氯美噻唑对大鼠脑内GABAA受体复合物的调节作用
The modulation by chlormethiazole of the GABAA-receptor complex in rat brain.
作者信息
Cross A J, Stirling J M, Robinson T N, Bowen D M, Francis P T, Green A R
机构信息
Astra Neuroscience Research Unit, Institute of Neurology, London.
出版信息
Br J Pharmacol. 1989 Sep;98(1):284-90. doi: 10.1111/j.1476-5381.1989.tb16893.x.
Abstract
- The interactions of chlormethiazole with gamma-aminobutyric acid (GABA) synthesis and release, and with ligand binding to sites associated with the GABAA-receptor complex and the GABAB-receptor have been studied in the rat. The GABAA-receptor was studied using [3H]-muscimol, [3H]-flunitrazepam was used to label the benzodiazepine modulatory site, and [35S]-butyl-bicyclophosphorothionate ([35S]-TBPS) to label the chloride channel. 2. Chlormethiazole had no effect on GABA synthesis in the cortex, hippocampus and striatum or on GABA release from cortical slices in vitro. Chlormethiazole did not displace [3H]-baclofen binding to the GABAB-receptor. 3. Chlormethiazole (IC50 = 140 microM) and pentobarbitone (IC50 = 95 microM) both inhibited [35S]-TBPS binding by increasing the rate of [35S]-TBPS dissociation. In addition, chlormethiazole caused an apparent decrease in the affinity of [35S]-TBPS binding. 4. Chlormethiazole enhanced the binding of [3H]-muscimol but had no effect on [3H]-flunitrazepam binding. In contrast, the sedative barbiturate pentobarbitone enhanced both [3H]-muscimol and [3H]-flunitrazepam binding. 5. It is concluded that the sedative and anticonvulsant effects of chlormethiazole are probably mediated through an action at the GABAA-receptor. However, chlormethiazole does not interact with the GABAA-receptor complex in an identical manner to the sedative barbiturate pentobarbitone.
摘要
- 已在大鼠中研究了氯美噻唑与γ-氨基丁酸（GABA）合成及释放的相互作用，以及与GABAA受体复合物和GABAB受体相关位点的配体结合情况。使用[3H]-蝇蕈醇研究GABAA受体，用[3H]-氟硝西泮标记苯二氮䓬调节位点，用[35S]-丁基双环磷硫代酸盐（[35S]-TBPS）标记氯离子通道。2. 氯美噻唑对皮质、海马体和纹状体中的GABA合成或体外皮质切片中的GABA释放均无影响。氯美噻唑不取代[3H]-巴氯芬与GABAB受体的结合。3. 氯美噻唑（IC50 = 140微摩尔）和戊巴比妥（IC50 = 95微摩尔）均通过增加[35S]-TBPS解离速率来抑制[35S]-TBPS结合。此外，氯美噻唑使[35S]-TBPS结合的亲和力明显降低。4. 氯美噻唑增强了[3H]-蝇蕈醇结合，但对[3H]-氟硝西泮结合无影响。相比之下，镇静性巴比妥类药物戊巴比妥增强了[3H]-蝇蕈醇和[3H]-氟硝西泮的结合。5. 得出结论，氯美噻唑的镇静和抗惊厥作用可能是通过作用于GABAA受体介导的。然而，氯美噻唑与GABAA受体复合物的相互作用方式与镇静性巴比妥类药物戊巴比妥不同。
相似文献
1
The modulation by chlormethiazole of the GABAA-receptor complex in rat brain.氯美噻唑对大鼠脑内GABAA受体复合物的调节作用
Br J Pharmacol. 1989 Sep;98(1):284-90. doi: 10.1111/j.1476-5381.1989.tb16893.x.
2
A behavioural and neurochemical study in rats of the pharmacology of loreclezole, a novel allosteric modulator of the GABAA receptor.一项关于新型GABAA受体变构调节剂氯雷唑药理作用的大鼠行为学和神经化学研究。
Neuropharmacology. 1996;35(9-10):1243-50. doi: 10.1016/s0028-3908(96)00060-3.
3
The human neuroblastoma cell line, IMR-32 possesses a GABAA receptor lacking the benzodiazepine modulatory site.人神经母细胞瘤细胞系IMR - 32拥有一种缺乏苯二氮䓬调节位点的GABAA受体。
Neuropharmacology. 1993 May;32(5):455-60. doi: 10.1016/0028-3908(93)90169-4.
