AMPA receptor competitive antagonism reduces halothane MAC in rats.

AMPA receptor competitive antagonism reduces halothane MAC in rats.
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AMPA 受体竞争性拮抗作用可降低大鼠中的氟烷 MAC。

DOI:
10.1097/00000542-199212000-00018
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发表时间:
1992
期刊:
影响因子:
8.8
通讯作者:
Nordholm,L
Nordholm,L
中科院分区:
医学1区
文献类型:
--
作者:
McFarlane,C;Warner,DS;Todd,MM;Nordholm,L

文献摘要

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谷氨酸(一种兴奋性神经递质)的受体有多种亚型。先前的研究表明,谷氨酸对 NMDA 受体的拮抗作用会降低挥发性麻醉剂的最低肺泡浓度 (MAC)。 NBQX (2, 3-二羟基-6-硝基-7-氨磺酰基-苯并(f)喹喔啉) 是谷氨酸能 AMPA 受体的选择性拮抗剂。本实验的目的是确定 AMPA 受体拮抗作用是否影响大鼠中的氟烷 MAC。 Sprague-Dawley大鼠在50% O2/平衡N2中用氟烷麻醉,气管插管并对肺进行机械通气。三组静脉输注增加剂量的 NBQX,而对照组输注载体(D5W)。然后通过尾夹法测定氟烷 MAC。氟烷 MAC 与血浆 NBQX 浓度呈对数线性相关(MAC= 0.125(血浆浓度 NBQX)+ 1.035,r2= 0.77)。 NBQX 负荷剂量为 42 mg/kg,随后连续输注率为 36 mg x kg-1 x h-1,氟烷 MAC 最大减少 58%(对照= 1.02+/-0.07%;NBQX= 0.43+/-0.12%;P<.01)。由于该化合物的水溶性较差,因此不可能使用更大剂量的 NBQX。在另一项实验中,清醒的大鼠根据 NBQX 输注剂量被随机分组​​。在 NBQX 输注开始后的第 0 分钟以及第 5 分钟和第 30 分钟测量 Pa (CO2) 和平均动脉压。然后停止输注。记录翻正反射恢复所需的时间。(摘要截短为 250 字)
Various subtypes of receptors have been identified for glutamate, an excitatory neurotransmitter. Previous studies have shown that antagonism of glutamate at the NMDA receptors reduces minimum alveolar concentration (MAC) for volatile anesthetics. NBQX (2, 3-dihydroxy-6-nitro-7-sulfamoyl-benzo (f) quinoxaline) is a selective antagonist at the glutamatergic AMPA receptor. The purpose of this experiment was to determine whether AMPA receptor antagonism influences halothane MAC in the rat. Sprague-Dawley rats were anesthetized with halothane in 50% O2/balance N2, tracheally intubated and the lungs were mechanically ventilated. Increasing doses of NBQX were intravenously infused in three groups while the control group was infused with vehicle (D5W). Halothane MAC was then determined by the tail-clamp method. Halothane MAC was log-linearly related to plasma NBQX concentrations (MAC= 0.125 (In plasma concentration NBQX)+ 1.035, r2= 0.77). A maximal 58% reduction of halothane MAC was achieved with an NBQX loading dose of 42 mg/kg followed by a continuous infusion rate of 36 mg x kg-1 x h-1 (control= 1.02+/-0.07%; NBQX= 0.43+/-0.12%; P<. 01). Larger doses of NBQX were not possible because of the poor aqueous solubility of this compound. In a separate experiment, awake rats were randomly assigned to groups based on the dose of NBQX infused. Pa (CO2) and mean arterial pressure were measured at time 0 and at 5 and 30 min after start of NBQX infusion. The infusion was then stopped. Time until recovery of the righting reflex was recorded.(ABSTRACT TRUNCATED AT 250 WORDS)