【摘 要】
：
The first-generation antihistamines are widely prescribed medications to relieve allergic reactions and urticaria by blocking the peripheral histamine H1 receptor.Overdose of these drugs often results
【机 构】
：
Department of Pharmacology, Hebei Medical University; Shijiazhuang 050017, China
【出 处】
：
中国神经科学学会第四次会员代表大会暨第七届全国学术会议(The 7th Biennial Meeting and the
论文部分内容阅读
The first-generation antihistamines are widely prescribed medications to relieve allergic reactions and urticaria by blocking the peripheral histamine H1 receptor.Overdose of these drugs often results in serious neuronal toxic effects,including seizures,convulsions and worsening of epileptic symptoms.Till now,the molecular mechanism underlying these adverse effects has not been fully understood.KCNQ/M K+ channel plays a crucial role in controlling neuron excitability.Here,we demonstrate that mepyramine and diphenhydrarnine,two structurally related first-generation antihistamines,can act as potent KCNQ/M channel blockers.Extracellular application of these drugs quickly and reversibly reduced KCNQ2/Q3 currents heterologously expressed in HEK293 cells.The current inhibition was concentration and voltage dependent.The estimated IC50 (12.5 and 48.1 μmol/L,respectively) is within the scope of drug concentrations detected in poisoned patients (30 to 300 μmol/L).Both drugs shifted the Ⅰ-Ⅴ curve of KCNQ2/Q3 channel to more depolarized potentials,and altered channel gating property by prolonging activation and shortening deactivation kinetics.
其他文献
Internalization and sorting of agonist-stimulated receptors between divergent recycling and degradative membrane pathway are critical events determining the functional consequences of p-opioid recepto
Objective We sought to characterize the brain responses and structure of patients with acute severe post traumatic stress disorder (PTSD),and investigate the neurocircuit of PTSD.All subjects would be
Objective Angiogenesis and inflammation are induced immediately after cerebral ischemia,and play a pivotal role in the strategy against ischemic injury.Their molecular mechanisms in the ischemic brain
This study aimed to develop a cell culture model of Huntington disease and observe the effect of sodium butyrate on this cell culture model.Exon 1 of both a wild type and a mutant IT15 gene from the g
Cerebral infarction is a common and frequently encountered disease,which is mostly onset in people after middle age.For its severe complications and high ratios of disability and mortality,peoples hea
周围神经损伤是指因某些因素造成神经传导功能障碍、神经轴索中断或神经断裂，导致躯干和四肢感觉、运动、交感功能障碍的一类临床病症，它严重影响患者的劳动力和生活质量。损伤后的再生修复问题一直是创伤外科和神经科学关注的重点之一。周围神经损伤后，损伤平面远段的神经纤维全长以及近段发生长度不等的髓鞘和轴突崩解破坏，即华勒氏变性。随后损伤近段的轴突出芽、延伸，长入远端雪旺氏细胞索，使再生轴突再髓鞘化，从而与相应
In the present study,the effects of Ginsenoside Rg1 (Rg1) on 1-methy-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced dopamineregic neuron degeneration in the substantia nigra (SN) of C57BL6 mice we
老年性痴呆(Alzheimers disease,AD)是常见的中枢神经变性疾病,其确切的病因不清.以往研究线索表明,AD患者基底前脑胆碱能神经元死亡明显,而兴奋性毒性损伤是导致神经元损伤与AD发病的重要因素.本课题采用kainic acid (KA)兴奋性毒性动物模型,给予神经激肽NK1、NK3受体特异性激动剂(septide、senktide),NK3受体拮抗剂(SB218795)干预和Flu
The degradation of aberrantly phosphorylated tau in neurons plays an important role in the pathogenesis of Alzheimers disease (AD).hHrd1 is a newly identified ubiquitin ligase involved in the endoplas
Objective Previously we have demonstrated that cyclothiazide (CTZ) could induce epilepitiform activity in hippocampal neurons both in vitro and in vivo.Here,we further report that CTZ dose-dependently