DE10149611A1 - Use of beta-adrenoceptor agonists, e.g. reproterol, salmeterol or terbutaline, for restoring and/or maintaining function of damaged nerve cells, e.g. for treatment of neurodegenerative diseases - Google Patents
Use of beta-adrenoceptor agonists, e.g. reproterol, salmeterol or terbutaline, for restoring and/or maintaining function of damaged nerve cells, e.g. for treatment of neurodegenerative diseasesInfo
- Publication number
- DE10149611A1 DE10149611A1 DE10149611A DE10149611A DE10149611A1 DE 10149611 A1 DE10149611 A1 DE 10149611A1 DE 10149611 A DE10149611 A DE 10149611A DE 10149611 A DE10149611 A DE 10149611A DE 10149611 A1 DE10149611 A1 DE 10149611A1
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- Prior art keywords
- encephalopathy
- use according
- day
- amount
- adrenoceptor agonists
- Prior art date
- Legal status (The legal status 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 status listed.)
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- GIIZNNXWQWCKIB-UHFFFAOYSA-N Serevent Chemical compound C1=C(O)C(CO)=CC(C(O)CNCCCCCCOCCCCC=2C=CC=CC=2)=C1 GIIZNNXWQWCKIB-UHFFFAOYSA-N 0.000 title claims description 5
- 230000004770 neurodegeneration Effects 0.000 title claims description 5
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Classifications
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/16—Amides, e.g. hydroxamic acids
- A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
- A61K31/167—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the nitrogen of a carboxamide group directly attached to the aromatic ring, e.g. lidocaine, paracetamol
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- 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
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
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- 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
- A61K31/13—Amines
- A61K31/135—Amines having aromatic rings, e.g. ketamine, nortriptyline
- A61K31/136—Amines having aromatic rings, e.g. ketamine, nortriptyline having the amino group directly attached to the aromatic ring, e.g. benzeneamine
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- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
- A61K31/52—Purines, e.g. adenine
- A61K31/522—Purines, e.g. adenine having oxo groups directly attached to the heterocyclic ring, e.g. hypoxanthine, guanine, acyclovir
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
- C12N5/0602—Vertebrate cells
- C12N5/0618—Cells of the nervous system
- C12N5/0619—Neurons
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- C12N5/00—Undifferentiated human, animal or plant cells, e.g. cell lines; Tissues; Cultivation or maintenance thereof; Culture media therefor
- C12N5/06—Animal cells or tissues; Human cells or tissues
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- C12N5/0618—Cells of the nervous system
- C12N5/0622—Glial cells, e.g. astrocytes, oligodendrocytes; Schwann cells
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Abstract
Description
Die vorliegende Erfindung betrifft die Verwendung von β-Adrenozeptor-Agonisten zur Behandlung von neurodegenerativen Erkrankungen. The present invention relates to the use of β-adrenoceptor agonists for Treatment of neurodegenerative diseases.
Das menschliche Gehirn ist ein hochkompliziertes Organ mit mehr als 100 Milliarden Nervenzellen (= Neuronen) und etwa 10 000 Verschaltungen (= Synapsen) pro Zelle. Das Gehirn ist das Zentralorgan der bewussten und unbewussten Verarbeitung der auf den Körper des Menschen einwirkenden Reize, des Denkens und Fühlens, des zielgerichteten Tuns, des Lernens und der Erinnerung. Eine der wichtigsten Leistungen des menschlichen Gehirns ist die Informationsverarbeitung in Sprache; auch Steuerungszentrale einer Vielzahl von Organfunktionen sowie der Atmung, der Herzfrequenz und der Temperaturregelung. The human brain is a highly complex organ with more than 100 billion Nerve cells (= neurons) and about 10,000 connections (= synapses) per cell. The The brain is the central organ of the conscious and unconscious processing of the brain Human stimuli, thinking and feeling, the targeted Doing, learning and remembering. One of the most important achievements of the human Brain is information processing in language; also control center of a variety of organ functions as well as breathing, heart rate and temperature control.
