[1]鲍伟奇,邱春,管一晖.γ-氨基丁酸A型-苯二氮革受体显像剂在神经系统疾病中的应用[J].国际放射医学核医学杂志,2012,36(1):1-8.[doi:10.3760/cma.j.issn.1673-4114.2012.01.001]
 BAO Wei-qi,QIU Chun,GUAN Yi-hui.Application of gamma-aminobutyric acid type A-benzodiazepine receptor imaging for study of neuropsychiatric disorders[J].International Journal of Radiation Medicine and Nuclear Medicine,2012,36(1):1-8.[doi:10.3760/cma.j.issn.1673-4114.2012.01.001]
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γ-氨基丁酸A型-苯二氮革受体显像剂在神经系统疾病中的应用(/HTML)
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《国际放射医学核医学杂志》[ISSN:1673-4114/CN:12-1381/R]

卷:
36
期数:
2012年第1期
页码:
1-8
栏目:
实验核医学
出版日期:
2012-01-25

文章信息/Info

Title:
Application of gamma-aminobutyric acid type A-benzodiazepine receptor imaging for study of neuropsychiatric disorders
作者:
鲍伟奇 邱春 管一晖
200235 上海, 上海复旦大学附属华山医院PET中心
Author(s):
BAO Wei-qi QIU Chun GUAN Yi-hui
PET Center, Huashan Hospital, Fudan University, Shanghai 200235, China
关键词:
神经系统疾病受体GABA-A正电子发射断层显像术
Keywords:
Nervous system diseasesReceptors GABA-APositron-emission tomography
DOI:
10.3760/cma.j.issn.1673-4114.2012.01.001
摘要:
γ-氨基丁酸A型-苯二氮革(GABAA-BZ)受体广泛分布于中枢神经系统,是嵌于神经细胞膜上的异质性多肽五聚体,不同的亚单位组合发挥不同的神经抑制性药理作用,如镇静催眠、抗惊厥、抗焦虑等。PET可用于活体内受体结合的研究。GABAA-BZ受体PET显像剂分为拮抗剂、激动剂、反向激动剂3类,其中以拮抗剂显像剂11C-氟马西尼最为成熟,在癫癎、焦虑症、抑郁症、植物状态、成瘾等神经精神疾病中广泛应用。
Abstract:
Gamma-aminobutyric acid type A-benzodiazepine receptors are heterogeneous polypeptide pentamers widely spread in the central nervous system on the neuron membrane.Different subunit combinations educe various neuro-inhibitory pharmacological effects such as sedative,hypnosis,anticonvulsion and anxiolysis.PET can be utilized to study the binding of the receptors in vivo.PET radioligands of gammaaminobutyric acid type A-benzodiazepine receptors can be classified into 3 types:antagonists,agonists and reverse agonists,of which antagonist radiotracer 11C-flumazenil is the most commonly applied in epilepsy,anxiety disorders,depression,vegetative state,addiction and other neuro-psychiatric disorders.

参考文献/References:

