HUP9904401A2 - Controlled release dosage form of [r-(z)]-alpha-(methoxyimino)-alpha-(1-azabicyclo[2.2.2]oct-3-yl)acetonitrile monohydrochloride - Google Patents
Controlled release dosage form of [r-(z)]-alpha-(methoxyimino)-alpha-(1-azabicyclo[2.2.2]oct-3-yl)acetonitrile monohydrochlorideInfo
- Publication number
- HUP9904401A2 HUP9904401A2 HU9904401A HUP9904401A HUP9904401A2 HU P9904401 A2 HUP9904401 A2 HU P9904401A2 HU 9904401 A HU9904401 A HU 9904401A HU P9904401 A HUP9904401 A HU P9904401A HU P9904401 A2 HUP9904401 A2 HU P9904401A2
- Authority
- HU
- Hungary
- Prior art keywords
- alpha
- dosage form
- methoxyimino
- oct
- disease
- Prior art date
Links
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 title abstract 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 title abstract 2
- 238000013270 controlled release Methods 0.000 title abstract 2
- 239000002552 dosage form Substances 0.000 title abstract 2
- 208000024827 Alzheimer disease Diseases 0.000 abstract 3
- 150000001875 compounds Chemical class 0.000 abstract 2
- 101710137189 Amyloid-beta A4 protein Proteins 0.000 abstract 1
- 101710151993 Amyloid-beta precursor protein Proteins 0.000 abstract 1
- 102100022704 Amyloid-beta precursor protein Human genes 0.000 abstract 1
- 206010012289 Dementia Diseases 0.000 abstract 1
- 241000124008 Mammalia Species 0.000 abstract 1
- DZHSAHHDTRWUTF-SIQRNXPUSA-N amyloid-beta polypeptide 42 Chemical compound C([C@@H](C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@H](C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)NCC(=O)N[C@@H](C(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](C)C(O)=O)[C@@H](C)CC)C(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C(C)C)C1=CC=CC=C1 DZHSAHHDTRWUTF-SIQRNXPUSA-N 0.000 abstract 1
- 230000015572 biosynthetic process Effects 0.000 abstract 1
- 239000012458 free base Substances 0.000 abstract 1
- 239000006186 oral dosage form Substances 0.000 abstract 1
- 230000037361 pathway Effects 0.000 abstract 1
- 230000002265 prevention Effects 0.000 abstract 1
- 108090000623 proteins and genes Proteins 0.000 abstract 1
- 150000003839 salts Chemical class 0.000 abstract 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/439—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom the ring forming part of a bridged ring system, e.g. quinuclidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1617—Organic compounds, e.g. phospholipids, fats
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2054—Cellulose; Cellulose derivatives, e.g. hydroxypropyl methylcellulose
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/205—Polysaccharides, e.g. alginate, gums; Cyclodextrin
- A61K9/2059—Starch, including chemically or physically modified derivatives; Amylose; Amylopectin; Dextrin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2072—Pills, tablets, discs, rods characterised by shape, structure or size; Tablets with holes, special break lines or identification marks; Partially coated tablets; Disintegrating flat shaped forms
- A61K9/2086—Layered tablets, e.g. bilayer tablets; Tablets of the type inert core-active coat
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/5073—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings
- A61K9/5078—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals having two or more different coatings optionally including drug-containing subcoatings with drug-free core
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Biomedical Technology (AREA)
- Hospice & Palliative Care (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Psychiatry (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biophysics (AREA)
