WO1997017074A1 - Treatment of traumatic brain injury - Google Patents
Treatment of traumatic brain injury Download PDFInfo
- Publication number
- WO1997017074A1 WO1997017074A1 PCT/DK1996/000458 DK9600458W WO9717074A1 WO 1997017074 A1 WO1997017074 A1 WO 1997017074A1 DK 9600458 W DK9600458 W DK 9600458W WO 9717074 A1 WO9717074 A1 WO 9717074A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- treatment
- tetrahydro
- ethyl
- tetrazol
- traumatic brain
- Prior art date
Links
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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
-
- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
-
- 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
- A61P25/04—Centrally acting analgesics, e.g. opioids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
Definitions
- EP-A1 0 296 721 disclosed a class of piperidine or 1 ,2,3,6-terahydropyridine com ⁇ pounds substituted in the 5-position with a five-membered heterocyclic group includ ⁇ ing a subclass of optionally substituted 5-tetrazolyl-1 ,2,3,6-tetrahydro-pyridine com ⁇ pounds.
- the compounds were disclosed to have high affinity to central cholinergic receptors, in particular high affinity for central muscarinic Mi receptors, thus being useful in the treatment of Alzheimer's disease, senile dementia, and impaired learning and memory functions.
- traumatic brain injury is in this specification meant to include all conditions associated with trauma to the brain or spinal cord e.g. caused by physical forces acting on the scull or spinal column, ischaemia, stroke, arrested breathing, cardiac arrest, cerebral thrombosis or embolism, neurological problems caused by AIDS, cerebral hemorrhage, encephalomyelitis, hydrocephalus, post-operative events, cerebral infections, concussions or elevated intracranial pressure.
- Exemplary of such inorganic salts are those with hydrochlo ⁇ ric, hydrobromic, sulfuric, sulfamic, phosphoric and nitric acids.
- the compound used according to the invention has now been found to be useful in the treatment of TBI. So, for example it improves cognitive performance following to moderate traumatic brain injury and it attenuates injury-reduced reductions of cholinergic neurones. Furthermore it has been found not to cause adverse cardiac 5 or other side effects in doses believed to be clinically relevant.
- the present invention provides a method for the prevention or treatment of TBI in man comprising the step of administering a therapeutically effective amount of 5-(2-ethyl-2H-tetrazol-5-yl)-1 ,2,3,6-tetrahydro-1 -methylpyridine io or acid addition salt thereof to a patient in need thereof.
- Rats were subjected to central fluid percussion traumatic brain injury as described by Dixon, C.E., et al., J. Neurosurgery, 67 (1987) 110- 119.
- the injured animals were treated s.c. daily on days 1 -15 postinjury beginning 24 hours after injury with either saline or 5-(2-ethyl-2H-tetrazol-5-yl)-1 , 2, 3, 6-tetrahydro-1 -methylpyridine, 3.6 ⁇ mol/kg or 15 ⁇ mol/kg.
- Free floating forebrain sections were incubated in a final ChAT antibody concentra ⁇ tion (1 :50) of 1.0 ⁇ g/ml in a 0.01 M phosphate buffered saline (PBS) solution contain ⁇ ing 0.1% triton X-100.
- the forebrain sections were trimmed and incubated in the pri- mary antibody for 24 hours at room temperature in culture trays (4 sections/300 ⁇ LJwell).
- the pharmaceutical formulations of the invention may be prepared by conventional methods in the art.
- Typical examples of recipes for the formulations of the invention are as follows (amounts of active ingredient calculated as the free base):
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- Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Pain & Pain Management (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
Abstract
Description
Claims
Priority Applications (13)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
BR9611396A BR9611396A (en) | 1995-11-06 | 1996-11-05 | Compound for treatment of traumatic brain injury |
KR1019980703360A KR19990067353A (en) | 1995-11-06 | 1996-11-05 | Brain damage caused by trauma |
HU9901051A HUP9901051A2 (en) | 1995-11-06 | 1996-11-05 | Use of 5-(2-ethyl-2h-tetrazol-5-il)-1,2,3,6-tetrahydro-1-methyl-pyridine for the manufacture of pharmaceutical preparations for the treatment of traumatic brain injury |
