Characterization of antidepressant-like effects of p-synephrine stereoisomers

Abstract

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 [H-3]noradrenaline uptake in rat cerebral cortical slices (maximal inhibition 85.7 +/-7.8% vs. 59.8 +/-4.3%; EC50 5.8 +/-0.7 muM vs. 13.5 +/-1.2 muM) and [H-3]nisoxetine binding (K-i 4.5 +/-0.5 muM vs. 8.2 +/-0.7 muM). In contrast, R-(-)-p-synephrine was more effective than S-(+)-p-synephrine in stimulation of [H-3]noradrenaline release from rat cerebral cortical slices (maximal stimulation 23.9 +/-1.8% vs. 20.1 +/-1.7%; EC50 8.2 +/-0.6 muM vs. EC50 12.3 +/-0.9 muM). The stimulatory effect of R-(-)-p-synephrine on [H-3]noradrenaline release was inhibited by nisoxetine (100 nM), but tetrodotoxin (1 muM) 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.