Es gibt eine Vielzahl von Erkrankungen, die zum Absterben von Nervenzellen und/oder einer Verminderung der Synapsen und somit zu einer Einschränkung der Hirnleistung führen. Beispiele für derartige Krankheitsbilder sind Morbus Alzheimer, zerebrovaskuläre Demenzen, Morbus Parkinson, Morbus Pick, Chorea Huntington, Amyotrophe Lateralsklerose, Lewy- Körper-Demenz, Schlaganfall und Gehirntraumata, wie Contusio und Commotio cerebri sowie Hirn- und Rückenmarksverletzungen bzw. Querschnittsverletzungen, Spina bifida, sowie Erkrankungen des Innenohres, beispielsweise Erkrankungen die mit dem Auftreten eines Tinnitus, wie subakutem oder chronischem Tinnitus, verbunden sind, Hörsturz, Morbus Menière, und Erkrankungen, die mit einer Einschränkung des Hörvermögens oder der Verminderung der Sehkraft verbunden sind etc. Eine klinisch etablierte neuroprotektive Therapie der genannten Krankheitsbilder gibt es bisher nicht. Nach dem Auftreten der Symptome werden lediglich diese, nicht aber deren Ursachen, therapiert. There are a variety of diseases that lead to the death of nerve cells and / or one Decreased synapses and thus reduced brain performance. Examples of such clinical pictures are Alzheimer's disease, cerebrovascular dementias, Parkinson's disease, Pick's disease, Huntington's chorus, amyotrophic lateral sclerosis, Lewy Body dementia, stroke and brain trauma, such as contusio and commotio cerebri as well Brain and spinal cord injuries or cross-sectional injuries, spina bifida, and Diseases of the inner ear, for example disorders associated with the appearance of a Tinnitus, such as subacute or chronic tinnitus, are connected, sudden hearing loss, disease Menière, and diseases with hearing impairment or Decrease in vision, etc. A clinically established neuroprotective So far there is no therapy for the clinical pictures mentioned. After the appearance of the Symptoms are only treated, but not their causes.
Ziel einer kausalen Therapie von Hirnleistungsstörungen ist es, den Untergang von Nervenzellen zu verhindern. The goal of a causal therapy for brain disorders is the demise of To prevent nerve cells.
Derzeit gibt es keine etablierte Therapie, mit der es möglich ist, die Nervenzellen vor Schädigungen zu schützen oder zu regenerieren. Ein wesentliches Element bei der Therapie der oben genannten Krankheiten ist, Schädigungsprozesse an Nervenzellen zu verhindern, die zerebrale Durchblutung zu steigern oder bei Verschluss eines Gefäßes wieder herzustellen, um drohende Schädigungen zu minimieren. Diese Therapieform ist jedoch, wenn überhaupt, nur erfolgreich, wenn sie rasch nach dem akuten Ereignis eingesetzt werden kann. There is currently no established therapy with which it is possible to pre-nerve cells Protect or regenerate damage. An essential element in therapy of the diseases mentioned above is to prevent damage processes to nerve cells, increase cerebral blood flow or when a vessel closes again to minimize the risk of damage. However, this form of therapy is If at all, only successful if used quickly after the acute event can be.
Der vorliegenden Erfindung lag die Aufgabe zugrunde, Arzneistoffe zu finden, die Nervenzellen vor einer Schädigung schützen und die Funktion von partiell oder vollständig degenerierten Zellen zumindest teilweise wiederherstellen können. The present invention was based on the object of finding drugs which Protect nerve cells from damage and the function of partial or complete can at least partially restore degenerated cells.
Überraschenderweise wurde festgestellt, dass durch die Aktivierung von Astrozyten mit Arzneistoffen wie β-Adrenozeptor-Agonisten, endogene Prozesse der Neuroprotektion in Gang gesetzt werden, wodurch die Schädigung bzw. Zerstörung von Nervenzellen vermindert und in einigen Fällen sogar verhindert werden kann. Surprisingly, it was found that the activation of astrocytes with Drugs such as β-adrenoceptor agonists, endogenous processes of neuroprotection in Gear is set, which reduces the damage or destruction of nerve cells and in some cases can even be prevented.
Gegenstand der vorliegenden Erfindung ist demgemäß die Verwendung von β-adrenergen Agonisten zur Wiederherstellung und/oder Aufrechterhaltung der Funktion von partiell oder vollständig durch Enzephalopathie geschädigten Zellen des Zentralnervensystems und/oder anderer Nervenzellen. The present invention accordingly relates to the use of β-adrenergic Agonists to restore and / or maintain the function of partial or cells of the central nervous system and / or completely damaged by encephalopathy other nerve cells.