- Molecular Biology (AREA)
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Steroid Compounds (AREA)
Abstract
A találmány[R- Z)]-a-(metőxi-iminő)-a-(1-aza-biciklő-[2.2.2]őkt-3-il)-acetőnitril-mőnőhidrőklőridőt (X. vegyületet), a vegyület szabadbázisát vagy bármely más gyógyászatilag elfőgadható sóját tartalmazó,szabályőzőtt kibőcsátású őrális dózisfőrmára vőnatkőzik. A találmánytárgyát képezi tővábbá a találmány szerinti dózisfőrma alkalmazásaemlősökben dementia, ezen belül Alzheimer-kór kezelésére és/vagymegelőzésére, valamint Alzheimer-kórban szenvedő vagy az Alzheimer-kórkifejlődésével fenyegetett betegekben az amilőid prekűrzőr prőteinnem-amilőidőgén útőn történő képződésének főkőzására szőlgálógyógyszerkészítmény előállítására. ŕThe invention provides [R-Z]-α-(methoxyimino)-α-(1-aza-bicyclo-[2.2.2]oct-3-yl)-acetonitrile monohydrochloride (compound X), the free base of the compound or any other controlled-release oral dosage form containing medicinally soluble salt. Further, the subject of the invention is the use of the dosage form according to the invention in mammals for the treatment and/or prevention of dementia, including Alzheimer's disease, and for the production of a medicinal preparation that inhibits the formation of the amyloid precursor protein via the non-amyloid gene pathway in patients suffering from Alzheimer's disease or at risk of developing Alzheimer's disease. ŕ
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9619074.9A GB9619074D0 (en) | 1996-09-12 | 1996-09-12 | Composition |
| PCT/GB1997/002418 WO1998010762A2 (en) | 1996-09-12 | 1997-09-08 | Controlled release dosage form of r-(z)-alpha-methoxyimino-alpha-(1-azabicyclo2.2oct-c-yl)acetonitrile monohydrochloride |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| HUP9904401A2 true HUP9904401A2 (en) | 2000-06-28 |
| HUP9904401A3 HUP9904401A3 (en) | 2001-03-28 |
Family
ID=10799833
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| HU9904401A HUP9904401A3 (en) | 1996-09-12 | 1997-09-08 | Controlled release dosage form of [r-(z)]-alpha-(methoxyimino)-alpha-(1-azabicyclo[2.2.2]oct-3-yl)acetonitrile monohydrochloride |
Country Status (22)
| Country | Link |
|---|---|
| EP (1) | EP0929301A2 (en) |
| JP (1) | JP2001500150A (en) |
| KR (1) | KR20000036039A (en) |
| CN (2) | CN1235544A (en) |
| AR (1) | AR008176A1 (en) |
| AU (1) | AU724086B2 (en) |
| BR (1) | BR9711734A (en) |
| CA (1) | CA2265661A1 (en) |
| CO (1) | CO5031291A1 (en) |
| CZ (1) | CZ83299A3 (en) |
| GB (1) | GB9619074D0 (en) |
| HU (1) | HUP9904401A3 (en) |
| ID (1) | ID19589A (en) |
| IL (1) | IL128781A0 (en) |
| MA (1) | MA24359A1 (en) |
| NO (1) | NO991194L (en) |
| NZ (1) | NZ334268A (en) |
| PE (1) | PE2499A1 (en) |
| PL (1) | PL332074A1 (en) |
| TR (1) | TR199900505T2 (en) |
| WO (1) | WO1998010762A2 (en) |
| ZA (1) | ZA978133B (en) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FR2775597B1 (en) * | 1998-03-04 | 2001-04-20 | Gattefosse Ets Sa | ORAL PELLET ADAPTED TO IMPROVE THE BIOAVAILABILITY OF THE ACTIVE SUBSTANCE, METHOD OF MANUFACTURE |
| WO1999045924A1 (en) | 1998-03-11 | 1999-09-16 | Smithkline Beecham Plc | Composition |
| DE19918325A1 (en) * | 1999-04-22 | 2000-10-26 | Euro Celtique Sa | Extruded drug dosage form, e.g. granulate for tableting, comprising an active agent in a polysaccharide-containing matrix, giving a release profile which is controllable by extrusion conditions and/or the inclusion of additives |
| FR2796840B1 (en) * | 1999-07-26 | 2003-06-20 | Ethypharm Lab Prod Ethiques | LOW-DOSE TABLETS AND METHOD OF PREPARATION |
