Synergistic effect of the l-tryptophan and kynurenic acid with dipyrone or paracetamol in mice

详细信息    查看全文

• 作者：Nayrton Fl¨¢vio Moura Rocha ; Emiliano Ricardo Vasconcelos Rios ; Alyne Mara Rodrigues Carvalho ; Leonardo Vasconcelos Freire ; Mar¨ªlia Leite Dias ; Marta Maria de Fran?a Fonteles ; Francisca Cl¨¦a Floren?o de Sousa
• 关键词：Dipyrone ; Paracetamol ; l-Tryptophan ; Kynurenic acid ; Nociception ; Synergism
• 刊名：Chemico-Biological Interactions
• 出版年：2013
• 出版时间：25 September, 2013
• 年：2013
• 卷：205
• 期：2
• 页码：148-156
• 全文大小：1065 K

文摘

Purpose

Our great interest in this work was study the synergism between l-tryptophan and dipyrone or paracetamol as well as the interaction of kynurenic acid (l-tryptophan metabolite) and these analgesics agents utilizing a robust methodology.

Methods

We performed the writhing test induced by acetic acid in mice to evaluate the antinociceptive effect of the treatments isolated and combined (p.o. and i.p.). Dose-response curves were constructed and the values of ED₅₀ for treatment alone and combined were statistically compared. In addition, isobolographic analysis was performed and the experimental values were compared with the theoretical values for simple additive effect.

Results

The combined treatment with l-tryptophan and dipyrone or paracetamol reduced significantly the ED₅₀ of these analgesics when compared to the isolated treatments. l-tryptophan alone has no antinociceptive effect. l-Tryptophan increases the central amount of 5-HT and the synergism with dipyrone is antagonized by the 5-HT depletion. The kyna has an antinociceptive dose-related effect and a synergistic interaction with dipyrone and paracetamol verified by isobolographic analyses and confirmed by experimental values of ED₅₀ of combined treatments were statistically lower than theoretical calculated values for simple additive effect. Melatonin antagonist receptor attenuates the antinociceptive synergism between l-tryptophan and dipyrone.

Conclusion

Our results demonstrate that the increased 5-HT amount on the central nervous system is not per se capable to induce antinociception. The l-tryptophan interacts synergistically with dipyrone and paracetamol both orally and by i.p. route. This effect is dependent on the biotransformation of l-tryptophan to 5-HT and involves kynurenic acid and melatonin receptors.