Synephrine, a Component of Evodiae Fructus, Constricts Isolated Rat Aorta via Adrenergic and Serotonergic Receptors

Abstract

Abstract. We investigated the effects of Evodiae Fructus and synephrine, one of the components of Evodiae Fructus, on blood vessels. We found that Evodiae Fructus (1 × 10 −6 -3 × 10 −4 g/mL) had constrictive effects on rat aorta. The vasoconstrictive effects of Evodiae Fructus were significantly inhibited by pretreatment with prazosin (adrenergic α 1 -receptor antagonist), BRL15572 [5-hydroxytryptamine (5-HT) 1D antagonist], and ketanserin (5-HT 2A antagonist), but its vasoconstrictive effects were not inhibited by pretreatment with SB216641 (5-HT 1B antagonist) or propranolol (adrenergic β-receptor antagonist). These results suggest that Evodiae Fructus constricts rat aorta via adrenergic and serotonergic receptors. We also investigated the constrictive effects of synephrine on blood vessels. The vasoconstrictive effects of synephrine (1 × 10 −7 -3 × 10 −5 mol /L) were significantly inhibited by pretreatment with prazosin, BRL15572, and ketanserin. However, its constrictive effects were not inhibited by pretreatment with SB216641 and propranolol. The pA 2 values of prazosin or ketanserin were nearly equal between Evodiae Fructus and synephrine. Because the constrictive effects of both Evodiae Fructus and synephrine were exerted via adrenergic α 1 -receptors and serotonergic (5-HT 1D and 5-HT 2A ) receptors, synephrine may be one of the important components in the constrictive effects of Evodiae Fructus.

The Safety of Citrus aurantium (Bitter Orange) and its Primary Protoalkaloid p‐Synephrine

“…Hibino et al () assessed the ability of p ‐synephrine to constrict isolated rat aorta at concentrations of 1 × 10 ‐7 to 3 × 10 ‐5 mol/L. Using selected receptor antagonists, the authors concluded that the constrictor effects were exerted via α‐1adrenoreceptors and serotonergic (5‐HT 1D and 5‐HT 2A ) receptors.…”

A Review of the Receptor-Binding Properties ofp-Synephrine as Related to Its Pharmacological Effects

“…Based on receptor binding studies using human and animal cells, m -synephrine exerts its effects on α -  , β -1 and β -2 adrenergic receptors [28–32] resulting in increased blood pressure and heart rate effects. Jordan et al [28] compared the receptor binding activities of m - and p -synephrine and m - and p -octopamine (N-demethyl p -synephrine; Figure 8) with norepinephrine in guinea pig atria and trachea [28].…”

“…Hibino et al [32] examined the ability of p -synephrine to constrict isolated rat aorta at concentrations of 1 × 10 −7 to 3 × 10 −5  M. Using selected receptor antagonists, the authors concluded that the constrictor effects were exerted via α -1 adrenoreceptors and serotonergic (5-HT 1D and 5-HT 2A ) receptors. Again, the concentrations of p -synephrine used to produce aortic constriction were significantly higher than the peak blood levels (2 ng/mL) observed when 46.9 mg p -synephrine was given orally to human subjects and exerted little or no effect on heart rate or blood pressures [33].…”

The Action of <i>p</i>-Synephrine on Lipid Metabolism in the Perfused Rat Liver

“…[1-14 C]oleic acid (56 mCi/mmol) and [1][2][3][4][5][6][7][8][9][10][11][12][13][14] C]octanoic acid (50 mCi/mmol).…”

“…It has been shown, for example, that p-synephrine binds to serotoninergic receptors [4]. Likewise, an action of p-synephrine via adrenergic receptors has been documented [5] [6] [7]. Acute oral administration of elevated doses of a C. aurantium extract or psynephrine produced reversible toxic effects, probably due to unspecific adrenergic stimulation [3].…”