Mancin A C, Soares A M, Andrião-Escarso S H, Faça V M, Greene L J, Zuccolotto S, Pelá I R, Giglio J R
Departamento de Bioquímica, Faculdade de Medicina, Universidade de São Paulo, Ribeirao Preto SP, Brazil.
Toxicon. 1998 Dec;36(12):1927-37. doi: 10.1016/s0041-0101(98)00117-2.
Crotamine, a 4.88 kDa neurotoxic protein, has been purified to apparent homogeneity from Crotalus durissus venom by gel filtration on Sephadex G-75. When injected (i.p. or s.c.) in adult male Swiss mice (20-25 g), it induced a time-dose dependent analgesic effect which was inhibited by naloxone, thus suggesting an opioid action mechanism. When compared with morphine (4 mg/kg), crotamine, even in extremely low doses (133.4 microg/kg, i.p., about 0.4% of a LD50 is approximately 30-fold more potent than morphine (w/w) as an analgesic. On a molar basis it is more than 500-fold more potent than morphine. It is also much more potent than the lower molecular weight crude fractions of the same venom. The antinociceptive effects of crotamine and morphine were assayed by the hot plate test and by the acetic acid-induced writhing method. Therefore, both central and peripheral mechanisms should be involved. Histopathological analysis of the brain, liver, skeletal muscles, stomach, lungs, spleen, heart, kidneys and small intestine of the crotamine injected mice did not show any visible lesion in any of these organs by light microscopy. Since crotamine accounted for 22% (w/w) of the desiccated venom, it was identified as its major antinociceptive low molecular weight peptide component.
克罗塔明是一种4.88千道尔顿的神经毒性蛋白，通过在葡聚糖凝胶G - 75上进行凝胶过滤，已从南美响尾蛇毒液中纯化至表观均一。当对成年雄性瑞士小鼠（20 - 25克）腹腔注射或皮下注射时，它会产生时间 - 剂量依赖性镇痛作用，且该作用被纳洛酮抑制，这表明其作用机制为阿片样物质作用机制。与吗啡（4毫克/千克）相比，即使是极低剂量的克罗塔明（133.4微克/千克，腹腔注射，约为半数致死量的0.4%）作为镇痛药的效力也比吗啡强约30倍（重量比）。以摩尔为基础计算，其效力比吗啡强500多倍。它也比同一毒液中分子量较低的粗提组分效力强得多。通过热板试验和醋酸诱导扭体法测定了克罗塔明和吗啡的抗伤害感受作用。因此，中枢和外周机制都应参与其中。对注射了克罗塔明的小鼠的脑、肝、骨骼肌、胃、肺、脾、心、肾和小肠进行组织病理学分析，通过光学显微镜观察，这些器官均未显示出任何可见病变。由于克罗塔明占干燥毒液的22%（重量比），它被确定为其主要的具有抗伤害感受作用的低分子量肽组分。
