A Fundamental study on analysis of ECT imaging using model animals of psycho-neuro disorders

精神神经疾病模型动物ECT成像分析的基础研究

• 批准号: 03670542
• 负责人: MORI Hirofumi
• 金额: $ 0.77万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03670542/
• 关键词: Emission CT; receptor; autoradiography; animal model; schizophrenia; antipsychotic drugs; radiopharmaceuticals; 疾患モデル動物; オ-トラジオグラフィ; 向精神薬

The effects of acute intravenous or chronic subcutaneous haloperidol (HPD) administration on the local cerebral blood flow (LCBF) in 41 regions of the rat brain were studied by means of the quantative autoradiographic N-isopropyl-p- [125-I] iodoamphetamine technique. After acute HPD administrations, the LCBFs decreased in the anterior cingulate cortex, primary motor cortex and primary auditory cortex, and increased the n. habenula. ChronicHPD administration reduced LCBF in the substantia nigra, and increased LCBFs in the n.caudatus-putamen, n.accumbens and n.habenula. No change in LCBF was observed in any cortical region after chronic HPD administratin.An in vivo receptor binding techniques was applied to evaluate the affinities of and clozapine, risperidone, RMI-81582 and haloperidol for dopamine D1, D2, 5- HT2 receptors in the rat brain with [3-H] -SCH23390, [3-H] -YM-09151-2 and [3-H] -Ketanserine as selective ligands. Time course study of receptor occupancy at 25 to 250 min after i … More ntraperitoneal administrations with the drugs showed higher 5-HT2 occupancies in the frontal cortex and lower D2 occupancies in the striatum of clozapine, riperidone and RMI-81582 than those of haloperidol. The 5-HT2/D2 ratios of occupancy for clozapine, riperidone and RMI-81582 were 6-7 times higher than that for haloperidol. Stable occupancies of D1 were observed only with RMI-81582 and clozapine, the former maintaining the higher occupancy. These results are in agreement with the previous findings obtained under in vitro conditions and may account for some part of the properties of atypical antipsychotic drugs.A new ligand, an N-p-lodophenethl diaminodithiol (DADT-IPE), an analog of N- isopropl-p-iodoamphetamine (IMP), was synthesized and subsequently complexed with Tc-99m, using stannous chloride as a reducing agent. Two complexes (a and b) were separated from Tc-99m-DADT-IPE by high performance liquid chromatography. Biodistribution studies suggested that Tc-99m-DADT-IPE (a) has characteristics which are suitable for cerebral perfusion imaging. Less

本文用N-异丙基-p- [125-I]碘苯丙胺放射自显影定量技术，研究了急性静脉或慢性皮下注射氟哌啶醇（HPD）对大鼠41个脑区局部脑血流量（LCBF）的影响。急性HPD给药后，前扣带皮层、初级运动皮层和初级听觉皮层的LCBF降低，n.缰慢性HPD给药降低了黑质的LCBF，增加了尾壳核、缰核和缰核的LCBF。应用受体结合技术，用[3-H] -SCH 23390评价了氯氮平、利培酮、RMI-81582和氟哌啶醇对大鼠脑内多巴胺D1、D2、5-HT 2受体的亲和力，[3-H] -YM-09151-2和[3-H] -酮丝氨酸作为选择性配体。i后25至250 min时受体结合率的时程研究 ...更多信息 氯氮平、利培酮和RMI-81582的额叶皮质5-HT_2占位率高于氟哌啶醇，纹状体D_2占位率低于氟哌啶醇。氯氮平、利培酮和RMI-81582的5-HT_2/D_2占有率比氟哌啶醇高6-7倍。仅RMI-81582和氯氮平观察到D1的稳定占据，前者保持较高的占据。合成了一种新的配体--N-对碘苯乙二胺二硫醇（DADT-IPE），它是N-异丙基-对碘苯丙胺（IMP）的类似物，并以氯化亚锡为还原剂与Tc-99 m形成配合物。用高效液相色谱法从Tc-99 m-DADT-IPE中分离出两种配合物（a和B）。生物分布研究表明，Tc-99 m-DADT-IPE（a）具有适合脑灌注显像的特性。少

项目成果

Shiba K.: "Synthesis of technetiumー99m labeled diaminodithiol for bifunctional chelating agents." Int.J.Radiat.Appl.Instrum.part A.42. 1159-1164 (1991)

Shiba K.：“用于双功能螯合剂的锝－99m 标记二氨基二硫醇的合成。”Int.J.Radiat.Appl.Instrum.part A.42 (1991)。

Sumiyosi T.: "Time Course of Dopamin-1,2 and Serotonin-2 Peceptor Occupancy Rates by Haloperidol and Clozapin in Vivo" Japan. J. Psychiat. Neurol.(1993)

Sumiyosi T.：“体内氟哌啶醇和氯氮平对多巴胺 1,2 和血清素 2 感受器占用率的时间进程”日本。

Sumiyosi T.: "Time Course of Dopamin-1,2 and Serotonin-2 Receptor Occupancy Rates by Haloperidol and Clozapin in Vivo" Japan.J.Psychiat.Neuro1.(1993)

Sumiyosi T.：“体内氟哌啶醇和氯氮平对多巴胺 1,2 和血清素 2 受体占用率的时间进程”Japan.J.Psychiat.Neuro1.(1993)

Shiba K.: "Synthesis of tecnetium-99m labeled diaminodithiol for bifunctionl chelating agents" Int. J. Radiat. Appl. Instrum. part A.42. 1159-1164 (1991)

Shiba K.：“用于双功能螯合剂的 tecnetium-99m 标记的二氨基二硫醇的合成” Int。

Shiba K.: "Shnthesis of technetium-99m labeled diaminoditiol for bifunctional chelating agents" Appl. Radiat. Isot..42(12). 1159-1164 (1991)

Shiba K.：“用于双功能螯合剂的锝-99m 标记二氨基二硫醇的合成”Appl。