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氟硝西泮增强大鼠酒精的抑制作用:一项脑电图、呼吸和心电图研究。

Potentiation of the depressant effect of alcohol by flunitrazepam in rats: an electrocorticographic, respiratory and electrocardiographic study.

机构信息

Laboratory of Pharmacology and Toxicology of Natural Products, Biological Science Institute, Federal University of Pará, Belém, Brazil.

Laboratory of Experimental Neuropathology, Biological Science Institute, Federal University of Pará, Belém, Brazil.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2024 Oct;397(10):7599-7613. doi: 10.1007/s00210-024-03111-w. Epub 2024 Apr 27.

Abstract

Alcohol, a widely commercialized psychotropic drug, and the benzodiazepine Flunitrazepam, an anxiolytic widely prescribed for patients with anxiety and insomnia problems, are well known drugs and both act on the central nervous system. The misuse and the association of these two drugs are public health concerns in several countries and could cause momentary, long-lasting and even lethal neurophysiological problems due to the potentiation of their adverse effects in synergy. The present study observed the result of the association of these drugs on electrophysiological responses in the brain, heart, and respiratory rate in Wistar rats. 8 experimental groups were determined: control, one alcohol group (20% at a dose of 1 ml/100 g VO), three Flunitrazepam groups (doses 0.1; 0.2 and 0.3 mg/kg) and three alcohol-Flunitrazepam groups (20% at a dose of 1 ml/100 g VO of alcohol, combined with 0.1; 0.2 and 0.3 mg/kg of Flunitrazepam, respectively). The results showed that there was a more pronounced reduction in alpha and theta wave power in the alcohol-Flunitrazepam groups, a decrease in the power of beta oscillations and greater sedation. There was a progressive decrease in respiratory rate linked to the increase of Flunitrazepam dose in the alcohol-Flunitrazepam associated administration. It was observed alteration in heart rate and Q-T interval in high doses of Flunitrazepam. Therefore, we conclude that the association alcohol-Flunitrazepam presented deepening of depressant synergistic effects according to the increase in the dose of the benzodiazepine, and this could cause alterations in low frequency brain oscillations, breathing, and hemodynamics of the patient.

摘要

酒精是一种广泛商业化的精神药物,苯二氮䓬类药物氟硝西泮是一种广泛用于治疗焦虑和失眠问题的抗焦虑药,这两种药物都作用于中枢神经系统。这两种药物的滥用和联合使用是许多国家的公共卫生关注点,由于它们的不良反应协同作用,可能会导致暂时的、长期的甚至致命的神经生理问题。本研究观察了这两种药物联合使用对 Wistar 大鼠大脑、心脏和呼吸频率的电生理反应的结果。确定了 8 个实验组:对照组、一个酒精组(20%,剂量为 1ml/100gVO)、三个氟硝西泮组(剂量分别为 0.1、0.2 和 0.3mg/kg)和三个酒精-氟硝西泮组(20%,剂量为 1ml/100gVO 酒精,分别与 0.1、0.2 和 0.3mg/kg 的氟硝西泮联合使用)。结果表明,酒精-氟硝西泮组的 alpha 和 theta 波功率下降更为明显,beta 振荡的功率下降,镇静作用增强。随着酒精-氟硝西泮联合用药中氟硝西泮剂量的增加,呼吸频率呈渐进性下降。观察到高剂量氟硝西泮时心率和 Q-T 间期的改变。因此,我们得出结论,随着苯二氮䓬类药物剂量的增加,酒精-氟硝西泮联合使用呈现出更深的抑制协同作用,这可能导致患者大脑低频振荡、呼吸和血液动力学的改变。

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