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):

Landscapes

• 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)

Priority Applications (13)

Applications Claiming Priority (2)

Publications (1)

Family

ID=8102484

Family Applications (1)

Country Status (18)

Cited By (9)

Citations (4)

• 1996
  • 1996-11-05 EA EA199800434A patent/EA000531B1/ru not_active IP Right Cessation
  • 1996-11-05 EP EP96937193A patent/EP0866706A1/de 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/ja active Pending
  • 1996-11-05 CZ CZ19981389A patent/CZ287441B6/cs not_active IP Right Cessation
  • 1996-11-05 KR KR1019980703360A patent/KR19990067353A/ko not_active Application Discontinuation
  • 1996-11-05 HU HU9901051A patent/HUP9901051A2/hu unknown
  • 1996-11-05 SK SK581-98A patent/SK58198A3/sk unknown
  • 1996-11-05 BR BR9611396A patent/BR9611396A/pt not_active Application Discontinuation
  • 1996-11-05 PL PL96326490A patent/PL326490A1/xx unknown
  • 1996-11-05 NZ NZ321546A patent/NZ321546A/xx unknown
  • 1996-11-05 TR TR1998/00801T patent/TR199800801T2/xx unknown
  • 1996-11-06 ZA ZA969320A patent/ZA969320B/xx unknown
• 1998
  • 1998-04-27 IS IS4726A patent/IS4726A/is unknown
  • 1998-05-05 NO NO982036A patent/NO982036L/no not_active Application Discontinuation
  • 1998-05-22 BG BG102480A patent/BG63150B1/bg unknown

Patent Citations (4)

Non-Patent Citations (1)

Also Published As

Similar Documents

Legal Events