[1] 朱大年.神经系统功能活动的基本原理//姚泰.生理学.北京:人民卫生出版社,2005:410-411.
[2] 胡刚.镇静催眠药//杨世杰.药理学.北京:人民卫生出版社.2005:196-197.
[3] Olsen RW, Sieghart W. GABAA receptors:Subtypes provide diversity of function and pharmacology. Neuropharmacology, 2009, 56(1):141-148.
[4] Lüddens H, Seeburg PH, Korpi ER. Impact of beta and gamma variants on ligand-binding properties of gamma-aminobutyric acid type A receptors. Mol Pharmacol, 1994, 45(5):S10-814.
[5] Wingrove PB, Wafford KA, Bain C, et al. The modulatory action of loreclezole at the gamma-aminobutyric acid type A receptor is determined by a single amino acid in the beta 2 and beta 3 subunit. Proc Natl Acad Sci USA, 1994, 91(10):4569-4573.
[6] Korpi ER, Kuner T, Seeburg PH, et al. Selective antagonist for the cerebellar granule cell-specific gamma-aminobutyric acid type A receptor. Mol Pharmacol, 1995, 47(2):283-289.
[7] Pirker S, Schwarzer C, Wiesehhaler A, et al. GABA receptors:immunocytochemical distribution of 13 subunits in the adult rat brain. Neuroscience, 2000, 101(4):815-850.
[8] Uusi-Oukari M, Korpi ER. Regulation of GABAA receptor subunit expression by pharmacological agents. Pharmacol Rev, 2010, 62(1):97-135.
[9] Yee BK, Keist R, yon Boehmer L, et al. A schizophrenia-related sensorimotor deficit links α3-containing GABAA receptors to a dopamine hyperfunction. Proc Natl Acad Sci USA, 2005, 102(47):17154-17159.
[10] Smith SS, Gong QH, Hsu FC, et al. GABA receptor α4 subunit suppression prevents withdrawal properties of an endogenous steroid. Nature, 1998, 392(6679):926-930.
[11] Holt RA, Bateson AN, Martin IL. Chronic treatment with diazepam or abecanlil differently affects the expression of GABAA receptor subunit mRNAs in the rat cortex. Neuropharmacology, 1996, 35(9-10):1457-1463.
[12] Collinson N, Kuenzi FM, Jarolimek W, et al. Enhanced learning and memory and altered GABAergic synaptic transmission in mice lacking the alpha 5 subunit of the GABA receptor. J Neurosci, 2002, 22(13):5572-5580.
[13] Korpi ER, Kleingoor C, Kettenmann H, et al. Benzodiazepine-induced motor impairment linked to point mutation in cerebellar GABAA receptor. Nature. 1993, 361(6410):356-359.
[14] Jurd R, Arras M, Lambert S, et al. General anesthetic actions in vivo strongly attenuated by a point mutation in the GABA receptor β3 subunit. FASEB J:2003, 17(2):250-252.
[15] Reynolds DS, Rosahl TW, Cirone J, et al. Sedation and anesthesia mediated by distinct GABAA receptor isoforms. J Neurosci, 2003,23(24):8608-8617.
[16] Zeller A, Arras M, Lazaris A, et al. Distinct molecular targets for the central respiratory and cardiac actions of the general anesthetics etomidate and propofol. FASEB J, 2005, 19(12):1677-1679.
[17] Cirone J, Rosahl TW, Reynolds DS, et al.γ-aminobutyric acid type A receptor β2 subunit mediates the hypothermic effect of etomidate in mice. Anesthesiology, 2004, 100(6):1438-1445.
[18] Homanics GE, DeLorey TM, Firestone LL, et al. Mice devoid of γ-aminobutyrate type A receptor β3 subunit have epilepsy, cleft palate, and hypersensitive behavior. Proc Natl Aead Sci USA, 1997, 94(8):4143-4148.
[19] Günther U, Benson J, Benke D, et al. Benzodiazepine-insensitive mice generated by targeted disruption of the γ2 subunit gene of γ-aminobutyric acid type A receptors. Proc Natl Aead Sci USA, 1995, 92(17):7749-7753.
[20] Mihalek RM, Bowers B J, Wehner JM, et al. GABAA receptor delta subunit knockout mice have multiple defects in behavioral responses to ethanol. Alcohol Clin Exp Res, 2001, 25(12):1708-1718.