EA199800434A EA000531B1 (en) | 1995-11-06 | 1996-11-05 | Active substance for production of pharmaceutical preparation for treatment of traumatic brain injury |
NZ321546A NZ321546A (en) | 1995-11-06 | 1996-11-05 | Treatment of traumatic brain injury using 5-(2-ethyl-2H-tetrazol-5-yl)-1,2,3,6-tetrahydro-1-methylpyridine |
PL96326490A PL326490A1 (en) | 1995-11-06 | 1996-11-05 | Treatment of traumatic brain injuries |
AU74900/96A AU706594B2 (en) | 1995-11-06 | 1996-11-05 | Treatment of traumatic brain injury |
EP96937193A EP0866706A1 (en) | 1995-11-06 | 1996-11-05 | Treatment of traumatic brain injury |
JP9517762A JPH11514654A (en) | 1995-11-06 | 1996-11-05 | How to treat brain injury due to trauma |
SK581-98A SK58198A3 (en) | 1995-11-06 | 1996-11-05 | Treatment of traumatic brain injury |
IS4726A IS4726A (en) | 1995-11-06 | 1998-04-27 | Treatment of brain damage due to trauma |
NO982036A NO982036L (en) | 1995-11-06 | 1998-05-05 | A compound suitable for the treatment of traumatic brain injury |
BG102480A BG63150B1 (en) | 1995-11-06 | 1998-05-22 | Method for the treatment of traumatic cerebral impairment |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DK1232/95 | 1995-11-06 | ||
DK123295 | 1995-11-06 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1997017074A1 true WO1997017074A1 (en) | 1997-05-15 |
Family
ID=8102484
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/DK1996/000458 WO1997017074A1 (en) | 1995-11-06 | 1996-11-05 | Treatment of traumatic brain injury |
Country Status (18)
Country | Link |
---|---|
EP (1) | EP0866706A1 (en) |
JP (1) | JPH11514654A (en) |
KR (1) | KR19990067353A (en) |
AU (1) | AU706594B2 (en) |
BG (1) | BG63150B1 (en) |
BR (1) | BR9611396A (en) |
CA (1) | CA2234824A1 (en) |
CZ (1) | CZ287441B6 (en) |
EA (1) | EA000531B1 (en) |
HU (1) | HUP9901051A2 (en) |
IS (1) | IS4726A (en) |
NO (1) | NO982036L (en) |
NZ (1) | NZ321546A (en) |
PL (1) | PL326490A1 (en) |
SK (1) | SK58198A3 (en) |
TR (1) | TR199800801T2 (en) |
WO (1) | WO1997017074A1 (en) |
ZA (1) | ZA969320B (en) |
Cited By (9)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1999001448A1 (en) * | 1997-07-01 | 1999-01-14 | H. Lundbeck A/S | 5-(2-ethyl-2h-tetrazol-5-y1)-1-methyl-1,2,3,6-tetrahydropyridine maleate |
US7678363B2 (en) | 2005-08-26 | 2010-03-16 | Braincells Inc | Methods of treating psychiatric conditions comprising administration of muscarinic agents in combination with SSRIs |
WO2010099217A1 (en) | 2009-02-25 | 2010-09-02 | Braincells, Inc. | Modulation of neurogenesis using d-cycloserine combinations |
EP2258358A2 (en) | 2005-08-26 | 2010-12-08 | Braincells, Inc. | Neurogenesis with acetylcholinesterase inhibitor |
EP2314289A1 (en) | 2005-10-31 | 2011-04-27 | Braincells, Inc. | Gaba receptor mediated modulation of neurogenesis |
WO2011063115A1 (en) | 2009-11-19 | 2011-05-26 | Braincells Inc. | Combination of nootropic agent with one or more neurogenic or neurogenic sensitizing agents for stimulating or increasing neurogenesis |
WO2011091033A1 (en) | 2010-01-20 | 2011-07-28 | Braincells, Inc. | Modulation of neurogenesis by ppar agents |
EP2377531A2 (en) | 2006-05-09 | 2011-10-19 | Braincells, Inc. | Neurogenesis by modulating angiotensin |
EP2377530A2 (en) | 2005-10-21 | 2011-10-19 | Braincells, Inc. | Modulation of neurogenesis by PDE inhibition |
Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0296721A2 (en) * | 1987-06-24 | 1988-12-28 | H. Lundbeck A/S | Heterocyclic compounds |
EP0525879A1 (en) * | 1991-07-26 | 1993-02-03 | Akzo Nobel N.V. | Pyrazole derivatives |
WO1993019062A1 (en) * | 1992-03-24 | 1993-09-30 | Warner-Lambert Company | Tetrahydropyridine isoxazoline derivatives |
US5328925A (en) * | 1989-02-22 | 1994-07-12 | Novo Nordisk A/S | Piperidine compounds and their use |
-
1996
- 1996-11-05 EA EA199800434A patent/EA000531B1/en not_active IP Right Cessation
- 1996-11-05 EP EP96937193A patent/EP0866706A1/en not_active Ceased
- 1996-11-05 WO PCT/DK1996/000458 patent/WO1997017074A1/en not_active Application Discontinuation
- 1996-11-05 CA CA002234824A patent/CA2234824A1/en not_active Abandoned
- 1996-11-05 AU AU74900/96A patent/AU706594B2/en not_active Ceased
- 1996-11-05 JP JP9517762A patent/JPH11514654A/en active Pending
