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Protein kinase C epsilon as modulator of anxiety, alcohol consumption and self-administration of drugs of abuse

机译:蛋白激酶C epsilon调节焦虑,饮酒和滥用药物的自我管理

摘要

The present invention is directed to the production of PKC isozyme ε (PKCε)-deficient cells and non-human animals. The present invention is further directed to the identification of PKCε as a target for drugs that reduce anxiety. According to the present invention, PKCε-inhibiting compounds act in synergy with drugs acting at the GABAA receptor. The present invention is also directed to the use of modulators of PKCε to modulate alcohol consumption, self-administration of other drugs of abuse, and the effects of alcohol consumption as well as the use of inhibitors of PKCε, either alone or in conjunction with allosteric agonists of GABAA receptors, to treat conditions, such as addiction, withdrawal syndrome, skeletal muscle spasms, convulsive seizures, and epilepsy, that are amenable to treatment by allosteric agonists of GABAA receptors. Additional aspects of the present invention are diagnostic methods for identifying individuals at risk for becoming alcoholics or abusers of other drugs and kits for performing such diagnostic methods.;The present invention relates to: cells and non-human animals deficient for the PKC isozyme ε (PKCε); the use of PKCε as a target for drugs; the use of inhibitors of PKCε in methods of reducing anxiety and treating conditions associated with insufficient activity of the GABAA receptor; the use of modulators of PKCε in methods of modulating alcohol consumption, modulating self-administration of other drugs of abuse, and altering the effects of alcohol; pharmaceutical compositions comprising inhibitors of PKCε and allosteric agonists of GABAA receptors; and the identification of individuals with enhanced susceptibility to alcoholism or other forms of addiction.
机译:本发明涉及缺乏PKC同工酶ε(PKCε)的细胞和非人类动物的产生。本发明进一步涉及鉴定PKCε作为减少焦虑的药物的靶标。根据本发明,抑制PKCε的化合物与作用于GABA A 受体的药物协同作用。本发明还涉及使用PKCε调节剂来调节酒精消耗,其他滥用药物的自我给药以及酒精消耗的影响以及PKCε抑制剂的使用,无论是单独使用还是与变构结合使用GABA A 受体激动剂,用于治疗成瘾,戒断综合症,骨骼肌痉挛,惊厥性癫痫和癫痫病等适合通过GABA A变构激动剂治疗的疾病子>受体。本发明的其他方面是用于鉴定有可能成为酗酒者或滥用其他药物的风险的个体的诊断方法以及用于执行这种诊断方法的试剂盒。本发明涉及:缺乏PKC同工酶ε的细胞和非人类动物( PKCε); PKCε作为药物靶标的用途; PKCε抑制剂在减轻焦虑和治疗与GABA A 受体活性不足有关的疾病中的用途;在调节酒精消耗,调节其他滥用药物的自我给药以及改变酒精作用的方法中使用PKCε调节剂;药物组合物,其包含PKCε抑制剂和GABA A 受体的变构激动剂;以及识别对酒精中毒或其他形式的成瘾易感性增强的个人。

著录项

  • 公开/公告号US7534859B2

    专利类型

  • 公开/公告日2009-05-19

    原文格式PDF

  • 申请/专利权人 ROBERT O MESSING;CLYDE W HODGE;

    申请/专利号US20060501667

  • 发明设计人 ROBERT O MESSING;CLYDE W HODGE;

    申请日2006-08-08

  • 分类号A61K38;C07K5;C07K14;A01N43/54;A01N43/62;

  • 国家 US

  • 入库时间 2022-08-21 19:30:22

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