DE69833502T2 - Glucocorticoid receptor antagonisten zur behandlung von demenz - Google Patents
Glucocorticoid receptor antagonisten zur behandlung von demenz Download PDFInfo
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- DE69833502T2 DE69833502T2 DE69833502T DE69833502T DE69833502T2 DE 69833502 T2 DE69833502 T2 DE 69833502T2 DE 69833502 T DE69833502 T DE 69833502T DE 69833502 T DE69833502 T DE 69833502T DE 69833502 T2 DE69833502 T2 DE 69833502T2
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- dementia
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- alzheimer
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- glucocorticoid receptor
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| US8570398P | 1998-05-15 | 1998-05-15 | |
| US85703P | 1998-05-15 | ||
| PCT/US1998/020908 WO1999059596A1 (en) | 1998-05-15 | 1998-10-05 | Glucocorticoid receptor antagonists for the treatment of dementia |
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| DE69833502D1 DE69833502D1 (de) | 2006-04-20 |
| DE69833502T2 true DE69833502T2 (de) | 2006-09-28 |
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| DE69833502T Expired - Lifetime DE69833502T2 (de) | 1998-05-15 | 1998-10-05 | Glucocorticoid receptor antagonisten zur behandlung von demenz |
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| US20010046470A1 (en) * | 2000-05-10 | 2001-11-29 | Kieko Morita | Diagnoses and treatment of disorders using an alternative glucose pathway |
| US7163934B2 (en) | 2001-05-04 | 2007-01-16 | Corcept Therapeutics, Inc. | Methods for treating delirium glucocorticoid receptor-specific antagonists |
| IL158744A0 (en) * | 2001-05-04 | 2004-05-12 | Corcept Therapeutics Inc | Methods for treating delirium using glucocorticoid receptor-specific antagonists |
| CN1547473A (zh) | 2001-07-23 | 2004-11-17 | �Ƹ��� | 预防由抗精神病药物引起的体重增加的方法 |
| CN1556708A (zh) * | 2001-08-31 | 2004-12-22 | �Ƹ��� | 抑制成年唐氏综合症患者认知退化的方法 |
| US7326697B2 (en) * | 2002-04-29 | 2008-02-05 | Corcept Therapeutics, Inc. | Methods for increasing the therapeutic response to electroconvulsive therapy |
| US8476254B2 (en) * | 2002-07-02 | 2013-07-02 | Corcept Therapeutics, Inc. | Methods for treating psychosis associated with interferson-α therapy |
| FR2850022B1 (fr) * | 2003-01-22 | 2006-09-08 | Centre Nat Rech Scient | Nouvelle utilisation de la mifepristone et de ses derives comme modulateurs de la voie de signalisation des proteines hedgehog et ses applications |
| US7473903B2 (en) * | 2003-02-12 | 2009-01-06 | General Electric Company | Method and apparatus for deposited hermetic cover for digital X-ray panel |
| ES2819303T3 (es) * | 2005-04-05 | 2021-04-15 | Univ Yale | Agentes moduladores del glutamato en el tratamiento de trastornos mentales |
| WO2008080083A2 (en) * | 2006-12-22 | 2008-07-03 | Washington University | High performance imaging system for diffuse optical tomography and associated method of use |
| US9480425B2 (en) * | 2008-04-17 | 2016-11-01 | Washington University | Task-less optical mapping of dynamic brain function using resting state functional connectivity |
| JP2013511732A (ja) * | 2009-11-24 | 2013-04-04 | コモンウェルス サイエンティフィック アンド インダストリアル リサーチ オーガニゼーション | 神経障害の診断、診断補助および／またはその進行のモニタリングのための方法、キットおよび試薬 |
| PL2576582T3 (pl) * | 2010-05-26 | 2020-06-29 | Corcept Therapeutics, Inc. | Leczenie dystrofii mięśniowej |
| US10500216B2 (en) | 2011-11-18 | 2019-12-10 | Corcept Therapeutics, Inc. | Optimizing mifepristone absorption |
| WO2015187988A1 (en) * | 2014-06-04 | 2015-12-10 | Intellimedix | Composition and methods of treating epilepsy and/or epilepsy-related disorders |
| US9943526B2 (en) | 2015-04-21 | 2018-04-17 | Corcept Therapeutics, Inc. | Optimizing mifepristone levels for cushing's patients |
