Methods for predicting psychotropic drugs which elicit weight gain 机翻标题: 暂无翻译,请尝试点击翻译按钮。

公开号/公开日
WO2008036175 A2 2008-03-27 [WO200836175]WO2008036175 A3 2008-10-30 [WO200836175] / 2008-03-272008-10-30
申请号/申请日
2007WO-US19617 / 2007-09-10
发明人
SNYDER SOLOMON H;HUANG ALEX;TEUSCHER CORY;KIM SANGWON;
申请人
JOHNS HOPKINS UNIVERSITY;
主分类号
IPC分类号
A01N-061/00A61K-049/00
摘要
(WO200836175) The atypical antipsychotic drugs (AAPDs) have markedly enhanced the treatment of schizophrenias but their use has been hindered by the major weight gain elicited by some AAPDs.  We found that orexigenic AAPDs potently and selectively activate hypothalamic AMP kinase (AMPK), an action abolished in mice with deletion of histamine Hl receptors.  These findings afford a means of developing better therapeutic agents and provide insight into the hypothalamic regulation of food intake.
机翻摘要
暂无翻译结果,您可以尝试点击头部的翻译按钮。
地址
代理人
代理机构
;
优先权号
2006US-60845505 2006-09-19
主权利要求
(WO200836175) 1. CLAIMS 1. A method of predicting whether an agent which is a psychotropic drug or a candidate psychotropic drug will be orexigenic, comprising the steps of: a. contacting the agent with a histamine Hj receptor (HlR) and determining if the agent binds to the HlR or inhibits histamine binding to the HlR; b. contacting the agent with a hypothalamic adenosine monophosphate kinase (AMPK) and determining if the agent increases phosphorylation or increases activity of the AMPK; c. identifying the agent as likely to be orexigenic when it (a) binds to HlR or inhibits histamine binding to HlR, and (b) increases phosphorylation of hypothalamic AMPK or increases hypothalamic AMPK activity. 2. The method of claim 1 wherein the step of contacting the agent with a hypothalamic AMPK is performed in the presence of leptin or insulin. 3. The method of claim 1 wherein the agent is an anti-depressant drug or candidate antidepressant drug. 4. The method of claim 1 wherein the agent is an anti-psychotic drug or candidate antipsychotic drug. 5. The method of claim 1 wherein the hypothalamic AMPK is in a hypothalamus tissue slice. 6. The method of claim 1 wherein the hypothalamic AMPK is in a hypothalamus cell line. 7. The method of claim 1 wherein the hypothalamic AMPK is in an intact mammal. 8. The method of claim 1 wherein the hypothalamic AMPK is in an intact mouse. 9. The method of claim 1 wherein the HlR is in a crude mammalian brain membrane preparation. 10. The method of claim 1 wherein the HlR is a cloned, human HlR. 11. The method of claim 1 wherein the agent is contacted with a histamine Hi receptor (HlR) and the binding of the agent to the HlR is determined. 12. The method of claim 1 wherein the agent is contacted with a histamine Hi receptor (HlR) and the inhibition of histamine binding to HlR is determined. 13. The method of claim 1 wherein the agent is contacted with a hypothalamic AMPK and an increase in AMPK phosphorylation is determined. 14. The method of claim 1 wherein the agent is contacted with a hypothalamic AMPK and an increase in AMPK activity is determined. 15. The method of claim 1 wherein the agent is contacted with a histamine Hi receptor (HlR) and the binding of the agent to the HlR is determined and the agent is contacted with a hypothalamic AMPK and an increase in AMPK phosphorylation is determined. 16. The method of claim 1 wherein the agent is contacted with a histamine Hi receptor (HlR) and the binding of the agent to the HlR is determined and the agent is contacted with a hypothalamic AMPK and an increase in AMPK activity is determined. 17. The method of claim 1 wherein the agent is contacted with a histamine Hi receptor (HlR) and the inhibition of histamine binding to HlR is determined and the agent is contacted with a hypothalamic AMPK and an increase in AMPK phosphorylation is determined. 18. The method of claim 1 wherein the agent is contacted with a histamine Hi receptor (HlR) and the inhibition of histamine binding to HlR is determined and the agent is contacted with a hypothalamic AMPK and an increase in AMPK activity is determined. 19. A method of predicting whether an agent which is a psychotropic drug or a candidate psychotropic drug will be orexigenic, comprising the steps of: a. contacting the agent with an isogenic pair of hypothalamic cells comprising a first and a second cell, wherein the first cell is deficient in histamine type I receptor (HIR) and the second cell is wild-type for histamine type I receptor; b. determining if the agent increases phosphorylation or increases activity of hypothalamic AMPK in the first and second cells; c. identifying the agent as likely to be orexigenic when it increases phosphorylation of hypothalamic AMPK or increases hypothalamic AMPK activity in the second cell to a significantly greater extent than in the first cell. 20. The method of claim 19 wherein phosphorylation of hypothalamic AMPK is determined. 21. The method of claim 19 wherein activity of hypothalamic AMPK is determined. 22. The method of claim 19 wherein the first and second cells are in mice. 23. The method of claim 19 wherein the first and second cells are in vitro.
法律状态
(WO200836175) LEGAL DETAILS FOR WO2008036175  Actual or expected expiration date=2010-03-19    Legal state=DEAD    Status=LAPSED     Event publication date=2007-09-10  Event code=WO/APP  Event indicator=Pos  Event type=Examination events  Application details  Application country=WO WOUS2007019617  Application date=2007-09-10  Standardized application number=2007WO-US19617     Event publication date=2008-03-27  Event code=WO/A2  Event type=Examination events  International application published without international search report  Publication country=WO  Publication number=WO2008036175  Publication stage Code=A2  Publication date=2008-03-27  Standardized publication number=WO200836175     Event publication date=2008-10-30  Event code=WO/A3  Event indicator=Pos  Event type=Examination events  Later publication of ISR with revised front page  Publication country=WO  Publication number=WO2008036175  Publication stage Code=A3  Publication date=2008-10-30  Standardized publication number=WO200836175     Event publication date=2010-03-19  Event code=WO/EETL  Event type=Event indicating Not In Force  PCT Application validity period expired. LEGAL DETAILS FOR DESIGNATED STATE DE  Actual or expected expiration date=2009-03-20    Legal state=DEAD    Status=LAPSED   Corresponding cc:  Designated or member state=DE     Event publication date=2009-03-20  Event code=WO/NENP  Event type=Event indicating Not In Force  Non-entry into the national phase in: Corresponding cc:  Designated or member state=DE  LEGAL DETAILS FOR DESIGNATED STATE US2009304596  Actual or expected expiration date=2027-09-10    Legal state=ALIVE    Status=GRANTED   Corresponding cc:  Designated or member state=US Corresponding appl: US12441986  Application date in the designated or member state=2007-09-10   Application number in the designated or member state=2007US-12441986 Corresponding cc:  Designated or member state=US Corresponding pat: US2009304596  Publication stage code in the designated or member state=A1  Publication date in the designated or member state=2009-12-10   Publication number in the designated or member state=US20090304596    Event publication date=2009-07-22  Event code=WO/WWE  Event indicator=Pos  Event type=Entry into national phase  Wipo information: entry into national phase Corresponding cc:  Designated or member state=US     Event publication date=2017-11-30  Event code=US/STCHG  Patent Status changed by the national office Corresponding cc:  Designated or member state=US
专利类型码
A2A3
国别省市代码
若您需要申请原文,请登录。

最新评论

暂无评论。

登录后可以发表评论

意见反馈
返回顶部