[21] Maziere M, Hantraye P, Prenant C, et al. Synthesis of ethyl 8-fluo-ro-5,6-dihydro-5-[11C] methyl-6-oxo-4H-imidazo[1,5-a] [1,4] benzodiazepine-3-carboxylate (RO 15.1788-11C):A specific radioligand for the in vivo study of central benzodiazepine receptors by positron emission tomography. Int J Appl Radiat Isot, 1984, 35(10):973-976.
[22] Suzuki K, Inoue O, Hashimoto K, et al. Computer-con-trolled large scale production of high specific activity[11C] RO 15-1788 for PET studies of benzodiazepine receptors. Int J Appl Radiat Isot, 1985, 36(12):971-976.
[23] Debruyne D, Abadie P, Barre L, et al. Plasma pharmacokinetics and metabolism of the benzodiazepine antagonist[11C] Ro 15-1788(flumazenil) in baboon and human during positron emission tomography studies. Eur J Drug Metab Pharmacokinet, 1991, 16(2):141-152.
[24] Chugani D, Muzik O, Juhász C, et al. Postnatal maturation of human GABAA receptors measured with positron emission tomography. Ann Neurol, 2001, 49(5):618-626.
[25] Salmi E, Kaisti K, Metsahonkala L, et al. Sevoflurane and propofol increase 11C-flumazenil binding to gamma-aminobutyric acidA receptors in humans. Anesth Analg, 2004, 99(5):1420-1426.
[26] Prevett MC, Lammertsma AA, Brooks D J, et al. Benzodiazepine-GABAA receptors in idiopathic generalized epilepsy measured[11C] flumazenil and positron emission tomography. Epilepsia, 1995, 36(2):113-121.
[27] Koepp M J, Richardson MP, Brooks DJ, et al. Central benzodiazepine/γ-aminobutyric acid A receptors in idiopathic generalized epilepsy:an[11C] flumazenil positron emission tomography study. Epilepsia, 1997, 38(10):1089-1097.
[28] Odano I, Halldin C, Karlsson P, et al.[18F] flumazenil binding to central benzodiazepine receptor studies by PET-Quantitative analysis and comparisons with[11C] flumazenil-. Neurolmage, 2009, 45(3):891-902.
[29] Dedearwaerdere S, Gregoire MC, Vivash L, et al. In-vivo imaging characteristics of two fluorinated flumazenil radiotracers in the rat. Eur J Nucl Med Mol Imaging, 2009, 36(6):958-965.
[30] Gründer G, Siessmeier T, Lange-Asschenfeldt C, et al.[18F] Fluo-roethylflumazenil:a novel tracer for PET imaging of human benzo-diazepine receptors. Eur J Nucl Med, 2001, 28(10):1463-1470.
[31] Comar D, Maziere M, Cepeda C, et al. The kinetics and displace-ment of[11C] flunitrazepam in the brain of the living baboon. Eur J Pharmacol, 1981, 75(1):21-26.
[32] Comar D, Maziere M, Godot JM, et al. Visualisation of 11C-fluni-trazepam displacement in the brain of the live baboon. Nature, 1979, 280(5720):329-331.
[33] Ishiwata K, Yanai K, Ido T, et al. Synthesis and biodistribution of[11C] fludiazepam for imaging benzodiazepine receptors. Int J Rad Appl Instrum B, 1988, 15(4):365-371.
[34] Bottlaender M, Brouillet E, Varastet al, et al. In vivo high intrinsic efficacy of triazolam:a positron emission tomography study in non-human primates. J Neurochem, 1994, 62(3):1102-1111.
[35] Dobbs FR, Banks W, Fleishaker JC, et al. Studies with[11C] alprazolam:an agonist for the benzodiazepine receptor. Nucl Med Biol, 1995, 22(4):459-466.
[36] Frost JJ, Wagner HN Jr, Dannals RF, et al. Imaging benzodiazepine receptors in man with[11C] suriclone by positron emission tomography. Eur J Pharmacol, 1986, 122(3):381-383.
[37] la Fougère C, Rominger A, Förster S, et al. PET and SPECT in epilepsy:A critical review. Epilepsy Behav, 2009, 15(1):50-55.