Im Sinne der vorliegenden Erfindung bedeutet "geschädigte Zelle", daß die Zelle durch äußere Einwirkungen geschädigt wurde oder im Sinne einer Degeneration durch in der Zelle ablaufende Prozesse partiell oder vollständig zerstört wird, was mit einer Beeinträchtigung von Körperfunktionen einhergehen kann. Der Ausdruck "Schädigung der Zelle" umfasst sowohl die Schädigung einzelner Zellen bzw. Zellarten als auch die Schädigung von Strängen oder Bahnen von Nervenzellen. For the purposes of the present invention, "damaged cell" means that the cell is damaged external influences has been damaged or in the sense of degeneration by in the cell running processes is partially or completely destroyed, with an impairment can go hand in hand with bodily functions. The term "cell damage" includes both the damage to individual cells or cell types and the damage to Strands or pathways of nerve cells.
Zu den Nervenzellen zählen neben den Zellen des zentralen Nervensystems auch die Zellen des Rückenmarks und alle weiteren sich im Körper befindenden Nervenzellen. In addition to the cells of the central nervous system, the nerve cells also include the cells of the spinal cord and all other nerve cells in the body.
β-Adrenozeptoren sprechen insbesondere auf adrenerge Arzneistoffe an. Beispiele für β- adrenerge Agonisten, die in der vorliegenden Erfindung wegen ihrer guten Wirksamkeit bevorzugt eingesetzt werden, sind Clenbuterol, Formoterol, Fenoterol, Salbutamol, Orciprenalin, Isoetharine, Cimaterol, Ractopamin, Reproterol, Salmeterol, Terbutalin, deren Isomere, Säure-Additionssalze, Analoga und beliebige Gemische der Voranstehenden. β-adrenoceptors respond in particular to adrenergic drugs. Examples of β- adrenergic agonists in the present invention because of their good potency preferably used are clenbuterol, formoterol, fenoterol, salbutamol, Orciprenaline, Isoetharine, Cimaterol, Ractopamine, Reproterol, Salmeterol, Terbutaline, their Isomers, acid addition salts, analogs and any mixtures of the foregoing.
Auch β1-Adrenozeptor-Agonisten wie Dopamin können Astrozyten aktivieren und dadurch den Schutz der Neurone erreichen. Β1-adrenoceptor agonists such as dopamine can also activate astrocytes and thereby achieve the protection of the neurons.
Anhand von Versuchen konnte beispielsweise nachgewiesen werden, dass die lipophilen β- Adrenozeptor-Agonisten in das Gehirn permeieren können und dort die β-Adrenozeptoren der Astrozyten stimulieren. Die Stimulation dieser Rezeptoren führt wiederum zu einer Aktivierung der Astrozyten und in Folge davon zu einer gesteigerten Freisetzung von Wachstumsfaktoren, wie NGF, welche Nervenzellen vor einer krankheitsbedingten Schädigung schützen können. Experiments have shown, for example, that the lipophilic β- Adrenoceptor agonists can permeate into the brain and there the β-adrenoceptors Stimulate astrocytes. The stimulation of these receptors in turn leads to one Activation of the astrocytes and, as a result, an increased release of Growth factors, such as NGF, which nerve cells before a disease-related Can protect damage.
Die β-Adrenozeptor-Agonisten werden in den für diese Arzneimittel üblichen Mengen appliziert, insbesondere in einer Menge von 0,01 bis 100 mg/Tag, wobei bevorzugte Mengenbereiche auch vom jeweiligen β-Adrenozeptor-Agonisten abhängen können. Mit Substanzen wie Clenbuterol, Formoterol, Fenoterol und Salmeterol wird eine besonders gute neuroprotektive Wirkung erhalten, wenn sie in einer Menge von 0,01 bis 5 mg/Tag verabreicht werden. Terbutalin wird vorzugsweise in einer Menge von 1,0 bis 30 mg/Tag, Salbutamol in einer Menge von 1,0 bis 50 mg/Tag, und Orciprenalin und Reproterol in einer Menge von 1,0 bis 100 mg/Tag appliziert. The β-adrenoceptor agonists are used in the amounts customary for these drugs applied, in particular in an amount of 0.01 to 100 mg / day, preferred Quantity ranges can also depend on the respective β-adrenoceptor agonist. With Substances like clenbuterol, formoterol, fenoterol and salmeterol will be a particularly good one get neuroprotective effect when in an amount of 0.01 to 5 mg / day be administered. Terbutaline is preferably used in an amount of 1.0 to 30 mg / day, Salbutamol in an amount of 1.0 to 50 mg / day, and orciprenaline and reproterol in one Amount applied from 1.0 to 100 mg / day.
