麻黃碱快速耐受性形成机制的探討

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本文对于猫瞬膜,猫及大鼠血压对麻黄碱的快速耐受性进行了系統研究。在猫对麻黄碱快速耐受性产生过程中发现:(1) 麻黄碱对瞬膜的积累作用(机率)与积累剂量(对数)呈直线关系,(2) 瞬膜对电刺激交成神经的反应减弱,(3) 血压及瞬膜对静脉注射去甲腎上腺素的反应增加。与其他实驗动物相似,大鼠連续注射麻黄碱8毫克/公斤,其升压作用也易于产生快速耐受性。大鼠血压对麻黄碱产生快速耐受性后,酪胺的剂量反应曲线被压低,但去甲腎上腺素的曲线并无显著改变。猫预先注射利血平后,其瞬膜对麻黄碱的剂量反应曲线中部(2.5毫克/公斤)被压低。在猫和大鼠的剂量-升压反应曲线中,最大也卽最后一剂麻黄碱(猫:12.5毫克/公斤;大鼠:8毫克/公斤)的反应由于快速耐受性而有所降低;但用利血平后可使这个反应较对照組显著升高。大鼠预先用不同剂量利血平后,麻黄碱快速耐受性的产生趋于延緩;并且第一剂麻黄碱的升压作用,特别是在注射利血平5毫克/公斤,3—4小时后,有增强现象。切除腎上腺对上述結果似无影响。预先灌注去甲腎上腺素也可增强第一剂麻黄碱的升压作用,但与利血平化不同,对多数大鼠,反可促进快速耐受性的产生。大鼠产生快速耐受性后,灌注去甲腎上腺素可部分地恢复麻黄碱的升压作用。预先静脉注射可卡因2.5毫克/公斤可压低麻黄碱的剂量反应曲线。以上一系列实验資料提示麻黄碱快速耐受性的形成由于两种重要因素:(1) 麻黄碱直接作用的快速耐受性是由于受体的饱和,(2) 麻黄碱间接作用的快速耐受性是由于介质的耗竭。 This paper systematically studied the rapid tolerance of ephedrine to the blood pressure of cats, cats and rats. During the cat’s rapid development of ephedrine, it was found that: (1) the cumulative effect (probability) of ephedrine on the instantaneous membrane and the accumulated dose (logarithm) showed a linear relationship; (2) Of the reaction weakened, (3) blood pressure and instantaneous membrane of intravenous injection of norepinephrine increased response. Similar to other experimental animals, rats were injected with 8 mg / kg of ephedrine continuously, and their boosting effect was also prone to rapid tolerance. The dose response curve of tyramine was depressed, but the norepinephrine curve did not change significantly after rat blood pressure was rapidly tolerated by ephedrine. After the cat was pre-injected with reserpine, the mid-portion of its ocular membrane (2.5 mg / kg) dose-response curve to ephedrine was depressed. The response of the largest dose of ephedrine to the last dose of ephedrine (cat: 12.5 mg / kg; rat: 8 mg / kg) was reduced due to rapid tolerance in dose-boost response curves in cats and rats; But after reserpine can make this response was significantly higher than the control group. Pretreatment of rats with different doses of reserpine tended to delay the onset of rapid tolerability of ephedrine; and the first dose of ephedrine was boosted, particularly at the injection of 5 mg / kg reserpine, for 3-4 hours After the increase phenomenon. Resection of the adrenal glands seems to have no effect on the above results. Pre-infusion of norepinephrine can also enhance the first dose of ephedrine boost, but unlike reserpine, for most rats, but can promote rapid tolerance. After rapid tolerance in rats, perfusion of norepinephrine partially restored the effect of ephedrine boost. A dose response curve of cocaine 2.5 mg / kg can be pre-injected intravenously with ephedrine. The above series of experimental data suggest that the rapid tolerability of ephedrine occurs due to two important factors: (1) the rapid tolerability of the direct effect of ephedrine is due to the saturation of the receptor, (2) the rapid tolerability of the indirect effect of ephedrine Sex is due to the depletion of media.
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