Doxapram stimulates respiratory activity through distinct activation of neurons in the nucleus hypoglossus and the pre-Bötzinger complex.
Doxapram stimulates respiratory activity through distinct activation of neurons in the nucleus hypoglossus and the pre-Bötzinger complex.
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多沙普仑通过显着激活舌下核和前 Bötzinger 复合体中的神经元来刺激呼吸活动
DOI：
10.1152/jn.00304.2018
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发表时间：
2019
影响因子：
2.5
通讯作者：
Koch H
中科院分区：
文献类型：
--
作者：
Krusynski S;Brandes J;Poets CF;Koch H
多沙普仑是一种呼吸兴奋剂，几十年来一直用作甲基黄嘌呤治疗难治性早产儿呼吸暂停的治疗选择。然而，其作用方式仍然知之甚少。我们研究了横向脑干切片制备中多沙普仑对前 Bötzinger 复合体 (PreBötC) 和下游运动输出系统舌下核 (XII) 的直接影响。虽然多沙普仑对 PreBötC 内产生的活动频率只有适度的刺激作用，但观察到 XII 中随后产生的运动输出中的群体活动幅度有更强劲的增加。在 PreBötC 和 XII 神经元的全细胞膜片钳记录中，我们证实在多沙普仑存在的情况下，XII 神经元的诱发动作电位放电显着增加，而 PreBötC 神经元的放电特性没有显着改变。有趣的是，与缺氧期间的对照条件相比，多沙普仑存在下运动输出的活动幅度没有增加。我们得出的结论是，多沙普仑的部分刺激作用是由脑干中枢的直接输入引起的，对节律生成核（PreBötC）和下游运动输出（XII）有不同的影响。新的和值得注意的临床使用的呼吸兴奋剂多沙普仑对节律生成核（前Bötzinger复合体）和运动输出中心（舌下核）有明显的影响。这些效应在缺氧期间被消除，并由舌下核神经元的固有特性和前 Bötzinger 复合体神经元接收的突触传递的明显变化介导。
Doxapram is a respiratory stimulant used for decades as a treatment option in apnea of prematurity refractory to methylxanthine treatment. Its mode of action, however, is still poorly understood. We investigated direct effects of doxapram on the pre-Bötzinger complex (PreBötC) and on a downstream motor output system, the hypoglossal nucleus (XII), in the transverse brainstem slice preparation. While doxapram has only a modest stimulatory effect on frequency of activity generated within the PreBötC, a much more robust increase in the amplitude of population activity in the subsequent motor output generated in the XII was observed. In whole cell patch-clamp recordings of PreBötC and XII neurons, we confirmed significantly increased firing of evoked action potentials in XII neurons in the presence of doxapram, while PreBötC neurons showed no significant alteration in firing properties. Interestingly, the amplitude of activity in the motor output was not increased in the presence of doxapram compared with control conditions during hypoxia. We conclude that part of the stimulatory effects of doxapram is caused by direct input on brainstem centers with differential effects on the rhythm generating kernel (PreBötC) and the downstream motor output (XII).NEW & NOTEWORTHYThe clinically used respiratory stimulant doxapram has distinct effects on the rhythm generating kernel (pre-Bötzinger complex) and motor output centers (nucleus hypoglossus). These effects are obliterated during hypoxia and are mediated by distinct changes in the intrinsic properties of neurons of the nucleus hypoglossus and synaptic transmission received by pre-Bötzinger complex neurons.
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盐酸多沙普仑呼吸刺激作用的可能作用位点。
DOI：
10.1097/00132586-196504000-00016
发表时间：
1964
期刊：
The Journal of pharmacology and experimental therapeutics
影响因子：
--
作者：
H. Kato;J. Buckley
通讯作者：
J. Buckley
影响因子：
56.9
作者：
SMITH, JC;ELLENBERGER, HH;FELDMAN, JL
通讯作者：
FELDMAN, JL
多沙普仑对新生大鼠颈动脉体分离 I 型细胞离子电流的影响
影响因子：
2.9
作者：
C. Peers
通讯作者：
C. Peers
多沙普仑在新生儿重症监护中用于治疗早产儿呼吸暂停
影响因子：
2.1
作者：
S. Prins;S. Pans;M. van Weissenbruch;F. Walther;S. Simons
通讯作者：
S. Simons
巴比妥酸盐中毒动物中新的兴奋剂的比较。
影响因子：
3.5
作者：
A. Polak;F. Plum
通讯作者：
F. Plum