Auch β1-Adrenozeptor-Agonisten wie Dobutamin können Astrozyten aktivieren und dadurch einen Schutz der Neurone erreichen. Β1-adrenoceptor agonists such as dobutamine can also activate astrocytes and thereby protect the neurons.
Die erfindungsgemäß verwendeten β-Adrenozeptor-Agonisten sowie ggf. weitere übliche Arzneistoffe, die die Therapie nicht negativ beeinflussen bzw. unterstützen und übliche Inhaltsstoffe, können in pharmazeutisch üblichen Darreichungsformen vorliegen, insbesondere als Lösung, Suspension, Emulsion, Tabletten, Zäpfchen, usw. Auch der Einsatz in Spezialformulierungen wie Liposomen, Nanosomen, Slow-release-pellets etc. ist möglich. Sie können in üblicher Weise, beispielsweise oral, parenteral, intravenös, inhalativ, rectal, intraventriculär, intraarteriell, intraperitoneal und/oder intramusculär oder als Implantat verabreicht werden. Die Art der Verabreichung wird vorzugsweise derart ausgewählt, dass die beeinträchtigten Zellen in schnellstmöglicher Weise von dem erfindungsgemäßen Arzneistoff erreicht werden können. The β-adrenoceptor agonists used according to the invention and possibly other conventional ones Drugs that do not negatively influence or support the therapy and usual ones Ingredients can be in the usual pharmaceutical dosage forms, especially as a solution, suspension, emulsion, tablets, suppositories, etc. Also the Use in special formulations such as liposomes, nanosomes, slow-release pellets etc. possible. You can in the usual way, for example orally, parenterally, intravenously, inhalatively, rectal, intraventricular, intraarterial, intraperitoneal and / or intramuscular or as an implant be administered. The mode of administration is preferably selected such that the affected cells as quickly as possible from the invention Drug can be achieved.
Die erfindungsgemäß verwendeten β-Adrenozeptor-Agonisten eignen sich insbesondere zur Herstellung von Medikamenten für die Behandlung von durch Enzephalopathie verursachten neurodegenerativen Erkrankungen. The β-adrenoceptor agonists used according to the invention are particularly suitable for Manufacture of medicines for the treatment of encephalopathy neurodegenerative diseases.
Die Enzephalopathie zählt zu den krankhaften nicht entzündlichen Hirnveränderungen mit variabler neurologischer und/oder psychischer Symptomatik. Beispiele für Enzephalopathien, die erfindungsgemäß mit β-adrenergen Agonisten behandelt werden können, sind toxische Enzephalopathie, Enzephalopathie diabetica, Enzephalopathie hepatica, Enzephalopathie hypertensiva, metabolische Enzephalopathie, wie durch Stoffwechselstörungen hervorgerufene Enzephalopathie, z. B. bei Enzymopathien, endogenen Störungen, Niereninsuffizienz (auch Enzephalopathie uraemica genannt), Lebererkrankungen, Störungen des Wasser-Elektrolyt- oder Säure-Basen-Haushalts, myklonische infantile Enzephalopathie (Kinsboorne Syndrom), Enzephalopathie postictereca infantum (Bilirubin Enzephalopathie), postkombustionelle Enzephalopathie, Enzephalopathie hervorgerufen durch Schwermetalle, insbesondere durch anorganische und organische Schwermetallverbindungen, wie Verbindungen von Blei, Quecksilber sowie Amalgam, Thallium, Wismut, Aluminium, Nickel sowie beliebige Gemische dieser Verbindungen und der Metallegierungen, toxische Enzephalopathie hervorgerufen durch Alkohol, Enzephalopathie spongiformes bovine (BSE), supcorticale progressive Enzephalopathie, Enzephalopathie traumatica. Encephalopathy is one of the pathological non-inflammatory brain changes variable neurological and / or psychological symptoms. Examples of encephalopathies, which can be treated according to the invention with β-adrenergic agonists are toxic Encephalopathy, encephalopathy diabetica, encephalopathy hepatica, encephalopathy hypertensive, metabolic encephalopathy, such as from metabolic disorders induced encephalopathy, e.g. B. in enzymopathies, endogenous disorders, Renal insufficiency (also called encephalopathy uraemica), liver diseases, disorders of the water-electrolyte or acid-base household, myclonic infantile encephalopathy (Kinsboorne syndrome), encephalopathy postictereca infantum (bilirubin encephalopathy), post-combination encephalopathy, encephalopathy caused by heavy metals, in particular by inorganic and organic heavy metal compounds, such as Compounds of lead, mercury as well as amalgam, thallium, bismuth, aluminum, nickel as well as any mixtures of these compounds and the metal alloys, toxic Encephalopathy caused by alcohol, encephalopathy spongiformes bovine (BSE), supcortical progressive encephalopathy, encephalopathy traumatica.