| US6733781B2 (en) * | 2000-12-06 | 2004-05-11 | Wyeth | Fast dissolving tablet |
| MY142204A (en) | 2002-07-25 | 2010-10-29 | Pharmacia Corp | Pramipexole once-daily dosage form |
| CA2520813C (en) * | 2003-04-25 | 2009-10-27 | Mitsubishi Pharma Corporation | Sustained release formulations of alkylene dioxybenzene derivatives useful as 5-ht1a agonists |
| DE602004002405T3 (en) * | 2003-05-14 | 2013-06-20 | Aptalis Pharma Limited | CONTROLLED MEDICATION RELEASE COMPOSITION WITH IN VIVO MECHANICAL RESISTANCE |
| US20050142191A1 (en) * | 2003-06-23 | 2005-06-30 | Neurochem (International) Limited | Pharmaceutical formulations of amyloid inhibiting compounds |
| JP2005272347A (en) * | 2004-03-24 | 2005-10-06 | Ohara Yakuhin Kogyo Kk | Method for producing solid preparation |
| EP1781260B2 (en) | 2004-08-13 | 2014-04-02 | Boehringer Ingelheim International GmbH | Extended release tablet formulation containing pramipexole or a pharmaceutically acceptable salt thereof, method for manufacturing the same and use thereof |
| MX2007001850A (en) | 2004-08-13 | 2007-03-28 | Boehringer Ingelheim Int | Extended release pellet formulation containing pramipexole or a pharmaceutically acceptable salt thereof, method for manufacturing the same and use thereof. |
| EP1970056A1 (en) * | 2007-03-15 | 2008-09-17 | Polichem S.A. | Time-specific delayed/pulsatile release dosage forms |
| US9132096B1 (en) | 2014-09-12 | 2015-09-15 | Alkermes Pharma Ireland Limited | Abuse resistant pharmaceutical compositions |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| ATE269330T1 (en) * | 1989-04-13 | 2004-07-15 | Beecham Group Plc | CHEMICAL COMPOUNDS |
| GB9409718D0 (en) * | 1994-05-14 | 1994-07-06 | Smithkline Beecham Plc | Novel compounds |
| GB9421472D0 (en) * | 1994-10-25 | 1994-12-07 | Smithkline Beecham Plc | Novel methods |
| AR004178A1 (en) * | 1995-07-29 | 1998-11-04 | Smithkline Beecham Plc | PROCEDURE FOR THE FORMULATION OF A PHARMACY, A PHARMACEUTICAL COMPOSITION OBTAINABLE THROUGH THIS PROCEDURE AND THE USE OF THE SAME. |
-
1996
- 1996-09-12 GB GBGB9619074.9A patent/GB9619074D0/en active Pending
-
1997
- 1997-09-08 JP JP10513352A patent/JP2001500150A/en active Pending
- 1997-09-08 TR TR1999/00505T patent/TR199900505T2/xx unknown
- 1997-09-08 IL IL12878197A patent/IL128781A0/en unknown
- 1997-09-08 WO PCT/GB1997/002418 patent/WO1998010762A2/en not_active Application Discontinuation
- 1997-09-08 CZ CZ99832A patent/CZ83299A3/en unknown
- 1997-09-08 NZ NZ334268A patent/NZ334268A/en unknown
- 1997-09-08 PL PL97332074A patent/PL332074A1/en unknown
- 1997-09-08 HU HU9904401A patent/HUP9904401A3/en unknown
- 1997-09-08 AU AU41288/97A patent/AU724086B2/en not_active Ceased
- 1997-09-08 BR BR9711734A patent/BR9711734A/en unknown
- 1997-09-08 EP EP97939064A patent/EP0929301A2/en not_active Withdrawn
- 1997-09-08 KR KR1019997002030A patent/KR20000036039A/en not_active Application Discontinuation
- 1997-09-08 CN CN97199411A patent/CN1235544A/en active Pending
- 1997-09-08 CA CA002265661A patent/CA2265661A1/en not_active Abandoned
- 1997-09-09 CO CO97052280A patent/CO5031291A1/en unknown
- 1997-09-10 ZA ZA978133A patent/ZA978133B/en unknown
- 1997-09-10 AR ARP970104130A patent/AR008176A1/en not_active Application Discontinuation
- 1997-09-10 MA MA24792A patent/MA24359A1/en unknown
- 1997-09-10 PE PE1997000805A patent/PE2499A1/en not_active Application Discontinuation
- 1997-09-10 ID IDP973137A patent/ID19589A/en unknown
-
1999
- 1999-03-11 NO NO991194A patent/NO991194L/en unknown
-
2003
