Prokopp C R, Rubin M A, Sauzem P D, de Souza A H, Berlese D B, Lourega R V, Muniz M N, Bonacorso H G, Zanatta N, Martins M A P, Mello C F
Laboratório de Neurotoxicidade e Psicofarmacologia, Departamento de Química, Setor de Bioquímica, Centro de Ciências Naturais e Exatas, Universidade Federal de Santa Maria, RS, Brasil.
Braz J Med Biol Res. 2006 Jun;39(6):795-9. doi: 10.1590/s0100-879x2006000600013. Epub 2006 Jun 2.
The present study investigates the antinociceptive effect of the pyrazolyl-thiazole derivative 2-(5-trichloromethyl-5-hydroxy-3-phenyl-4,5-dihydro-1H-pyrazol-1-yl)-4-(4-bromophenyl)-5-methylthiazole (B50) in mice. Male albino Swiss mice (30-40 g) were used in the acetic acid-induced abdominal writhes and tail-immersion tests. B50 caused dose-dependent antinociception (8, 23 and 80 micromol/kg, s.c.) in the acetic acid writhing assay (number of writhes: vehicle: 27.69 +/- 6.15; B50 (8 micromol/kg): 16.92 +/- 3.84; B50 (23 micromol/kg): 13.85 +/- 3.84; B50 (80 micromol/kg): 9.54 +/- 3.08; data are reported as means +/- SEM for 9 animals per group). On the other hand, B50 did not cause antinociception in the tail immersion assay. Naloxone (2.75 micromol/kg, s.c.) prevented B50-induced antinociception (number of writhes: vehicle-saline: 31.11 +/- 3.15; vehicle-naloxone: 27.41 +/- 3.70; B50 (80 micromol/kg)-saline: 8.70 +/- 3.33; B50 (80 micromol/kg)-naloxone: 31.84 +/- 4.26; morphine-saline: 2.04 +/- 3.52; morphine-naloxone: 21.11 +/- 4.26; 8-9 animals per group). The removal of the methyl group of the thiazole ring of B50 or substitution of the bromo substituent with the methyl at position 4 of the phenyl group, which is attached to the thiazole ring of B50, resulted in loss of activity, suggesting that these substituents are important for antinociceptive activity. B50 had no effect on spontaneous locomotion or rotarod performance, indicating that the antinociceptive effect of B50 is not related to nonspecific motor effects. The antinociceptive profile of B50 seems to be closer to nonsteroidal anti-inflammatory drugs than to classic opioid agents, since it had no analgesic effect in a thermally motivated test.
本研究考察了吡唑基噻唑衍生物2-(5-三氯甲基-5-羟基-3-苯基-4,5-二氢-1H-吡唑-1-基)-4-(4-溴苯基)-5-甲基噻唑（B50）对小鼠的抗伤害感受作用。雄性白化瑞士小鼠（30 - 40克）用于醋酸诱导的扭体试验和尾部浸入试验。在醋酸扭体试验中，B50产生剂量依赖性抗伤害感受作用（皮下注射8、23和80微摩尔/千克）（扭体次数：溶剂对照组：27.69±6.15；B50（8微摩尔/千克）：16.92±3.84；B50（23微摩尔/千克）：13.85±3.84；B50（80微摩尔/千克）：9.54±3.08；数据以每组9只动物的平均值±标准误表示）。另一方面，B50在尾部浸入试验中未产生抗伤害感受作用。纳洛酮（皮下注射2.75微摩尔/千克）可阻断B50诱导的抗伤害感受作用（扭体次数：溶剂-生理盐水组：31.11±3.15；溶剂-纳洛酮组：27.41±3.70；B50（80微摩尔/千克）-生理盐水组：8.70±3.33；B50（80微摩尔/千克）-纳洛酮组：31.84±4.26；吗啡-生理盐水组：2.04±3.52；吗啡-纳洛酮组：21.11±4.26；每组8 - 9只动物）。去除B50噻唑环上的甲基或用甲基取代与B50噻唑环相连的苯基4位上的溴取代基，会导致活性丧失，这表明这些取代基对抗伤害感受活性很重要。B50对自发运动或转棒试验表现无影响，表明B50的抗伤害感受作用与非特异性运动效应无关。B50的抗伤害感受特征似乎更接近非甾体抗炎药而非经典阿片类药物，因为它在热刺激试验中无镇痛作用。
