Evaluation of the antinociceptive activities of enaminone compounds on the formalin and hot plate tests in mice.
Evaluation of the antinociceptive activities of enaminone compounds on the formalin and hot plate tests in mice.
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在福尔马林和热板测试中的磁蛋白化合物的抗伤害感受活性评估。
DOI：
10.1038/srep21582
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发表时间：
2016-02-26
影响因子：
4.6
通讯作者：
Edafiogho IO
中科院分区：
文献类型：
--
作者：
Masocha W;Kombian SB;Edafiogho IO
最近，我们发现抗惊厥药烯胺酮4-（4′-溴苯基）氨基环己-3-烯-6-甲基-2-氧代-1-酸甲酯（E139）在热板试验中具有抗伤害活性。在这项研究中，我们评价了五个苯胺基烯胺酮E139，乙基4-（4′-氯苯基）氨基-6-甲基-2-氧代环己-3-烯-1-酸酯（E121）、4-（4′-溴苯基）氨基-6-甲基-2-氧代环己-3-烯-1-酸酯（E122），4-（4′-氯苯基）氨基-6-甲基-2-氧代环己-3-烯-1-酸甲酯（E138）和4-（4′-氟苯基）氨基-6-甲基-2-氧代环己-3-烯-1-酸乙酯（BRG 19）。据报道，E139通过增强细胞外GABA水平发挥其作用，因此将GABA转运蛋白抑制剂噻加宾与吲哚美辛一起作为对照进行评价。噻加宾在福尔马林试验的第1阶段（神经源性疼痛）和第2阶段（炎性疼痛）中都具有抗伤害活性，而吲哚美辛仅在第2阶段具有活性。E139和E138在福尔马林试验的两个阶段中具有抗伤害感受活性，而E121仅在阶段1中具有活性，BRG 19仅在阶段2中具有活性。E122在这两个阶段都没有明显的活性。在热板试验中，只有E139具有抗伤害感受活性。给予荷包牡丹碱（GABAA受体拮抗剂）或CGP 35348（GABAB受体拮抗剂）可阻断E139的抗伤害活性。总之，我们的结果表明E139在福尔马林和热板测试中具有依赖于GABA受体的抗伤害活性。
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.