Spasmolytic Effects of Three Harmala Alkaloids onGuinea-Pig Isolated Trachea

Abstract

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.

Modulation of voltage‐gated channel currents by harmaline and harmane

“…This is partially supported by the findings of Shi et al . (2000; 2001), who used binding receptor assays to demonstrate an interaction of the related compound harmine with the 1,4‐dihydropyridine‐binding site of L‐type calcium channels of cardiac cells.…”

“…It appears surprising that, despite these manifold effects of harmale alkaloids on various targets, little information is available about their action on neuronal sodium, potassium and calcium channel currents and calcium homeostasis (Shi et al ., 2001). Especially calcium – entering through membrane channels – acts as a major second messenger, whose intracellular concentration is tightly regulated.…”

Separation and purification of harmine and harmaline from Peganum harmala using pH‐zone‐refining counter‐current chromatography

“…1). These harmala alkaloids have a wide spectrum of pharmacological action including platelet aggregation inhibition [2], monoamine oxidase inhibition [3,4], anxiolytic and behavioral effects [3], spasmolytic effects [5], and immunomodulatory effects [6]. Thus, it is important to develop an efficient method to separate and purify alkaloids from the plants.…”

β-Carboline Alkaloid Constituents from aThermoactinomyces SP.Strain Isolated from Livingston Island, Antarctica

“…These alkaloids are considered to possess pharmacological properties related to the central nervous system -tremorogenesis (12), hypothermia (1), hallucinogenesis (8) and monoamine oxidase inhibition (13,15). In experimental animals (guinea-pigs), harmane, harmine and harmaline have also been demonstrated to cause spasmolytic effects on isolated trachea (17). It has also been reported that harmane alkaloids show antioxidant and radical scavenging properties (9,20), cause inhibition of platelet aggregation (16), exert cytotoxic effects on cancer cell lines (16), and possess anthelmintic and antiprotozoal activities (2).…”