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Effects of NMDA receptor antagonists on opioid-induced respiratory depression and acute antinociception in rats.

机译:NMDA受体拮抗剂对阿片类药物引起的呼吸抑制和急性镇痛作用的影响。

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Although exogenous opioids alter the responses of animals to tissue-damaging stimuli and therefore are the cornerstone in the treatment of acute antinociception, they have profound side effects on ventilation. To diminish ventilatory effects, combination therapies have been advocated. Recent studies reported the effectiveness of the addition of N-methyl-D-aspartate (NMDA) receptor antagonists such as ketamine to morphine in the treatment of acute pain. However, NMDA receptors, together with non-NMDA receptors are known to be involved in the neurotransmission of inspiratory drive to phrenic motoneurons. Co-administration of NMDA and non-NMDA receptor antagonists has been shown to be deleterious to respiratory function. The present study investigated the hypothesis that the association of opioids and NMDA receptor antagonists may add to the impairment of respiratory parameters. In male Wistar rats, combinations of opioids (fentanyl or morphine) at antinociceptive doses and NMDA receptor antagonists (ketamine, 40 mg/kg, or dextromethorphan, 10 mg/kg) at subanesthetic doses were administered intraperitoneally. Antinociception was tested with the tail-withdrawal reaction (TWR) test, while the effect on respiratory parameters was investigated with blood-gas analysis.We found that, in rats, co-administration of NMDA receptor antagonists and opioids may result in an increased respiratory depression as compared to the opioids alone. The effect of the NMDA receptor antagonists on opioid-induced antinociception was limited.
机译:尽管外源阿片类药物改变动物对组织破坏性刺激的反应,因此是治疗急性镇痛作用的基石,但它们对通气具有深远的副作用。为了减少通气效果,已提倡联合疗法。最近的研究报道了在吗啡中添加N-甲基-D-天冬氨酸(NMDA)受体拮抗剂(如氯胺酮)可有效治疗急性疼痛。然而,已知NMDA受体与非NMDA受体一起参与向drive运动神经元的吸气驱动的神经传递。已经显示NMDA和非NMDA受体拮抗剂的共同给药对呼吸功能有害。本研究调查了阿片类药物和NMDA受体拮抗剂可能加重呼吸参数损害的假说。在雄性Wistar大鼠中,腹腔内给药亚镇痛剂量的阿片类药物(芬太尼或吗啡)与NMDA受体拮抗剂(氯胺酮40 mg / kg或右美沙芬10 mg / kg)的组合。通过尾巴抽出反应(TWR)测试抗伤害感受,同时通过血气分析研究其对呼吸参数的影响。我们发现,在大鼠中,NMDA受体拮抗剂和阿片类药物的共同给药可能导致呼吸增加与仅使用阿片类药物相比抑郁症。 NMDA受体拮抗剂对阿片类药物诱导的抗伤害感受的作用是有限的。

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