In einer weiteren Ausführungsform der vorliegenden Erfindung werden die erfindungsgemäß verwendeten Verbindungen zur Prävention für die voranstehend genannten Erkrankungen eingesetzt. In a further embodiment of the present invention, the invention compounds used for prevention of the diseases mentioned above used.
In einer möglichen Ausführungsform der vorliegenden Erfindung werden die β-adrenergen Agonisten in Kombination mit NMDA-Antagonisten eingesetzt. In one possible embodiment of the present invention, the β-adrenergic Agonists used in combination with NMDA antagonists.
Die NMDA-Antagonisten, wie z. B. die Adamantan-Derivate sind bekannte Verbindungen, die vielfach auch zur Behandlung von unterschiedlichen Erkrankungen eingesetzt werden. So ist beispielsweise der dopaminerge Einfluss von Amantadin (1-Adamantanamin) bekannt. The NMDA antagonists, such as. B. the adamantane derivatives are known compounds that often used to treat various diseases. So is for example, the dopaminergic influence of amantadine (1-adamantanamine) is known.
In der europäischen Patentanmeldung EP-392 059 wird die Verwendung von Adamantan- Derivaten zur Prävention und Behandlung der zerebralen Ischämie beschrieben. Gemäß dieser Druckschrift wird durch den Einsatz der Adamantan-Derivate die Zerstörung von Hirnzellen nach einer Ischämie protektiv verhindert, indem die Adamantan-Derivate als Antagonisten für die NMDA-Rezeptorkanäle der Nervenzellen im Gehirn eingesetzt werden. European patent application EP-392 059 describes the use of adamantane Derivatives for the prevention and treatment of cerebral ischemia are described. According to This document describes the destruction of. by using the adamantane derivatives Protective brain cells after ischemia are prevented by using the adamantane derivatives Antagonists are used for the NMDA receptor channels of the nerve cells in the brain.
Bevorzugt werden Adamantanderivate mit der Formel I eingesetzt
in der R1 und R2 gleich oder verschieden sind und für Wasserstoff oder eine geradkettige
oder verzweigte C1-C6-Alkylgruppe stehen oder zusammen mit dem N-Atom eine
heterocyclische Gruppe mit 5 oder 6 Ringatomen darstellen können,
R3 und R4 gleich oder verschieden sind und für Wasserstoff, eine geradkettige oder
verzweigte C1-C6-Alkylgruppe oder eine C5-C6-Cycloalkylgruppe oder eine Vinylgruppe
stehen, und
R5 für Wasserstoff oder eine geradkettige oder verzweigte C1-C6-Alkylgruppe steht.
Adamantane derivatives with the formula I are preferably used
in which R 1 and R 2 are identical or different and represent hydrogen or a straight-chain or branched C 1 -C 6 -alkyl group or together with the N atom can represent a heterocyclic group with 5 or 6 ring atoms,
R 3 and R 4 are identical or different and represent hydrogen, a straight-chain or branched C 1 -C 6 -alkyl group or a C 5 -C 6 -cycloalkyl group or a vinyl group, and
R 5 represents hydrogen or a straight-chain or branched C 1 -C 6 alkyl group.