- 2003-01-23 CN CN03102977A patent/CN1446535A/en active Pending
Also Published As
| Publication number | Publication date |
|---|---|
| GB9619074D0 (en) | 1996-10-23 |
| AR008176A1 (en) | 1999-12-09 |
| KR20000036039A (en) | 2000-06-26 |
| NZ334268A (en) | 2000-10-27 |
| HUP9904401A3 (en) | 2001-03-28 |
| CO5031291A1 (en) | 2001-04-27 |
| IL128781A0 (en) | 2000-01-31 |
| WO1998010762A2 (en) | 1998-03-19 |
| NO991194D0 (en) | 1999-03-11 |
| PL332074A1 (en) | 1999-08-30 |
| CN1235544A (en) | 1999-11-17 |
| EP0929301A2 (en) | 1999-07-21 |
| CZ83299A3 (en) | 1999-08-11 |
| NO991194L (en) | 1999-03-11 |
| PE2499A1 (en) | 1999-03-24 |
| BR9711734A (en) | 1999-08-24 |
| TR199900505T2 (en) | 1999-06-21 |
| ID19589A (en) | 1998-07-23 |
| MA24359A1 (en) | 1998-07-01 |
| WO1998010762A3 (en) | 1998-06-04 |
| CA2265661A1 (en) | 1998-03-19 |
| AU4128897A (en) | 1998-04-02 |
| ZA978133B (en) | 1999-04-12 |
| AU724086B2 (en) | 2000-09-14 |
| JP2001500150A (en) | 2001-01-09 |
| CN1446535A (en) | 2003-10-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| HUP9904401A2 (en) | Controlled release dosage form of [r-(z)]-alpha-(methoxyimino)-alpha-(1-azabicyclo[2.2.2]oct-3-yl)acetonitrile monohydrochloride | |
| US4935429A (en) | Method of treating psychostimulant addiction | |
| GR3022459T3 (en) | Quinuclidine derivative as substance p antagonist. | |
| JP2002502871A5 (en) | ||
| NO20022014L (en) | A solid oral controlled release dosage form containing hydrocodone | |
| CA2601289A1 (en) | Once-a-day oxycodone formulations | |
| BR0010498A (en) | Modern drug compositions based on anticholinergically active and beta-mimetic compounds | |
| EP0377272A3 (en) | Use of nalmefene or naltrexone in the manufacture of a medicament for the treatment of inflammation in an arthritic disease or associated inflammatory diseases | |
| JP2002530300A (en) | Dosage formulations for acetylcholinesterase inhibitors | |
| EE200100161A (en) | Slow-release multiparticulates and processes for their preparation | |
| JPS59193821A (en) | Use of fluoxetin as antianxiety | |
| Pisania et al. | Single dose pharmacokinetics of carbamazepine-10, 11-epoxide in patients on lamotrigine monotherapy | |
| CA1277914C (en) | Use of dopamine agonists | |
| HUP0204391A2 (en) | The use of mirtazapine for the preparation of pharmaceutical composition suitable for the treatment of sleep disorders | |
| EP0764025B1 (en) | Method and medicine for alleviating jet lag | |
| CA2017619C (en) | Use of naftopidil for the therapy of dysuria in cases of benign prostatic hypertrophy | |
| DE69526102T2 (en) | USE OF [R- (Z)] - ALPHA- (METHOXYIMINO) -ALPHA- (1-AZABICYCLO [2.2.2.] OCT-3-YL) ACETONITRILE FOR INHIBITING AMYLOID BETA A4 FORMATION IN ALZHEIMER'S DISEASE | |
| HUP9701060A2 (en) | Pharmaceutical composition containing darifenacin for treating cognitive disturbs | |
| HUP0401798A2 (en) | Use of rosuvastatin for preparation of pharmaceutical compositions usable in pre demented states | |
| JPH045231A (en) | Analgesic for chronic pain | |
| HUP0103149A2 (en) | Pharmaceutical composition for treatment of alzheimer's disease | |
| SHAPIRO | Cimetidine-imipramine interaction: case report and comments | |
| NO953072L (en) | Use of inhibitors of ornithine aminotransferase for the manufacture of a medicament for the treatment of Alzheimer's disease | |
| Kaarela et al. | The effect of different indomethacin formulations in young and elderly patients: a comparative controlled clinical trial | |
| GEP20043356B (en) | Compounds Useful For Treatment or Prevention of Diseases Mediated By Alpha- 2B-Adrenoceptor |