4
Studies on picrotoxin binding sites of GABAA receptors in rat cortical synaptoneurosomes.大鼠皮质突触神经小体中γ-氨基丁酸A型受体的印防己毒素结合位点研究
Brain Res Bull. 1994;33(4):373-8. doi: 10.1016/0361-9230(94)90279-8.
5
6
7
Biochemical evaluations of the effects of loreclezole and propofol on the GABAA receptor in rat brain.洛雷唑和丙泊酚对大鼠脑内GABAA受体作用的生化评估。
Biochem Pharmacol. 1996 Jun 14;51(11):1527-34. doi: 10.1016/0006-2952(96)00094-9.
8
Clathrin-coated vesicles from bovine brain contain uncoupled GABAA receptors.来自牛脑的网格蛋白包被小泡含有未偶联的γ-氨基丁酸A型受体。
Brain Res. 1997 Nov 21;776(1-2):195-203. doi: 10.1016/s0006-8993(97)01037-8.
9
Effects of pentylenetetrazol on GABA-A/benzodiazepine/picrotoxinin receptor complexes in rat brain regions.戊四氮对大鼠脑区γ-氨基丁酸A/苯二氮䓬/印防己毒素受体复合物的影响。
Neurochem Res. 1986 May;11(5):637-46. doi: 10.1007/BF00965333.
10
Loreclezole modulates [35S]t-butylbicyclophosphorothionate and [3H]flunitrazepam binding via a distinct site on the GABAA receptor complex.洛雷唑通过γ-氨基丁酸A受体复合物上的一个独特位点调节[35S]叔丁基双环磷硫代酸盐和[3H]氟硝西泮的结合。
Eur J Pharmacol. 1996 Apr 4;300(1-2):125-30. doi: 10.1016/0014-2999(95)00856-x.
引用本文的文献
1
Multidimensional chemobehavior analysis of flavonoids and neuroactive compounds in zebrafish.斑马鱼中黄酮类和神经活性化合物的多维化学行为分析。
Toxicol Appl Pharmacol. 2018 Apr 1;344:23-34. doi: 10.1016/j.taap.2018.02.019. Epub 2018 Feb 27.
2
Novel analogues of chlormethiazole are neuroprotective in four cellular models of neurodegeneration by a mechanism with variable dependence on GABA(A) receptor potentiation.新型氯甲噻唑类似物通过一种对 GABA(A) 受体增强作用具有可变依赖性的机制，在四种神经退行性变的细胞模型中具有神经保护作用。
Br J Pharmacol. 2014 Jan;171(2):389-402. doi: 10.1111/bph.12454.
3
Activity of chlormethiazole at human recombinant GABA(A) and NMDA receptors.氯美噻唑对人重组γ-氨基丁酸A（GABA(A)）受体和N-甲基-D-天冬氨酸（NMDA）受体的活性。
Br J Pharmacol. 2003 Nov;140(6):1045-50. doi: 10.1038/sj.bjp.0705540. Epub 2003 Oct 6.
4
Pharmacokinetics and sedative effects in healthy subjects and subjects with impaired liver function after continuous infusion of clomethiazole.健康受试者和肝功能受损受试者持续输注氯美噻唑后的药代动力学及镇静作用
Eur J Clin Pharmacol. 2003 Jun;59(2):117-22. doi: 10.1007/s00228-003-0598-y. Epub 2003 May 7.
5
Investigation of the effect of chlormethiazole on cerebral chemistry in neurosurgical patients: a combined study of microdialysis and a neuroprotective agent.氯美噻唑对神经外科患者脑内化学物质的影响研究：微透析与神经保护剂的联合研究
Br J Clin Pharmacol. 2002 Mar;53(3):275-83. doi: 10.1046/j.0306-5251.2001.01552.x.
6
On the regulation of ischaemia-induced glutamate efflux from rat cortex by GABA; in vitro studies with GABA, clomethiazole and pentobarbitone.γ-氨基丁酸对大鼠皮层缺血诱导的谷氨酸外流的调节作用；γ-氨基丁酸、氯美噻唑和戊巴比妥的体外研究
Br J Pharmacol. 2000 Jul;130(5):1124-30. doi: 10.1038/sj.bjp.0703398.
7
Striatal dopamine release in vivo following neurotoxic doses of methamphetamine and effect of the neuroprotective drugs, chlormethiazole and dizocilpine.神经毒性剂量的甲基苯丙胺后体内纹状体多巴胺释放以及神经保护药物氯美噻唑和地佐环平的作用。
Br J Pharmacol. 1993 Mar;108(3):590-6. doi: 10.1111/j.1476-5381.1993.tb12847.x.