[38] Savie I, Persson A, Roland P, et al. In-vivo demonstration of reduced benzodiazepine receptor binding in human epileptic foci. Lancet, 1988, 2(8616):863-866.
[39] Muzik O, da Silva EA, Juhasz C, et al. Intracranial EEG versus flumazenil and glucose PET in children with extratemporal lobe epilepsy. Neurology, 2000, 54(1):171-179.
[40] Koepp MJ, Labbé C, Richardson MP, et al. Regional hippocampal[11C] flumazenil PET in temporal lobe epilepsy with unilateral and bilateral hippocampal sclerosis. Brain, 1997, 120(10):1865-1876.
[41] Hammers A, Koepp MJ, Richardson MP, et al. Central benzodi-azepine receptors in malformations of cortical development:A quantitative study. Brain, 2001, 124(8):1555-1565.
[42] Koepp MJ, Hammers A, Labbe C, et al. 11C-flumazenil PET in patients with refractory temporal lobe epilepsy and normal MRI. Neurology, 2000, 54(2):332-339.
[43] Savie I, Widen L, Thorell JO, et al. Cortical benzodiazepine receptor binding in patients with generalized and partial epilepsy. Epilepsia, 1990, 31(6):724-730.
[44] Savic I, Pauli S, Thorell JO, et al. In vivo demonstration of altered benzodiazepine receptor density in patients with generalised epilepsy. J Neurol Neurosurg Psychiatry, 1994, 57(7):797-804.
[45] Abadie P, Boulenger JP, Benali K, et al. Relationships between trait and state anxiety and the central benzodiazepine receptor:a PET study. Eur J Neurosci, 1999, 11(4):1470-1478.
[46] Malizia AL, Cunningham VJ, Bell CJ, et al. Decreased brain GABAA-benzodiazepine receptor binding in panic disorder:preliminary results from a quantitative PET study. Arch Gen Psychiatry, 1998, 55(8):715-720.
[47] Hasler G, Nugent AC, Carlson PJ, et al. Altered cerebral γ-aminobutyric acid type A-benzodiazepine receptor binding in panic disorder determined by[11C]flumazenil positron emission tomography. Arch Gen Psychiatry, 2008, 65(10):l 166-1175.
[48] Klumpers UM, Veltman DJ, Drent ML, et al. Reduced parahip-pocampal and lateral temporal GABAA-[11C] flumazenil binding in major depression:preliminary results. Eur J Nucl Med Mol Imaging, 2010, 37(3):565-574.
[49] Rudolf J, Sobesky J, Ghaemi M, et al. The correlation between cerebral glucose metabolism and benzodiazepine receptor density in the acute vegetative state. Eur J Neurol, 2002, 9(6):671-677.
[50] Lingford-Hughes AR, Wilson SJ, Cunningham V J, et al. GABA-benzodiazepine receptor function in alcohol dependence:a com-bined 11C-flumazenil PET and pharmacodynamic study. Psychopharmacology(Berl), 2005, 180(4):595-606.
[51] Veselis RA, Reinsel RA, Beattie BJ, et al. Midazolam changes cerebral blood flow in discrete brain regions:an H215O positron emission tomography study. Anesthesiology, 1997, 87(5):1106-1117.
[52] Holopainen IE, Metsähonkala E, Kokkonen H, et al. Decreased binding of[11C]flumazenil in Angelman syndrome patients with GABAA receptor β3 subunit deletions. Ann NeuroI, 200l, 49(1):110-113.
[53] Asahina N, Shiga T, Egawa K, et al.[11C]flumazenil positron emission tomography analyses of brain gamma-aminobutyric acid type A receptors in Angelman syndrome. J Pediatr, 2008, 152(4):546-549.
[54] Lucignani G, Panzacchi A, Bosio L, et al. GABAA receptor abnor-malities in Prader Willi syndrome assessed with positron emission tomography and[11C]flumazenil. Neuroimage, 2004, 22(1):22-28.

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备注/Memo

备注/Memo:
收稿日期:2011-11-08。
通讯作者:管一晖,Email:guanyihui@hotmail.com
更新日期/Last Update: 1900-01-01