Die Adamantan-Derivate mit der Formel I können in Form ihrer durch die Formel I beschriebenen Verbindungen oder in Form ihrer pharmazeutisch akzeptablen Salze eingesetzt werden. Zu bevorzugt einsetzbaren pharmazeutisch akzeptablen Salzen zählen die Säure-Additionssalze, wie die Hydrochloride, Hydrobromide, Sulfate, Acetate, Succinate, Tartrate, wobei die Hydrochloride bevorzugt sind. The adamantane derivatives with the formula I can in the form of the formula I described compounds or in the form of their pharmaceutically acceptable salts be used. Preferred pharmaceutically acceptable salts include the acid addition salts, such as the hydrochlorides, hydrobromides, sulfates, acetates, succinates, Tartrate, with the hydrochlorides being preferred.
Bevorzugte Verbindungen mit der Formel I sind diejenigen, in denen R1, R2 und R4 für Wasserstoff und R3 und R5 eine Methyl- und/oder Ethylgruppe sind. Preferred compounds with the formula I are those in which R 1 , R 2 and R 4 are hydrogen and R 3 and R 5 are a methyl and / or ethyl group.
In einer besonders bevorzugten Verbindung stehen R1, R2 und R4 für Wasserstoff und R3 und R5 für einen Methylrest, oder deren Hydrochlorid. Diese Verbindung ist unter dem INN Memantine bekannt. In a particularly preferred compound, R 1 , R 2 and R 4 are hydrogen and R 3 and R 5 are a methyl radical, or their hydrochloride. This connection is known as the INN Memantine.
Claims (8)
Priority Applications (9)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| DE10142175A DE10142175A1 (en) | 2001-10-09 | 2001-08-29 | Use of beta-adrenoceptor agonists, e.g. reproterol, salmeterol or terbutaline, for restoring and/or maintaining function of damaged nerve cells, e.g. for treatment of neurodegenerative diseases |
| DE10149611A DE10149611A1 (en) | 2001-08-29 | 2001-10-09 | Use of beta-adrenoceptor agonists, e.g. reproterol, salmeterol or terbutaline, for restoring and/or maintaining function of damaged nerve cells, e.g. for treatment of neurodegenerative diseases |
| PCT/EP2002/009369 WO2003020257A2 (en) | 2001-08-29 | 2002-08-22 | USE OF β-ADRENOCEPTOR AGONISTS FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES |
| EA200400356A EA200400356A1 (en) | 2001-08-29 | 2002-08-22 | APPLICATION OF β-ADRENORECEPTOR AGONISTS FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES |
| AU2002333510A AU2002333510A1 (en) | 2001-08-29 | 2002-08-22 | Use of beta-adrenoceptor agonists for the treatment of neurodegenerative diseases |
| JP2003524566A JP2005505548A (en) | 2001-08-29 | 2002-08-22 | Methods of using β-adrenergic receptor antagonists for the treatment of neurodegenerative diseases |
| EP02797607A EP1420772A2 (en) | 2001-08-29 | 2002-08-22 | Use of beta-adrenoceptor agonists for the treatment of neurodegenerative diseases |
| PL02373490A PL373490A1 (en) | 2001-08-29 | 2002-08-22 | Use of beta-adrenoceptor agonists for the treatment of neurodegenerative diseases |
| EA200800101A EA200800101A1 (en) | 2001-08-29 | 2002-08-22 | APPLICATION OF β-ADRENORECEPTOR AGONISTS FOR THE TREATMENT OF NEURODEGENERATIVE DISEASES |
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| DE10142175A DE10142175A1 (en) | 2001-10-09 | 2001-08-29 | Use of beta-adrenoceptor agonists, e.g. reproterol, salmeterol or terbutaline, for restoring and/or maintaining function of damaged nerve cells, e.g. for treatment of neurodegenerative diseases |
| DE10149611A DE10149611A1 (en) | 2001-08-29 | 2001-10-09 | Use of beta-adrenoceptor agonists, e.g. reproterol, salmeterol or terbutaline, for restoring and/or maintaining function of damaged nerve cells, e.g. for treatment of neurodegenerative diseases |
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