8
Chlormethiazole antagonises seizures induced by N-methyl-DL-aspartate without interacting with the NMDA receptor complex.氯美噻唑可拮抗由N-甲基-DL-天冬氨酸诱导的癫痫发作，且不与N-甲基-D-天冬氨酸受体复合物相互作用。
Psychopharmacology (Berl). 1993;112(4):403-6. doi: 10.1007/BF02244886.
9
Chlormethiazole attenuates the derangement of sensory evoked potential (SEP) induced by ICV administration of NMDA.氯美噻唑可减轻由脑室内注射N-甲基-D-天冬氨酸（NMDA）所诱导的感觉诱发电位（SEP）紊乱。
Psychopharmacology (Berl). 1993;111(2):256-8. doi: 10.1007/BF02245534.
10
Effect of chlormethiazole, dizocilpine and pentobarbital on harmaline-induced increase of cerebellar cyclic GMP and tremor.氯美噻唑、地佐环平与戊巴比妥对 harmaline 诱导的小脑环磷酸鸟苷增加及震颤的影响。
Psychopharmacology (Berl). 1993;111(1):96-8. doi: 10.1007/BF02257413.
本文引用的文献
1
Two distinct interactions of barbiturates and chlormethiazole with the GABAA receptor complex in rat cuneate nucleus in vitro.巴比妥类药物和氯美噻唑在体外对大鼠楔束核中GABAA受体复合物的两种不同相互作用。
Br J Pharmacol. 1983 Oct;80(2):387-94. doi: 10.1111/j.1476-5381.1983.tb10045.x.
2
Enhancement of diazepam and gamma-aminobutyric acid binding by (+)etomidate and pentobarbital.依托咪酯（+）和戊巴比妥增强地西泮和γ-氨基丁酸的结合。
J Neurochem. 1983 Aug;41(2):578-85. doi: 10.1111/j.1471-4159.1983.tb04778.x.
3
4
Characteristics of GABAB receptor binding sites on rat whole brain synaptic membranes.大鼠全脑突触膜上GABAB受体结合位点的特征
Br J Pharmacol. 1983 Jan;78(1):191-206. doi: 10.1111/j.1476-5381.1983.tb09380.x.
5
Differential effects of sedative and anticonvulsant barbiturates on specific [3H]GABA binding to membrane preparations from rat brain cortex.镇静性和抗惊厥性巴比妥类药物对大鼠大脑皮层膜制剂中特定[3H]GABA结合的不同影响。
Biochem Pharmacol. 1982 Sep 15;31(18):2891-5. doi: 10.1016/0006-2952(82)90260-x.
6
Regional rat brain benzodiazepine receptor number and gamma-aminobutyric acid concentration following a convulsion.惊厥后大鼠脑局部苯二氮䓬受体数量及γ-氨基丁酸浓度
Br J Pharmacol. 1982 Jun;76(2):291-8. doi: 10.1111/j.1476-5381.1982.tb09219.x.
7
Diazepam and (--)-pentobarbital: fluctuation analysis reveals different mechanisms for potentiation of gamma-aminobutyric acid responses in cultured central neurons.地西泮和（--）-戊巴比妥：波动分析揭示了培养的中枢神经元中γ-氨基丁酸反应增强的不同机制。
Proc Natl Acad Sci U S A. 1981 Nov;78(11):7180-4. doi: 10.1073/pnas.78.11.7180.
8
Interaction of anticonvulsants with the barbiturate-benzodiazepine-GABA receptor complex.抗惊厥药与巴比妥-苯二氮卓-GABA受体复合物的相互作用。
Eur J Pharmacol. 1981 Jun 10;72(1):125-9. doi: 10.1016/0014-2999(81)90309-5.
9
Barbiturate receptor sites are coupled to benzodiazepine receptors.巴比妥酸盐受体位点与苯二氮䓬受体相连。
Proc Natl Acad Sci U S A. 1980 Dec;77(12):7468-72. doi: 10.1073/pnas.77.12.7468.
10
Differential interactions of GABA agonists, depressant and convulsant drugs with [35S]-t-butylbicyclophosphorothionate binding sites in cortex and cerebellum.
Pharmacol Biochem Behav. 1984 Jul;21(1):151-8. doi: 10.1016/0091-3057(84)90145-x.
Zotero 插件