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
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P25/00—Drugs for disorders of the nervous system
• • 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
  • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
• • 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
  • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
  • A61P25/16—Anti-Parkinson drugs
• • 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

Definitions

• the present invention relates to the use of l- [4- (3-trifluoromethylphenyl) - 1,2,3,6-tetrahydropyrid-1-yl] -2- (6,7-dimethoxynapht-2-yl) ethane (I ) for the preparation of drugs intended for the treatment and / or prophylaxis of cerebral and neuronal diseases.
• EP 0 458 696 describes the use of 1- [2- (2-naphthyl) ethyl] -4- (3-trifluoromethylphenyl) -1,2,3,6-tetrahydropyridine for the preparation of medicaments intended for the treatment of neurodegeneration.
• the compound of formula (I) and its pharmaceutically acceptable salts have the capacity to increase the survival of neurons.
• the present invention therefore relates to the use of l- [4- (3-trifluoromethylphenyl) -1, 2,3,6-tetrahydropyrid-1-yl] -2- (6,7-dimethoxynapht-2-yl) ethane, of formula (I)
• pharmaceutically acceptable salts of the compound of formula (I) mention may be made of those formed with pharmaceutically acceptable acids, for example, those with mineral acids, such as the hydrochloride, hydrobromide, borate, phosphate, sulphate, hydrogen sulfate, hydrogen phosphate and those with organic acids, such as citrate, benzoate, ascorbate, methyl sulfate, naphthalene-2-sulfonate, picrate, fumarate, maleate, malonate, oxalate, the succinate, acetate, tartrate, mesylate, tosylate, isethionate, ⁇ -ketoglutarate, ⁇ -glycerophosphate, glucose-1-phosphate.
• mineral acids such as the hydrochloride, hydrobromide, borate, phosphate, sulphate, hydrogen sulfate, hydrogen phosphate
• organic acids such as citrate, benzoate, ascorbate, methyl sulfate, naphthal
• the septal region was removed from embryos of 17-18 day old rats under a dissecting microscope under sterile conditions, then it was dissociated in a trypsin-ethylenediaminotetraacetic acid (EDTA) medium.
• EDTA trypsin-ethylenediaminotetraacetic acid
• neuroblasts are then seeded in the wells of a titration plate at the rate of 17x10 cells / cm ⁇ , in a non-serum culture medium consisting of
• test compounds are dissolved in dimethylsulfoxide (DMSO) and diluted as required by the culture medium.
• DMSO dimethylsulfoxide
• the neuroblasts are kept in plates containing the test compound or the corresponding solvent for 4 days without changing the medium.
• the medium is replaced by a tetrazolium salt dissolved in the culture medium (0.15 mg / ml).
• the cells are then placed in an oven at 37 ° C for 4 hours.
• the mitochondrial succinodehydrogenases of living cells reduce the tetrazolium salt to formazan blue, which, after dissolution in DMSO, measures the optical density at 540nm, a density which is linearly correlated with the number of living cells (Manthorpe et al., Dev. Brain Res ., 1988, 25: 191-198).
• the compound of formula (I) as well as its pharmaceutically acceptable addition salts and its solvates can be used for the preparation of pharmaceutical compositions indicated in the treatment and / or prophylaxis of all diseases which involve neuronal degeneration. More particularly, the compounds of the invention can be used, alone or in co-administration or association with other active ingredients acting on the CNS, for example selective M1 cholinomimetics, antagonists
• nootropics such as piracetam, in particular in the following indications: memory disorders, vascular dementia, post-encephalitic disorders, post-apoplectic disorders, post-traumatic syndromes due to a cranial trauma, disorders deriving from cerebral anoxia, Alzheimer's disease, senile dementia, subcortical dementia, such as Huntington's chorea and Parkinson's disease, dementia caused by AIDS, neuropathies derived from morbidity or damage to the sympathetic or sensory nerves, and brain diseases, such as edema cerebral, and the spinocerebellar degenerations, the degenerations of the motor neurons, like for example amiotrophic lateral sclerosis.
• the administration of the compounds of the invention can be suitably carried out by oral, parenteral, sublingual or transdermal route.
• the quantity of active principle to be administered in the treatment of cerebral and neuronal disorders according to the method of the present invention depends on the nature and the gravity of the affections to be treated as well as on the weight of the patients. Nevertheless, the preferred unit doses will generally comprise from 0.5 to 700 mg, advantageously from 2 to 300 mg, preferably from 5 to 150 mg, for example between 5 and 50 mg, namely 1, 2, 5, 10, 15 , 20, 25, 30, 40 or 50 mg of product.
• unit doses will normally be administered one or more times a day, for example 2, 3, 4, or 5 times a day, preferably one to three times a day, the overall dose in humans being variable between 0.5 and 1400 mg per day, advantageously between 1 and 1000 mg per day, for example from 2 to 500 mg, more suitably from 5 to 200 mg per day.
• the active principle can be administered in unit administration forms, either as it is, for example in lyophilized form, either in admixture with conventional pharmaceutical carriers, animals and humans for the treatment of the above conditions.
• Suitable unit administration forms include oral forms such as optionally scored tablets, capsules, powders, granules and oral solutions or suspensions, sublingual and oral administration forms, administration forms under - cutaneous, intramuscular or intravenous, forms of local administration and forms of rectal administration.
• the main active ingredient is mixed with a pharmaceutical carrier such as gelatin, starch, lactose, magnesium stearate, talc, gum arabic or the like.
• a pharmaceutical carrier such as gelatin, starch, lactose, magnesium stearate, talc, gum arabic or the like.
• the tablets can be coated with sucrose or other suitable materials or they can be treated so that they have a prolonged or delayed activity and that they continuously release a predetermined quantity of active principle.
• a preparation in capsules is obtained by mixing the active ingredient with a diluent and by pouring the mixture obtained into soft or hard capsules.
• a preparation in the form of a syrup or elixir may contain the active ingredient together with a sweetener, preferably calorie-free, methylparaben and propylparaben as antiseptics, as well as a flavoring agent and an appropriate color.
• a sweetener preferably calorie-free, methylparaben and propylparaben as antiseptics, as well as a flavoring agent and an appropriate color.
• Water dispersible powders or granules may contain the active ingredient in admixture with dispersing agents or wetting agents, or suspending agents, such as polyvinylpyrrolidone, as well as with sweeteners or correctors taste.
• Suppositories are used for rectal administration which are prepared with binders that melt at rectal temperature, for example cocoa butter or polyethylene glycols.
• aqueous suspensions, saline solutions or sterile injectable solutions which contain pharmacologically compatible dispersing agents and / or wetting agents, for example propylene glycol or butylene glycol.
• the active principle can also be formulated in the form of microcapsules, optionally with one or more carriers or additives.
• the active principle can also be in the form of an inclusion complex in cyclodextrins, their ethers or their esters.

