Submitted to: Planta Medica
Publication Type: Peer reviewed journal
Publication Acceptance Date: 3/12/2010
Publication Date: 7/8/2010
Citation: Ma, G., Bavadekar, S.A., Schaneberg, B.T., Khan, I.A., Feller, D.R. 2010. Effects of Synephrine and B-Phenethylamine on Human a-Adrenoceptor Subtypes. Planta Medica. 76(10):981-986. Interpretive Summary: The manuscript investigated the effects of synephrine and beta-phenethylamine on apha-adrenoceptor (alpha-AR) subtypes expressed in human embroyonic kidney (HEK293) or Chinese hamster ovary (CHO) cells, and compared to that of 1R,2S-norephedrine. the results showed that synephrine acted as a partial agonist of at the alpha1-AR, while beta-Phenethylamine did not exhibit any direct agonist activity at alpha1-ar. Both, synephrine and ƒÒ-phenethylamine, may act as antagonists of pre-synaptic alpha2A/2C-ARs present in nerve terminals.
Technical Abstract: Synephrine and B-phenethylamine are structurally related to ephedrine. In this study, the effects of synephrine and B-phenethylamine are investigated on a-adrenoceptor (a-AR) subtypes expressed in human embroyonic kidney (HEK293) or Chinese hamster ovary (CHO) cells, and compared to that of 1R,2S-norephedrine. On binding assays with the a1A- and a2A-AR subtypes, the rank order of Ki values (µM) was the same for the two subtypes, viz, 1R,2S-norephedrine > B-phenethylamine > synephrine. Functional studies on the a1A-AR subtype showed that only synephrine, which possesses an aromatic 4-hydroxy group, was a partial agonist (EC50: 4 µM) giving a maximal response at 0.1 mM that was equal to 55.3% of the L-phenylephrine maximum. In contrast, neither 1R,2S-norephedrine nor B-phenethylamine exhibited agonist activity at the highest concentration tested (0.3 mM). B-Phenethylamine was slightly more potent as an antagonist than 1R,2S-norephedrine on the a1A-AR subtype. Functional studies on a2A-AR and a2C-AR subtypes in CHO cells indicated synephrine and B-phenethylamine did not act as agonists. Similar to 1R,2S -norephedrine, both of these analogs reversed the effect of medetomidine against forskolin-induced cAMP elevations at 0.3 mM. On a2A- and a2C-AR subtypes, the rank order of antagonist potency (µM) was: 1R,2S-norephedrine = B-phenethylamine > synephrine; and B-phenethylamine > 1R,2S-norephedrine > synephrine, respectively. These functional potency differences suggest that the presence of a 4-hydroxy group, as in synephrine, reduced the affinitties in these subtypes. In conclusion, at the a1-AR, synephrine acted as a partial agonist, while B-Phenethylamine did not exhibit any direct agonist activity. Both, synephrine and B-phenethylamine, may act as antagonists of pre-synaptic a2A/2C-ARs present in nerve terminals.