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Characterization of antidepressant-like effects of p-synephrine stereoisomers


We previously reported that p-synephrine has antidepressant-like activity in the murine models of forced swimming and tail suspension. In the present study, we characterized antidepressant-like effects of p-synephrine stereoisomers in both in vivo and in vitro systems. In the tail suspension test, S-(+)-p-synephrine (3 mg/kg, p.o.) reduced the duration of immobility, while R-(-)-p-synephrine (0.3–3 mg/kg, p.o.) had no effect. S-(+)-p-synephrine (0.3, 1 and 3 mg/kg, p.o.) and R-(-)-p-synephrine (1 mg/kg and 3 mg/kg, p.o.) significantly reversed the reserpine (2.5 mg/kg, i.p.)-induced hypothermia. S-(+)-p-synephrine was more effective than R-(-)-p-synephrine in inhibition of both [3H]noradrenaline uptake in rat cerebral cortical slices (maximal inhibition 85.7±7.8% vs. 59.8±4.3%; EC50 5.8±0.7 µM vs. 13.5±1.2 µM) and [3H]nisoxetine binding (K i 4.5±0.5 µM vs. 8.2±0.7 µM). In contrast, R-(-)-p-synephrine was more effective than S-(+)-p-synephrine in stimulation of [3H]noradrenaline release from rat cerebral cortical slices (maximal stimulation 23.9±1.8% vs. 20.1±1.7%; EC50 8.2±0.6 µM vs. EC50 12.3±0.9 µM). The stimulatory effect of R-(-)-p-synephrine on [3H]noradrenaline release was inhibited by nisoxetine (100 nM), but tetrodotoxin (1 µM) and elimination of extracellular calcium had no effect. It is suggested that S-(+)-p-synephrine has more effective antidepressant-like activity than R-(-)-p-synephrine.

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Kim, KW., Kim, HD., Jung, JS. et al. Characterization of antidepressant-like effects of p-synephrine stereoisomers. Naunyn-Schmied Arch Pharmacol 364, 21–26 (2001).

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  • S-(+)-p-synephrine R-(-)-p-synephrine Antidepressants Tail suspension test Reserpine [3H]Noradrenaline uptake [3H]Noradrenaline release