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

The present study examined and compared the spasmolytic effects of 3 harmal a alkaloids, harmine, harman, and harmaline, on carbachol-, histamine-, and KCI-induced contractions of guinea-pig isolated tracheal preparations. All 3 compounds relaxed the tracheal preparations contracted by these spasmoge ns with similar or different EC50 values, harmine being the most potent one . The cumulative concentration-response curves of all 3 compounds for carba chol-induced contraction were shifted to the right by propranolol (I VM) pr etreatment, indicating the involvement of the activation on the beta -adren oceptors. All 3 compounds shifted the concentration-response curves of carb achol to the right in a parallel manner with the pA(2) values comparable wi th their relaxation EC50 values, indicating a competitive antagonism at the muscarinic receptors. Receptor binding assays indicated that all 3 compoun ds interacted with lung muscarinic receptors (K-i = 11-13 muM), histamine H -1 receptors (K-i = 27-107 muM), and beta (2)-adrenoceptors (K-i = 20-51 mu M). Therefore, in addition to their actions on receptor-linked and voltage- dependent Ca2+ channels as reported in other types of smooth muscle, the pr esent study suggests that the actions on muscarinic receptors, histamine H- 1 receptors, and beta (2)-adrenoceptors are also involved in their spasmoly tic effects on airway smooth muscles.