Pharmacological Effects of Ephedrine Alkaloids on Human α₁- and α₂-Adrenergic Receptor Subtypes

Abstract

Ephedra species of plants have both beneficial and adverse effects primarily associated with the presence of ephedrine alkaloids. Few reports have appeared that examine the direct actions of ephedrine alkaloids on human subtypes of adrenergic receptors (ARs). In the present study, ephedrine alkaloids were evaluated for their binding affinities on human ␣ 1A -, ␣ 1B -, ␣ 1D -, ␣ 2A -, ␣ 2B -, and ␣ 2C -AR subtypes expressed in HEK and Chinese hamster ovary cells. Cell-based reporter gene assays were used to establish functional activity of ephedrine alkaloids at ␣ 1A -, ␣ 2A -, and ␣ 2C -ARs. The data showed that ephedrine alkaloids did not activate ␣ 1 -and ␣ 2 -ARs and that they antagonized the agonist-mediated effects of phenylephrine and medetomidine on ␣ 1 -and ␣ 2 -ARs, respectively. As in the binding studies, 1R,2R-and 1R,2S-ephedrine showed greater functional antagonist activity than the 1S,2R-and 1S,2S-isomers. The rank order of affinity for the isomers was 1R,2R Ͼ 1R,2S Ͼ 1S,2R Ͼ 1S,2S. The rank order of potencies of alkaloids containing a 1R,2S-configuration was norephedrine Ն ephedrine Ͼ Ͼ N-methylephedrine. These studies have demonstrated that orientation of the ␤-hydroxyl group on the ethylamino side chain and the state of N-methyl substitution are important for ␣-AR binding and functional activity of the ephedrine alkaloids. In conclusion, the ephedrine isomers and analogs studied did not exhibit any direct agonist activity and were found to possess moderate antagonist activities on cloned human ␣-ARs.

Allelopathic Potential of Select Gymnospermous Trees

“…Nasr and Shariati (2005) reported that different concentrations of ephedrine reduced the seed germination of Astragalus cycluphyllus. Ephedrine exhibits optical isomerism and has two chiral centers, giving rise to four stereoisomers; by convention, enantiomers with opposite stereochemistry around the chiral centers are designated as ephedrine, while pseudoephedrine has same stereochemistry around the chiral carbons (Ma et al 2007). A reduction in seed germination of perennial ryegrass was consistent with different concentrations of the stock Ephedra extract (Fig.…”

Ephedrine Alkaloids-Free Ephedra Herb Extract, EFE, Has No Adverse Effects Such as Excitation, Insomnia, and Arrhythmias

“…24,25) In contrast, ephedrine alkaloids are known to express their pharmacological actions via the α-and β-adrenergic receptors, and are reported to induce release of endogenous catecholamines, such as noradrenaline and dopamine, indirectly and to prevent their neuronal reuptake. 26) Noradrenaline is one of the most abundant neurotransmitters in the central and peripheral nervous systems, and is implicated in many aspects of physiology and behavior, including cognition, attention, reward, locomotion, and arousal. Smallmolecule activators of noradrenaline signaling have been shown to increase wakefulness, whereas inhibitors promote sleep.…”

Ephedrine: direct, indirect or mixed acting sympathomimetic?

“…Cell-based receptor gene assays were used to establish functional activity of ephedrine alkaloids at α1A, α2A, and α2C adrenergic receptors. 40 Previously, Vansal and Feller (1999) also evaluated direct effects of the ephedrine isomers on human β1, β2, and β3 adrenergic receptors expressed in Chinese hamster ovary cells.…”