- 1996-11-05 CZ CZ19981389A patent/CZ287441B6/en not_active IP Right Cessation
- 1996-11-05 KR KR1019980703360A patent/KR19990067353A/en not_active Application Discontinuation
- 1996-11-05 HU HU9901051A patent/HUP9901051A2/en unknown
- 1996-11-05 SK SK581-98A patent/SK58198A3/en unknown
- 1996-11-05 BR BR9611396A patent/BR9611396A/en not_active Application Discontinuation
- 1996-11-05 PL PL96326490A patent/PL326490A1/en unknown
- 1996-11-05 NZ NZ321546A patent/NZ321546A/en unknown
- 1996-11-05 TR TR1998/00801T patent/TR199800801T2/en unknown
- 1996-11-06 ZA ZA969320A patent/ZA969320B/en unknown
-
1998
- 1998-04-27 IS IS4726A patent/IS4726A/en unknown
- 1998-05-05 NO NO982036A patent/NO982036L/en not_active Application Discontinuation
- 1998-05-22 BG BG102480A patent/BG63150B1/en unknown
Patent Citations (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0296721A2 (en) * | 1987-06-24 | 1988-12-28 | H. Lundbeck A/S | Heterocyclic compounds |
US5328925A (en) * | 1989-02-22 | 1994-07-12 | Novo Nordisk A/S | Piperidine compounds and their use |
EP0525879A1 (en) * | 1991-07-26 | 1993-02-03 | Akzo Nobel N.V. | Pyrazole derivatives |
WO1993019062A1 (en) * | 1992-03-24 | 1993-09-30 | Warner-Lambert Company | Tetrahydropyridine isoxazoline derivatives |
Non-Patent Citations (1)
Title |
---|
J. MED. CHEM., Volume 37, 1994, EJNER K. MOLTZEN, et al., "Bioisosteres of Arecoline: 1,2,3,6-Tetrahydro-5-Pyridyl-Substituted and 3-Piperidyl-Substituted Derivatives of Tetrazoles and 1,2,3-Triazoles. Synthesis and Muscarinic Activity", pages 4085-4099. * |
Cited By (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1999001448A1 (en) * | 1997-07-01 | 1999-01-14 | H. Lundbeck A/S | 5-(2-ethyl-2h-tetrazol-5-y1)-1-methyl-1,2,3,6-tetrahydropyridine maleate |
EP2275095A2 (en) | 2005-08-26 | 2011-01-19 | Braincells, Inc. | Neurogenesis by muscarinic receptor modulation |
EP2258358A2 (en) | 2005-08-26 | 2010-12-08 | Braincells, Inc. | Neurogenesis with acetylcholinesterase inhibitor |
EP2258357A2 (en) | 2005-08-26 | 2010-12-08 | Braincells, Inc. | Neurogenesis with acetylcholinesterase inhibitor |
EP2258359A2 (en) | 2005-08-26 | 2010-12-08 | Braincells, Inc. | Neurogenesis by muscarinic receptor modulation with sabcomelin |
US7678363B2 (en) | 2005-08-26 | 2010-03-16 | Braincells Inc | Methods of treating psychiatric conditions comprising administration of muscarinic agents in combination with SSRIs |
EP2275096A2 (en) | 2005-08-26 | 2011-01-19 | Braincells, Inc. | Neurogenesis via modulation of the muscarinic receptors |
EP2377530A2 (en) | 2005-10-21 | 2011-10-19 | Braincells, Inc. | Modulation of neurogenesis by PDE inhibition |
EP2314289A1 (en) | 2005-10-31 | 2011-04-27 | Braincells, Inc. | Gaba receptor mediated modulation of neurogenesis |
EP2377531A2 (en) | 2006-05-09 | 2011-10-19 | Braincells, Inc. | Neurogenesis by modulating angiotensin |
EP2382975A2 (en) | 2006-05-09 | 2011-11-02 | Braincells, Inc. | Neurogenesis by modulating angiotensin |
WO2010099217A1 (en) | 2009-02-25 | 2010-09-02 | Braincells, Inc. | Modulation of neurogenesis using d-cycloserine combinations |
WO2011063115A1 (en) | 2009-11-19 | 2011-05-26 | Braincells Inc. | Combination of nootropic agent with one or more neurogenic or neurogenic sensitizing agents for stimulating or increasing neurogenesis |
WO2011091033A1 (en) | 2010-01-20 | 2011-07-28 | Braincells, Inc. | Modulation of neurogenesis by ppar agents |
Also Published As
Publication number | Publication date |
---|---|
BG102480A (en) | 1999-01-29 |
ZA969320B (en) | 1997-05-30 |
CZ138998A3 (en) | 1998-10-14 |
NO982036L (en) | 1998-06-25 |
BG63150B1 (en) | 2001-05-31 |
SK58198A3 (en) | 1998-10-07 |
EP0866706A1 (en) | 1998-09-30 |
NO982036D0 (en) | 1998-05-05 |
TR199800801T2 (en) | 1998-08-21 |
NZ321546A (en) | 2000-12-22 |
KR19990067353A (en) | 1999-08-16 |
EA000531B1 (en) | 1999-10-28 |
EA199800434A1 (en) | 1998-10-29 |
CA2234824A1 (en) | 1997-05-15 |
AU7490096A (en) | 1997-05-29 |
MX9803432A (en) | 1998-09-30 |
IS4726A (en) | 1998-04-27 |
AU706594B2 (en) | 1999-06-17 |
CZ287441B6 (en) | 2000-11-15 |
BR9611396A (en) | 1999-07-13 |
JPH11514654A (en) | 1999-12-14 |
PL326490A1 (en) | 1998-09-28 |
HUP9901051A2 (en) | 2000-03-28 |
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