Abstract
The antinociceptive effects produced by intraperitoneal administration of a novel synthetic chalcone, 3-(2,3-dimethoxyphenyl)-1-(5-methylfuran-2-yl)prop-2-en-1-one (DMFP), were investigated in several mouse models of induced nociception. The administration of DMFP (0.1, 0.5, 1.0 and 5.0 mg/kg) produced significant attenuation on the acetic acid-induced abdominal-writhing test. It also produced a significant increase in response latency time in the hot-plate test and a marked reduction in time spent licking the injected paw in both phases of the formalin-induced paw-licking test. In addition, it was also demonstrated that DMFP exhibited significant inhibition of the neurogenic nociceptive response induced by intraplantar injections of capsaicin and glutamate. Moreover, the antinociceptive effect of DMFP in the acetic acid-induced abdominal-writhing test and the hot-plate test was not antagonized by pretreatment with a non-selective opioid receptor antagonist, naloxone. Finally, DMFP did not show any toxic effects and/or mortality in a study of acute toxicity and did not interfere with motor coordination during the Rota-rod test. Our present results show that DMFP exhibits both peripheral and central antinociceptive effects. It was suggested that its peripheral antinociceptive activity is associated with attenuated production and/or release of NO and various pro-inflammatory mediators, while central antinociceptive activity seems to be unrelated to the opioidergic system, but could involve, at least in part, an interaction with the inhibition of capsaicin-sensitive fibers and the glutamatergic system.
Highlights
Pain remains a major issue in a vast array of medical conditions
It was suggested that the introduction of acetic acid into the peritoneal cavity induces nociception by directly activating non-selective cationic channels located in the primary afferent pathways or indirectly by promoting the release of various endogenous algesic mediators such as prostaglandins, cytokines, bradykinin and others, as well as increasing lipoxygenase (LOX) and cyclooxygenase (COX) production in peripheral tissues [23,24,25,26]
The findings of the present study indicate that the administration (i.p.) of DMFP produced a significant dose-dependent reduction in the amount of abdominal writhing induced by acetic acid as compared to the control group
Summary
Pain remains a major issue in a vast array of medical conditions. many effective and potent pharmacotherapies such as opioids and non-steroidal anti-inflammatory analgesic drugs are available, they all have limitations. The search for new analgesic compounds with good efficacy and least undesirable side effects to alleviate this obstinate painful condition is potentially very. Molecules 2016, 21, 1077 important and is an interesting strategy Taking these into consideration, compounds showing an analgesic effect have appeared as attractive therapeutic sources for the development of new relevant drugs for the management of several painful conditions. Chalcones (1,3-diaryl-2-propen-1-ones) represent an important group of natural or synthetic compounds belonging to the flavonoid family. They have been reported to exhibit broad spectrum of biological and pharmacological activities, such as antimicrobial [4], anticancer [5], antiulcer [6], important is an interesting [10], strategy
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