WO1997017074A1 - Traitement de lesions traumatiques du cerveau - Google Patents

Traitement de lesions traumatiques du cerveau Download PDF

Info

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
Application number
PCT/DK1996/000458
Other languages
English (en)
Inventor
Brian R. Pike
Original Assignee
H. Lundbeck A/S
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority to JP9517762A priority Critical patent/JPH11514654A/ja
Priority to AU74900/96A priority patent/AU706594B2/en
Priority to PL96326490A priority patent/PL326490A1/xx
Priority to BR9611396A priority patent/BR9611396A/pt
Priority to EA199800434A priority patent/EA000531B1/ru
Priority to SK581-98A priority patent/SK58198A3/sk
Priority to KR1019980703360A priority patent/KR19990067353A/ko
Priority to HU9901051A priority patent/HUP9901051A2/hu
Application filed by H. Lundbeck A/S filed Critical H. Lundbeck A/S
Priority to NZ321546A priority patent/NZ321546A/xx
Priority to EP96937193A priority patent/EP0866706A1/fr
Publication of WO1997017074A1 publication Critical patent/WO1997017074A1/fr
Priority to IS4726A priority patent/IS4726A/is
Priority to NO982036A priority patent/NO982036L/no
Priority to BG102480A priority patent/BG63150B1/bg

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):

Abstract

Cette invention se rapporte au composé 5-(2-éthyl-2H-tétrazol-5-yl)-1,2,3,6-tétrahydro-1-méthylpyridine de formule (I) qui améliore le rendement cognitif et limite les réductions de neurones cholinergiques provoquées par des lésions traumatiques du cerveau. Ce composé sert à la fabrication d'une préparation pharmaceutique destinée au traitement des lésions traumatiques du cerveau.
PCT/DK1996/000458 1995-11-06 1996-11-05 Traitement de lesions traumatiques du cerveau WO1997017074A1 (fr)

Priority Applications (13)

Application Number Priority Date Filing Date Title
KR1019980703360A KR19990067353A (ko) 1995-11-06 1996-11-05 외상으로 인한 뇌 손상 치룡용 의약제제
PL96326490A PL326490A1 (en) 1995-11-06 1996-11-05 Treatment of traumatic brain injuries
BR9611396A BR9611396A (pt) 1995-11-06 1996-11-05 Composto para tratamento de lesão cerebral traumática
EA199800434A EA000531B1 (ru) 1995-11-06 1996-11-05 Активное вещество при производстве фармацевтического препарата для лечения травматического повреждения головного мозга
SK581-98A SK58198A3 (en) 1995-11-06 1996-11-05 Treatment of traumatic brain injury
JP9517762A JPH11514654A (ja) 1995-11-06 1996-11-05 外傷による脳損傷の治療方法
HU9901051A HUP9901051A2 (hu) 1995-11-06 1996-11-05 5-(2-Etil-2H-tetrazol-5-il)-1,2,3,6-tetrahidro-1-metil-piridin alkalmazása traumás agykárosodások kezelésére alkalmas gyógyászati készítmények előállítására
AU74900/96A AU706594B2 (en) 1995-11-06 1996-11-05 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
EP96937193A EP0866706A1 (fr) 1995-11-06 1996-11-05 Traitement de lesions traumatiques du cerveau
IS4726A IS4726A (is) 1995-11-06 1998-04-27 Meðhöndlun á heilaskemmdum vegna áverka
NO982036A NO982036L (no) 1995-11-06 1998-05-05 Forbindelse egnet for behandling av traumatisk hjerneskade
BG102480A BG63150B1 (bg) 1995-11-06 1998-05-22 Метод за лечение на травматично мозъчно увреждане

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
DK123295 1995-11-06
DK1232/95 1995-11-06

Publications (1)

Publication Number Publication Date
WO1997017074A1 true WO1997017074A1 (fr) 1997-05-15

Family

ID=8102484

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/DK1996/000458 WO1997017074A1 (fr) 1995-11-06 1996-11-05 Traitement de lesions traumatiques du cerveau

Country Status (18)

Country Link
EP (1) EP0866706A1 (fr)
JP (1) JPH11514654A (fr)
KR (1) KR19990067353A (fr)
AU (1) AU706594B2 (fr)
BG (1) BG63150B1 (fr)
BR (1) BR9611396A (fr)
CA (1) CA2234824A1 (fr)
CZ (1) CZ287441B6 (fr)
EA (1) EA000531B1 (fr)
HU (1) HUP9901051A2 (fr)
IS (1) IS4726A (fr)
NO (1) NO982036L (fr)
NZ (1) NZ321546A (fr)
PL (1) PL326490A1 (fr)
SK (1) SK58198A3 (fr)
TR (1) TR199800801T2 (fr)
WO (1) WO1997017074A1 (fr)
ZA (1) ZA969320B (fr)

