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 microM vs. 13.5 +/- 1.2 microM) and [3H]nisoxetine binding (Ki 4.5 +/- 0.5 microM vs. 8.2 +/- 0.7 microM). 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 microM vs. EC50 12.3 +/- 0.9 microM). The stimulatory effect of R-(-)-p-synephrine on [3H]noradrenaline release was inhibited by nisoxetine (100 nM), but tetrodotoxin (1 microM) 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.
Kim
K W
KW
Department of Pharmacology, Chonbuk National University Medical School, Institute for Medical Sciences, Chonchu, South Korea.
Kim
H D
HD
Jung
J S
JS
Woo
R S
RS
Kim
H S
HS
Suh
H W
HW
Kim
Y H
YH
Song
D K
DK
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D000928:Antidepressive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects; D005473:Fluoxetine / Q000031:analogs & derivatives* / Q000494:pharmacology; D019417:Hindlimb Suspension; D007035:Hypothermia; D066298:In Vitro Techniques; D008297:Male; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D012110:Reserpine / Q000494:pharmacology; D013237:Stereoisomerism; D013550:Swimming; D013578:Synephrine / Q000008:administration & dosage / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology; D014316:Tritium
D018759:Adrenergic Uptake Inhibitors; D000316:Adrenergic alpha-Agonists; D000779:Anesthetics, Local; D000928:Antidepressive Agents; D005473:Fluoxetine; D014316:Tritium; C011386:nisoxetine; D013779:Tetrodotoxin; D012110:Reserpine; D013578:Synephrine; D009638:Norepinephrine