Objective: Investigate the involvement of monoaminergic and glutamatergic systems on the antinociceptive and ataxic effects of uliginosin B, which we have already demonstrated to be a promising molecular scaffold to develop new analgesic drugs.
Methods: Uliginosin B was obtained from hexane extract of aerial parts of Hypericum polyanthemum by chromatographic methods. Uliginosin B antinociceptive and motor coordination effects were evaluated in mice by using hot-plate (15 and 90 mg/kg, i.p.) and rotarod (90 mg/kg, i.p.) tests, respectively. The mechanism of action was investigated through pretreatments with prazosin 1 mg/kg intraperitoneal (α1 receptor antagonist), yohimbine 5 mg/kg intraperitoneal (α2 receptor antagonist), pCPA 300 mg/kg intraperitoneal (serotonin synthesis inhibitor) and MK-801 0.25 mg/kg intraperitoneal (N-methyl-D-aspartic acid receptor antagonist).
Key findings: The antinociceptive effect of uliginosin B (15 and 90 mg/kg, i.p.) was reduced significantly by pCPA and MK-801. Prazosin and yohimbine improved the antinociceptive effect of the highest dose (90 mg/kg, i.p.) of uliginosin B only. The ataxic effect of uliginosin B (90 mg/kg, i.p.) was completely prevented by pretreatment with pCPA or MK-801, but it was unaffected by pretreatment with prazosin or yohimbine.
Conclusion: These data confirm the contribution of monoaminergic neurotransmission as well as provide the first evidence of glutamatergic neurotransmission contribution to the uliginosin B effects.
Keywords: Hypericum; monoaminergic neurotransmission; antinociceptive; glutamatergic neurotransmission; phloroglucinol.
© 2014 Royal Pharmaceutical Society.