Cited By (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999001448A1 (fr) * 1997-07-01 1999-01-14 H. Lundbeck A/S Maleate de 5-(2-ethyl-2h-tetrazole-5-yl)-1-methyle-1,2,3,6-tetrahydropyridine
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 (fr) 2009-02-25 2010-09-02 Braincells, Inc. Modulation de neurogenèse à l'aide de combinaisons de d-cyclosérine
EP2258357A2 (fr) 2005-08-26 2010-12-08 Braincells, Inc. Neurogenèse avec inhibiteur de l'acetylcholinestérase
EP2314289A1 (fr) 2005-10-31 2011-04-27 Braincells, Inc. Modulation de la neurogenese dont la médiation est assurée par récepteur gaba
WO2011063115A1 (fr) 2009-11-19 2011-05-26 Braincells Inc. Combinaison d'un agent nootropique avec un ou plusieurs agents neurogènes ou à effet neurogène par synergie pour stimuler ou intensifier la neurogenèse
WO2011091033A1 (fr) 2010-01-20 2011-07-28 Braincells, Inc. Modulation de la neurogenèse par des agents ppar
EP2377530A2 (fr) 2005-10-21 2011-10-19 Braincells, Inc. Modulation de neurogénèse par inhibition PDE
EP2377531A2 (fr) 2006-05-09 2011-10-19 Braincells, Inc. Neurogénèse par modulation de l'angiotensine

Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0296721A2 (fr) * 1987-06-24 1988-12-28 H. Lundbeck A/S Composés hétérocycliques
EP0525879A1 (fr) * 1991-07-26 1993-02-03 Akzo Nobel N.V. Dérivés du pyrazole
WO1993019062A1 (fr) * 1992-03-24 1993-09-30 Warner-Lambert Company Derives de tetrahydropyridine isoxazoline
US5328925A (en) * 1989-02-22 1994-07-12 Novo Nordisk A/S Piperidine compounds and their use

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0296721A2 (fr) * 1987-06-24 1988-12-28 H. Lundbeck A/S Composés hétérocycliques
US5328925A (en) * 1989-02-22 1994-07-12 Novo Nordisk A/S Piperidine compounds and their use
EP0525879A1 (fr) * 1991-07-26 1993-02-03 Akzo Nobel N.V. Dérivés du pyrazole
WO1993019062A1 (fr) * 1992-03-24 1993-09-30 Warner-Lambert Company Derives de tetrahydropyridine isoxazoline

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
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)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1999001448A1 (fr) * 1997-07-01 1999-01-14 H. Lundbeck A/S Maleate de 5-(2-ethyl-2h-tetrazole-5-yl)-1-methyle-1,2,3,6-tetrahydropyridine
EP2275096A2 (fr) 2005-08-26 2011-01-19 Braincells, Inc. Neurogenese par modulation des recepteurs muscariniques
EP2258357A2 (fr) 2005-08-26 2010-12-08 Braincells, Inc. Neurogenèse avec inhibiteur de l'acetylcholinestérase
EP2258359A2 (fr) 2005-08-26 2010-12-08 Braincells, Inc. Neurogenèse par modulation des récepteurs muscariniques avec sabcomeline
EP2258358A2 (fr) 2005-08-26 2010-12-08 Braincells, Inc. Neurogenèse avec un inhibiteur de l'acetylcholinestérase
US7678363B2 (en) 2005-08-26 2010-03-16 Braincells Inc Methods of treating psychiatric conditions comprising administration of muscarinic agents in combination with SSRIs
EP2275095A2 (fr) 2005-08-26 2011-01-19 Braincells, Inc. Neurogenese par modulation des recepteurs muscariniques
EP2377530A2 (fr) 2005-10-21 2011-10-19 Braincells, Inc. Modulation de neurogénèse par inhibition PDE
EP2314289A1 (fr) 2005-10-31 2011-04-27 Braincells, Inc. Modulation de la neurogenese dont la médiation est assurée par récepteur gaba
EP2377531A2 (fr) 2006-05-09 2011-10-19 Braincells, Inc. Neurogénèse par modulation de l'angiotensine
EP2382975A2 (fr) 2006-05-09 2011-11-02 Braincells, Inc. Neurogénèse par modulation d'angiotensine
WO2010099217A1 (fr) 2009-02-25 2010-09-02 Braincells, Inc. Modulation de neurogenèse à l'aide de combinaisons de d-cyclosérine
WO2011063115A1 (fr) 2009-11-19 2011-05-26 Braincells Inc. Combinaison d'un agent nootropique avec un ou plusieurs agents neurogènes ou à effet neurogène par synergie pour stimuler ou intensifier la neurogenèse
WO2011091033A1 (fr) 2010-01-20 2011-07-28 Braincells, Inc. Modulation de la neurogenèse par des agents ppar

Also Published As

Publication number Publication date
SK58198A3 (en) 1998-10-07
BG102480A (en) 1999-01-29
AU706594B2 (en) 1999-06-17
BR9611396A (pt) 1999-07-13
BG63150B1 (bg) 2001-05-31
MX9803432A (es) 1998-09-30
CA2234824A1 (fr) 1997-05-15
JPH11514654A (ja) 1999-12-14
HUP9901051A2 (hu) 2000-03-28
CZ287441B6 (en) 2000-11-15
KR19990067353A (ko) 1999-08-16
TR199800801T2 (xx) 1998-08-21
PL326490A1 (en) 1998-09-28
CZ138998A3 (cs) 1998-10-14
EA199800434A1 (ru) 1998-10-29
NO982036L (no) 1998-06-25
EA000531B1 (ru) 1999-10-28
AU7490096A (en) 1997-05-29
EP0866706A1 (fr) 1998-09-30
IS4726A (is) 1998-04-27
ZA969320B (en) 1997-05-30
NZ321546A (en) 2000-12-22
NO982036D0 (no) 1998-05-05

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