Landscapes

• Health & Medical Sciences (AREA)
• Neurosurgery (AREA)
• Engineering & Computer Science (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Biomedical Technology (AREA)
• Neurology (AREA)
• Public Health (AREA)
• Life Sciences & Earth Sciences (AREA)
• Chemical & Material Sciences (AREA)
• Veterinary Medicine (AREA)
• General Health & Medical Sciences (AREA)
• Medicinal Chemistry (AREA)
• Animal Behavior & Ethology (AREA)
• Pharmacology & Pharmacy (AREA)
• Organic Chemistry (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
• General Chemical & Material Sciences (AREA)
• Chemical Kinetics & Catalysis (AREA)
• Psychology (AREA)
• Psychiatry (AREA)
• Hospice & Palliative Care (AREA)
• Epidemiology (AREA)
• Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
• Hydrogenated Pyridines (AREA)

Priority Applications (14)

Applications Claiming Priority (1)

Publications (1)

Family

ID=9502506

Family Applications (1)

Country Status (11)

Cited By (1)

Citations (3)

• 1997
  • 1997-02-03 HU HU0000767A patent/HUP0000767A3/hu unknown
  • 1997-02-03 EP EP97902426A patent/EP0954311A1/fr not_active Withdrawn
  • 1997-02-03 TR TR1999/01722T patent/TR199901722T2/xx unknown
  • 1997-02-03 CZ CZ992753A patent/CZ275399A3/cs unknown
  • 1997-02-03 JP JP53257498A patent/JP2001511141A/ja active Pending
  • 1997-02-03 EE EEP199900332A patent/EE9900332A/xx unknown
  • 1997-02-03 AU AU16073/97A patent/AU1607397A/en not_active Abandoned
  • 1997-02-03 CA CA002279326A patent/CA2279326A1/fr not_active Abandoned
  • 1997-02-03 WO PCT/FR1997/000202 patent/WO1998033502A1/fr not_active Ceased
  • 1997-02-03 IL IL13099497A patent/IL130994A0/xx unknown
• 1999
  • 1999-07-15 IS IS5117A patent/IS5117A/is unknown

Patent Citations (3)

Non-Patent Citations (2)

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