response curves of all 3 compounds for carbachol-induced contraction were shifted to the right by propranolol (1 microM) pretreatment, indicating the involvement of the activation on the beta-adrenoceptors. All 3 compounds shifted the concentration-response curves of carbachol to the right in a parallel manner with the pA2 values comparable with their relaxation EC50 values, indicating a competitive antagonism at the muscarinic receptors. Receptor binding assays indicated that all 3 compounds interacted with lung muscarinic receptors (Ki = 11-13 microM), histamine H1 receptors (Ki = 27-107 microM), and beta2-adrenoceptors (Ki = 20-51 microM). Therefore, in addition to their actions on receptor-linked and voltage-dependent Ca2+ channels as reported in other types of smooth muscle, the present study suggests that the actions on muscarinic receptors, histamine H1 receptors, and beta2-adrenoceptors are also involved in their spasmolytic effects on airway smooth muscles.