Adibpour Neda, Poornajjari Ali, Khodayar Mohammad Javad, Rezaee Saeed
Department of Medicinal Chemistry, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran. ; Department of Medicinal Chemistry, School of Pharmacy, Zanjan University of Medical Sciences, Zanjan, Iran. (current affiliation).
Department of Medicinal Chemistry, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.
Adv Pharm Bull. 2014;4(2):179-83. doi: 10.5681/apb.2014.026. Epub 2013 Dec 24.
The current study was designed to investigate the antinociceptive effects of several biuret derivatives with N, N-diphenyl, N-phenyl-N-alkylphenyl, N,N`-bis alkylphenyl, 2-methylquinoline-4-yl, benzo[d]thiazol-2-ylthio and (1-phenyl-1H-tetrazol-5-yl)thio substituents on the formalin-evoked pain in mice.
Antinociceptive activity of the nine biurets derivatives were assessed at different doses in mice using formalin test and the results were compared with those of indomethacin(20 mg/kg) and vehicle of the compounds. Area under the pain score curve against time (AUEC) up to 60 minutes was used as the measure of pain behavior.
A rather good analgesic effect was seen for most of the tested biuret derivatives. Significant reduction in median AUEC0-5 minutes was observed at the doses of 50 and 25 mg/kg for biurets with either benzyl and 2-methylquinoline-4-yl (C8) or phenylethyl and benzo[d]thiazol-2-ylthio(C9) moieties, respectively(p-value<0.0044). Antinociceptive activities of compound C7 (with bis phenylropyl substituent), C8 and C9 during the late phase of formaldehyde-induced pain were comparable to that of indomethacin.
Unlike indomethacin, the tested biuret compounds are able to induce antinociception in both phases of formalin test and could be considered comparable to indomethacin at the selected doses.
本研究旨在探究几种具有N,N-二苯基、N-苯基-N-烷基苯基、N,N`-双烷基苯基、2-甲基喹啉-4-基、苯并[d]噻唑-2-基硫代和(1-苯基-1H-四唑-5-基)硫代取代基的缩二脲衍生物对小鼠福尔马林诱发疼痛的抗伤害感受作用。
使用福尔马林试验评估九种缩二脲衍生物在不同剂量下对小鼠的抗伤害感受活性,并将结果与吲哚美辛(20 mg/kg)和化合物载体的结果进行比较。以60分钟内疼痛评分曲线下面积(AUEC)作为疼痛行为的衡量指标。
大多数测试的缩二脲衍生物显示出相当好的镇痛效果。分别含有苄基和2-甲基喹啉-4-基(C8)或苯乙基和苯并[d]噻唑-2-基硫代(C9)部分的缩二脲在50和25 mg/kg剂量下,0-5分钟的中位AUEC显著降低(p值<0.0044)。化合物C7(具有双苯丙基取代基)、C8和C9在甲醛诱导疼痛后期的抗伤害感受活性与吲哚美辛相当。
与吲哚美辛不同,测试的缩二脲化合物在福尔马林试验的两个阶段均能诱导抗伤害感受,并且在选定剂量下可被认为与吲哚美辛相当。