| US10261310B2 (en) | 2016-06-27 | 2019-04-16 | Amazon Technologies, Inc. | Amorphous silicon layer as optical filter for thin film transistor channel |
| WO2021119432A1 (en) | 2019-12-11 | 2021-06-17 | Corcept Therapeutics Incorporated | Methods of treating antipsychotic-induced weight gain with miricorilant |
| US12194036B2 (en) * | 2022-07-07 | 2025-01-14 | Antecip Bioventures Ii Llc | Combination of dextromethorphan and bupropion for treating depression |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ZA8231B (en) * | 1981-01-09 | 1982-11-24 | Roussel Uclaf | New 11 -substituted steroid derivatives, their preparation, their use as medicaments, the compositions containing them and the new intermediates thus obtained |
| US5348729A (en) | 1988-11-30 | 1994-09-20 | The United States Of America As Represented By The Department Of Health And Human Services | Evaluative means for detecting inflammatory reactivity |
| FR2696934B1 (fr) | 1992-10-20 | 1995-06-02 | Conservatoire Nal Arts Metiers | Dérivés de stéroïdes naturels 3B hydroxyles ayant des propriétés de déclenchement et de stimulation de l'immunité, composition les contenant et procédé pour les obtenir. |
| IL110309A0 (en) * | 1993-07-15 | 1994-10-21 | Univ Kentucky Res Found | A method of protecting against neuron loss |
| IL118974A (en) | 1995-08-17 | 2001-09-13 | Akzo Nobel Nv | History 11 - (Transformed Phenyl) - Astra - 4, 9 - Diane, their preparation and pharmaceutical preparations containing them |
| ATE363908T1 (de) | 1996-04-09 | 2007-06-15 | Univ Edinburgh | Verwendung von 7-alpha-substituierten steroiden zur behandlung von neuropsychiatrischen erkrankungen |
-
1998
- 1998-10-05 DE DE69833502T patent/DE69833502T2/de not_active Expired - Lifetime
- 1998-10-05 IL IL13967298A patent/IL139672A/xx not_active IP Right Cessation
- 1998-10-05 NZ NZ507449A patent/NZ507449A/en not_active IP Right Cessation
- 1998-10-05 CN CN98814043A patent/CN1130200C/zh not_active Expired - Fee Related
- 1998-10-05 EP EP98950912A patent/EP1076562B1/en not_active Expired - Lifetime
- 1998-10-05 WO PCT/US1998/020908 patent/WO1999059596A1/en not_active Ceased
- 1998-10-05 AU AU96833/98A patent/AU756818B2/en not_active Ceased
- 1998-10-05 AT AT98950912T patent/ATE317699T1/de not_active IP Right Cessation
- 1998-10-05 CA CA002328411A patent/CA2328411C/en not_active Expired - Fee Related
- 1998-10-05 JP JP2000549261A patent/JP2003505336A/ja active Pending
- 1998-10-05 KR KR1020007012796A patent/KR20010043630A/ko not_active Withdrawn
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1999
- 1999-02-04 US US09/246,780 patent/US6369046B1/en not_active Expired - Lifetime
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2008
- 2008-11-18 JP JP2008294967A patent/JP2009051864A/ja active Pending
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2009
- 2009-05-22 JP JP2009124741A patent/JP2009185067A/ja active Pending
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| CN1292701A (zh) | 2001-04-25 |
| CA2328411C (en) | 2008-12-16 |
| AU756818B2 (en) | 2003-01-23 |
| US6369046B1 (en) | 2002-04-09 |
| CA2328411A1 (en) | 1999-11-25 |
| EP1076562A1 (en) | 2001-02-21 |
| IL139672A (en) | 2005-11-20 |
| ATE317699T1 (de) | 2006-03-15 |
| WO1999059596A1 (en) | 1999-11-25 |
| JP2009051864A (ja) | 2009-03-12 |
| HK1032535A1 (en) | 2001-07-27 |
| EP1076562B1 (en) | 2006-02-15 |
| JP2003505336A (ja) | 2003-02-12 |
| DE69833502D1 (de) | 2006-04-20 |
| JP2009185067A (ja) | 2009-08-20 |
| AU9683398A (en) | 1999-12-06 |
| IL139672A0 (en) | 2002-02-10 |
| NZ507449A (en) | 2003-08-29 |
| CN1130200C (zh) | 2003-12-10 |
| KR20010043630A (ko) | 2001-05-25 |
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