Evaluation of the antinociceptive activities of enaminone compounds on the formalin and hot plate tests in mice.

Willias Masocha,Ivan O Edafiogho,Samuel B Kombian

doi:10.1038/srep21582

Willias Masocha, Ivan O Edafiogho + Show 1 more

Open Access

https://doi.org/10.1038/srep21582

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Journal: Scientific Reports	Publication Date: Feb 26, 2016
Citations: 29	License type: CC BY 4.0

Affiliation: Kuwait University, University of Saint Joseph

Abstract

Recently, we found that methyl 4-(4′-bromophenyl)aminocyclohex-3-en-6-methyl-2-oxo-1-oate (E139), an anticonvulsant enaminone, has antinociceptive activity in the hot plate test. In this study we evaluated the antinociceptive activity of five anilino enaminones E139, ethyl 4-(4′-chlorophenyl)amino-6-methyl-2-oxocyclohex-3-en-1-oate (E121), ethyl 4-(4′-bromophenyl)amino-6-methyl-2-oxocyclohex-3-en-1-oate (E122), methyl 4-(4′-chlorophenyl)amino-6-methyl-2-oxocyclohex-3-en-1-oate (E138) and ethyl 4-(4′-fluorophenyl)amino-6-methyl-2-oxocyclohex-3-en-1-oate (BRG 19) using the formalin and hot plate tests. E139 has been reported to exert its effects via enhancement of extracellular GABA levels, thus tiagabine, a GABA transporter inhibitor, was evaluated as a control together with indomethacin. Tiagabine had antinociceptive activity in both phase 1 (neurogenic pain) and phase 2 (inflammatory pain) of the formalin test, whereas indomethacin had activity only in phase 2. E139 and E138 had antinociceptive activity in both phases of the formalin test, whereas E121 had activity only in phase 1 and BRG 19 had activity only in phase 2. E122 had no significant activity in either phase. In the hot plate test only E139 had antinociceptive activity. Administration of either bicuculline, a GABAA receptor antagonist, or CGP 35348, a GABAB receptor antagonist, blocked the antinociceptive activity of E139. In conclusion our results indicate that E139 has antinociceptive activity in the formalin and hot plate tests that are dependent on GABA receptors.

Highlights

E138 had antinociceptive activity in both phases of the formalin test, whereas E121 had activity only in phase 1 and BRG 19 had activity only in phase 2
We reported that E139, an anticonvulsant anilino enaminone compound, has antinociceptive activity in the hot plate test[15]
Our current study shows that E139 and E138 have antinociceptive activity in both phases of the formalin test, whereas the other enaminones tested (E121, E122 and BRG 19) were active in one phase only or did not have any activity at all

Summary

Introduction

E138 had antinociceptive activity in both phases of the formalin test, whereas E121 had activity only in phase 1 and BRG 19 had activity only in phase 2. In conclusion our results indicate that E139 has antinociceptive activity in the formalin and hot plate tests that are dependent on GABA receptors. One of the early studies published as an abstract reported analgesic, papaverine-like, and anticonvulsant activities of an enaminone compound[4]. E139 attenuated paclitaxel-induced neuropathic pain in mice and rats It had antinociceptive activity in naïve mice, in the hot plate test[15]. We evaluated the antinociceptive effects of five enaminone compounds in mice using the formalin and hot plate tests. The formalin test is used to evaluate persistent nociception caused by peripheral tissue injury and inflammation and is considered as one of the most valid models of clinical acute pain[24,25] and used for evaluation of analgesic activity of potential analgesic compounds[26,27,28]

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