公开(公告)号：US06258556B1

公开(公告)日：2001-07-10

申请号：US08188275

申请日：1994-01-28

申请人： George Uhl ,  Peter Johnson ,  Antonio M. Persico ,  Jia Bei Wang

发明人： George Uhl ,  Peter Johnson ,  Antonio M. Persico ,  Jia Bei Wang

IPC分类号： C12P2106

CPC分类号： C07K14/70571 ,  A61K38/00 ,  C07K14/705

摘要： A human &mgr; opiate receptor cDNA has been identified from a cerebral cortical CDNA library using sequences from the rat &mgr; opiate receptor CDNA. The human &mgr; opiate receptor (h&mgr;OR1) shares 95% amino acid identity with the rat sequence. The expressed &mgr;OR1 recognizes tested opiate drugs and opioid peptides in a sodium- and GTP-sensitive fashion with affinities virtually identical to those displayed by the rat &mgr; opiate receptor. Effects on cyclic AMP are similar to those noted for the rat &mgr; opiate receptor. Overlapping genomic clones spanning 50 kilobasepairs and hybridizing with the h&mgr;OR1 cDNA contains exon sequences encoding the entire open reading frame of the human A opiate receptor are described. Analysis of hybridization to DNA prepared from human rodent hybrid cell lines and chromosomal in situ hybridization studies indicate localization to 6q24-25. An MspI polymorphism, producing a 3.7 kb band, is being used to assess this gene's involvement in neuropsychiatric disorders involving opiatergic systems.

摘要翻译： 已经使用来自大鼠mu鸦片受体CDNA的序列从大脑皮质CDNA文库中鉴定了人类鸦片剂受体cDNA。 人类鸦片剂受体（hmuOR1）与大鼠序列具有95％的氨基酸同一性。 表达的muOR1以钠和GTP敏感的方式识别测试的阿片样物质和阿片样物质肽，其亲和力与大鼠mu鸦片受体显示的亲和力几乎相同。 对环AMP的作用与大鼠mu鸦片受体相似。 描述跨越50千碱基并与hmuOR1 cDNA杂交的重叠基因组克隆包含编码人A阿片受体的整个开放阅读框的外显子序列。 从人类啮齿动物杂交细胞系制备的DNA杂交分析和染色体原位杂交研究表明定位于6q24-25。 正在使用产生3.7kb带的MspI多态性来评估该基因参与涉及opiatgic系统的神经精神障碍。

公开(公告)号：US10016413B2

公开(公告)日：2018-07-10

申请号：US14025434

申请日：2013-09-12

申请人： Jia Bei Wang ,  Sarah Sushchyk

发明人： Jia Bei Wang ,  Sarah Sushchyk

IPC分类号： A01N43/40 ,  A61K31/473 ,  A61K31/485 ,  A61K45/06 ,  A61K31/4745

CPC分类号： A61K31/485 ,  A61K31/473 ,  A61K31/4745 ,  A61K45/06 ,  A61K2300/00

摘要： The present invention is directed to a method of treating or preventing an addictive behavior in a subject, said method comprising administering to said subject an effective amount of a dopamine antagonist and a opiate receptor antagonist or a composition comprising same. Further provided are pharmaceutical compositions comprising, as active substances, at least one dopamine antagonist and at least one opiate receptor antagonist.

公开(公告)号：US20140073664A1

公开(公告)日：2014-03-13

申请号：US14025434

申请日：2013-09-12

申请人： Jia Bei Wang ,  Sarah Sushchyk

发明人： Jia Bei Wang ,  Sarah Sushchyk

IPC分类号： A61K31/485 ,  A61K45/06 ,  A61K31/473

CPC分类号： A61K31/485 ,  A61K31/473 ,  A61K31/4745 ,  A61K45/06 ,  A61K2300/00

摘要： The present invention is directed to a method of treating or preventing an addictive behavior in a subject, said method comprising administering to said subject an effective amount of a dopamine antagonist and a opiate receptor antagonist or a composition comprising same. Further provided are pharmaceutical compositions comprising, as active substances, at least one dopamine antagonist and at least one opiate receptor antagonist.

摘要翻译： 本发明涉及治疗或预防受试者成瘾行为的方法，所述方法包括向所述受试者施用有效量的多巴胺拮抗剂和阿片剂受体拮抗剂或包含其的组合物。 还提供了药物组合物，其包含作为活性物质的至少一种多巴胺拮抗剂和至少一种阿片剂受体拮抗剂。

公开(公告)号：US20100235931A1

公开(公告)日：2010-09-16

申请号：US12223150

申请日：2007-02-09

申请人： Jia Bei Wang

发明人： Jia Bei Wang

IPC分类号： A01K67/033 ,  C12Q1/68 ,  A61K31/7088 ,  A61K31/711 ,  A61K38/02 ,  A61K39/395 ,  A61P25/18

CPC分类号： A61K38/16 ,  A01K67/0276 ,  A01K2217/075 ,  A01K2227/105 ,  A01K2267/0356 ,  A61K31/485

摘要： Wildtype and mice lacking the gene encoding PKCI/HINT 1 (PKC−/−) were used to assess the involvement of PKCI/HINT1 in regulating basal locomotor activity and the behavioral activating effects of the psychostimulant, amphetamine. PKCl−/− mice displayed low level of spontaneous locomotion relative to WT littermates. Acute administration of amphetamine significantly increased locomotor activity in WT mice; an effect that was enhanced in PKCl−/− mice. Microdialysis studies revealed no alteration in basal DA dynamics in the striatum and nucleus accumbens of KO mice. Similarly, the ability of acute amphetamine to increase DA levels in these brain regions was unaltered. However, a dopamine receptor agonist, apomorphine (10 mg/kg), was able to induce a significantly higher locomotor activity in PKCI−/− mice as compared with WT, suggesting there may be a dopaminergic functional change at the postsynaptic site. Our results also revealed that PKCI KO mice showed a less depression and anxiety trait than their litter mate controls (WT), which indicate that PKCI could also play a role in regulating the emotion states of brain. Together, these results indicated that PKCI/HINT1 may have a suppressive role in normal DA neurotransmission, and may also play an important role for the action of psychostimulants in schizophrenia.

摘要翻译： 使用缺乏编码PKCI / HINT1（PKC - / - ）基因的野生型和小鼠来评估PKCI / HINT1参与调节基础运动活动和精神兴奋剂苯丙胺胺的行为活化作用。 PKCl - / - 小鼠相对于WT同窝出生显示出低水平的自发运动。 安非他明的急性给药显着增加WT小鼠的运动活性; 在PKC1 - / - 小鼠中增强的作用。 微透析研究显示KO小鼠的纹状体和伏隔核中的基础DA动力学没有改变。 类似地，急性苯丙胺胺在这些脑区域中增加DA水平的能力是未改变的。 然而，与WT相比，多巴胺受体激动剂阿扑吗啡（10mg / kg）能够在PKCI - / - 小鼠中诱导显着更高的运动活性，表明突触后部位可能存在多巴胺能功能变化。 我们的研究结果还表明，PKCI KO小鼠的凋亡抑制和焦虑特征比其凋零物质控制（WT）低，这表明PKCI也可以在调节脑的情绪状态方面发挥作用。 这些结果一起表明，PKCI / HINT1可能在正常DA神经传递中具有抑制作用，并且也可能对精神分裂症患者精神分裂症的作用起重要作用。