Research Article Uliginosin B, a Possible New Analgesic Drug, Acts by Modulating the Adenosinergic System Eveline Dischkaln Stolz, 1 Paola Fontoura da Costa, 1 Liciane Fernandes Medeiros, 2 Andressa Souza, 2 Ana Maria Oliveira Battastini, 3 Gilsane Lino von Poser, 1 Carla Bonan, 4 Iraci L. S. Torres, 2 and Stela Maris Kuze Rates 1 1 Programa de P´ os-Graduac ¸˜ ao em Ciˆ encias Farmacˆ euticas, Universidade Federal do Rio Grande do Sul, 90610-000 Porto Alegre, Brazil 2 Laborat´ orio de Farmacologia da Dor e Neuromodulac ¸˜ ao: Investigac ¸˜ oes Pr´ e-Cl´ ınicas, Departamento de Farmacologia, Instituto de Ciˆ encias B´ asicas da Sa´ ude, Universidade Federal do Rio Grande do Sul, 90046-900 Porto Alegre, Brazil 3 Departamento de Bioqu´ ımica, Instituto de Ciˆ encias B´ asicas da Sa´ ude, Universidade Federal do Rio Grande do Sul, 90035-003 Porto Alegre, Brazil 4 Laborat´ orio de Neuroqu´ ımica e Psicofarmacologia, Faculdade de Biociˆ encias, Pontifcia Universidade Cat´ olica do Rio Grande do Sul, 90619-900 Porto Alegre, Brazil Correspondence should be addressed to Stela Maris Kuze Rates; stela.rates@ufrgs.br Received 28 January 2016; Accepted 21 February 2016 Academic Editor: Vincenzo De Feo Copyright © 2016 Eveline Dischkaln Stolz et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Uliginosin B (ULI) is a natural acylphloroglucinol that has been proposed as a new molecular scafold for developing analgesic and antidepressant drugs. Its efects seem to be due to its ability to increase monoamines in the synaptic clef by inhibiting their neuronal uptake without binding to their respective transporters, but its exact mode of action is still unknown. Considering the importance of the purinergic system to pain transmission and its modulation by monoamines availability, the aim of this study was to investigate the involvement of adenosinergic signaling in antinociceptive efect of uliginosin B. Te selective adenosine A 1 receptor antagonist DPCPX and the selective A 2A antagonist ZM 241385 prevented the efect of ULI in the hot-plate test in mice. Pretreatment with inhibitors of adenosine reuptake (dipyridamole) or adenosine deaminase (EHNA) did not afect the ULI efect. On the other hand, its efect was completely prevented by an inhibitor of ecto-5  -nucleotidase (AMPCP). Tis fnding was confrmed ex vivo, whereby ULI treatment increased AMP and ATP hydrolysis in spinal cord and cerebral cortex synaptosomes, respectively. Altogether, these data indicate that activation of A 1 and A 2A receptors and the modulation of ecto-5  -nucleotidase activity contribute to the antinociceptive efect of ULI. 1. Introduction Uliginosin B (ULI) is a dimeric acylphloroglucinol consisting of flicinic acid and phloroglucinol moieties, which occurs in Hypericum species native to South America [1]. Tis molecular pattern has been proposed as a prototype to develop analgesic and antidepressant drugs [2–5]. Preclinical studies suggested that ULI has antidepressant properties, which seems to be due to its ability to increase monoamines availability in the synaptic clef by inhibiting their neuronal uptake [2]. Nevertheless, ULI does not bind to the monoamine sites on neuronal transporters, which indicates that it acts diferently from the classical antide- pressants [2]. It is noteworthy that ULI deserves attention as a drug potentially useful to reduce the dose of morphine in clinical practice [6]. Its antinociceptive efect involves the activation of monoaminergic, glutamatergic, and opioid receptors, apparently without binding to these receptors [2, 3, 5]. Terefore, other molecular targets for ULI might be considered. Te relationship between purinergic system/nociceptive pathways has been reported [7]; numerous studies described the interaction between purinergic, monoaminergic, and opioid pathways [8–14]. Hindawi Publishing Corporation Evidence-Based Complementary and Alternative Medicine Volume 2016, Article ID 5890590, 8 pages http://dx.doi.org/10.1155/2016/5890590