7-hydroxymitragynine, a constituent of the Thai herbal medicine Mitragyna speciosa, has been found to have a potent opioid antinociceptive effect. In the present study, we investigated the mechanism of antinociception and the inhibitory effect on gastrointestinal transit of 7-hydroxymitragynine, and compared its effects with those of morphine. When administered subcutaneously to mice, 7-hydroxymitragynine produced antinociceptive effects about 5.7 and 4.4 times more potent than those of morphine in the tail-flick (ED50=0.80 mg/kg) and hot-plate (ED50=0.93 mg/kg) tests, respectively. The antinociceptive effect of 7-hydroxymitragynine was significantly blocked by the mu1/mu2-opioid receptor antagonist beta-funaltrexamine hydrochloride (beta-FNA) and the mu1-opioid receptor-selective antagonist naloxonazine in both tests. Thus, 7-hydroxymitragynine acts predominantly on mu-opioid receptors, especially on mu1-opioid receptors. Isolated tissue studies further supported its specificity for the mu-opioid receptors. Further, 7-hydroxymintragynine dose-dependently (ED50=1.19 mg/kg, s.c.) and significantly inhibited gastrointestinal transit in mice, as morphine does. The inhibitory effect was significantly antagonized by beta-FNA pretreatment, but slightly antagonized by naloxonazine. The ED50 value of 7-hydroxymitragynine on gastrointestinal transit was larger than its antinociceptive ED50 value. On the other hand, morphine significantly inhibits gastrointestinal transit at a much smaller dose than its antinociceptive dose. These results suggest that mu-opioid receptor mechanisms mediate the antinociceptive effect and inhibition of gastrointestinal transit. This compound induced more potent antinociceptive effects and was less constipating than morphine.

译文

7-hydroxyymyramynine,泰国草药mitramyna speciosa的一种成分,已被发现具有有效的阿片类药物抗伤害作用。在本研究中,我们研究了7-羟基雌米雌酮的抗伤害感受机制和对胃肠道转运的抑制作用,并将其与吗啡的作用进行了比较。当皮下给药小鼠时,在甩尾 (ED50 = 0.80 mg/kg) 和热板 (ED50 = 0.93 mg/kg) 测试中,7-羟基肌酸产生的抗伤害感受作用比吗啡的作用强约5.7和4.4倍。在两次测试中,mu1/mu2-opioid受体拮抗剂 β-氟曲胺盐酸盐 (β-FNA) 和mu1-opioid受体选择性拮抗剂纳洛酮嗪均显着阻断了7-羟基酪氨酸的抗伤害感受作用。因此,7-羟甲基主要作用于 μ-阿片受体,尤其是mu1-opioid受体。孤立的组织研究进一步支持了其对 μ 阿片受体的特异性。此外,7-羟基喹啉呈剂量依赖性 (ED50 = 1.19 mg/kg,s.C.),并显著抑制小鼠的胃肠转运,如吗啡。Β-FNA预处理可显着拮抗抑制作用,但纳洛酮嗪可轻微拮抗。7-羟基雌杆菌在胃肠道运输中的ED50值大于其抗伤害感受ED50值。另一方面,吗啡以比其抗伤害感受剂量小得多的剂量显着抑制胃肠道转运。这些结果表明,μ 阿片受体机制介导了抗伤害感受作用和抑制胃肠道转运。与吗啡相比,该化合物可产生更有效的抗伤害感受作用,并且便秘更少。

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