EP1414423A1 - Agent de traitement de troubles depressifs contenant un anesthesique local - Google Patents
Agent de traitement de troubles depressifs contenant un anesthesique localInfo
- Publication number
- EP1414423A1 EP1414423A1 EP01960129A EP01960129A EP1414423A1 EP 1414423 A1 EP1414423 A1 EP 1414423A1 EP 01960129 A EP01960129 A EP 01960129A EP 01960129 A EP01960129 A EP 01960129A EP 1414423 A1 EP1414423 A1 EP 1414423A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- brain
- substance
- composition according
- nerve cells
- increases
- 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.)
- Withdrawn
Links
- 239000003795 chemical substances by application Substances 0.000 title claims abstract description 25
- 239000003589 local anesthetic agent Substances 0.000 title claims abstract description 17
- 208000020401 Depressive disease Diseases 0.000 title claims abstract description 7
- VYFYYTLLBUKUHU-UHFFFAOYSA-N dopamine Chemical compound NCCC1=CC=C(O)C(O)=C1 VYFYYTLLBUKUHU-UHFFFAOYSA-N 0.000 claims abstract description 80
- 210000004556 brain Anatomy 0.000 claims abstract description 46
- 229960003638 dopamine Drugs 0.000 claims abstract description 40
- 239000000126 substance Substances 0.000 claims abstract description 37
- 210000002569 neuron Anatomy 0.000 claims abstract description 31
- 230000000946 synaptic effect Effects 0.000 claims abstract description 28
- 150000003931 anilides Chemical group 0.000 claims abstract description 12
- 239000004480 active ingredient Substances 0.000 claims abstract description 10
- 239000003814 drug Substances 0.000 claims abstract description 7
- 229960002409 mepivacaine Drugs 0.000 claims description 11
- INWLQCZOYSRPNW-UHFFFAOYSA-N mepivacaine Chemical compound CN1CCCCC1C(=O)NC1=C(C)C=CC=C1C INWLQCZOYSRPNW-UHFFFAOYSA-N 0.000 claims description 10
- WTDRDQBEARUVNC-LURJTMIESA-N L-DOPA Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-LURJTMIESA-N 0.000 claims description 7
- WTDRDQBEARUVNC-UHFFFAOYSA-N L-Dopa Natural products OC(=O)C(N)CC1=CC=C(O)C(O)=C1 WTDRDQBEARUVNC-UHFFFAOYSA-N 0.000 claims description 7
- 229960004502 levodopa Drugs 0.000 claims description 5
- 229960003150 bupivacaine Drugs 0.000 claims description 4
- 229960004194 lidocaine Drugs 0.000 claims description 4
- LEBVLXFERQHONN-UHFFFAOYSA-N 1-butyl-N-(2,6-dimethylphenyl)piperidine-2-carboxamide Chemical compound CCCCN1CCCCC1C(=O)NC1=C(C)C=CC=C1C LEBVLXFERQHONN-UHFFFAOYSA-N 0.000 claims description 3
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 claims description 3
- GMZVRMREEHBGGF-UHFFFAOYSA-N Piracetam Chemical compound NC(=O)CN1CCCC1=O GMZVRMREEHBGGF-UHFFFAOYSA-N 0.000 claims description 3
- DKNWSYNQZKUICI-UHFFFAOYSA-N amantadine Chemical compound C1C(C2)CC3CC2CC1(N)C3 DKNWSYNQZKUICI-UHFFFAOYSA-N 0.000 claims description 3
- 229960003805 amantadine Drugs 0.000 claims description 3
- 229960002802 bromocriptine Drugs 0.000 claims description 3
- OZVBMTJYIDMWIL-AYFBDAFISA-N bromocriptine Chemical compound C1=CC(C=2[C@H](N(C)C[C@@H](C=2)C(=O)N[C@]2(C(=O)N3[C@H](C(N4CCC[C@H]4[C@]3(O)O2)=O)CC(C)C)C(C)C)C2)=C3C2=C(Br)NC3=C1 OZVBMTJYIDMWIL-AYFBDAFISA-N 0.000 claims description 3
- 229960003976 etidocaine Drugs 0.000 claims description 3
- UWCVGPLTGZWHGS-ZORIOUSZSA-N pergolide mesylate Chemical compound CS(O)(=O)=O.C1=CC([C@H]2C[C@@H](CSC)CN([C@@H]2C2)CCC)=C3C2=CNC3=C1 UWCVGPLTGZWHGS-ZORIOUSZSA-N 0.000 claims description 3
- 229960004526 piracetam Drugs 0.000 claims description 3
- 229960001549 ropivacaine Drugs 0.000 claims description 3
- MEZLKOACVSPNER-GFCCVEGCSA-N selegiline Chemical compound C#CCN(C)[C@H](C)CC1=CC=CC=C1 MEZLKOACVSPNER-GFCCVEGCSA-N 0.000 claims description 3
- 229960003946 selegiline Drugs 0.000 claims description 3
- 208000024891 symptom Diseases 0.000 claims description 3
- MIQPIUSUKVNLNT-UHFFFAOYSA-N tolcapone Chemical compound C1=CC(C)=CC=C1C(=O)C1=CC(O)=C(O)C([N+]([O-])=O)=C1 MIQPIUSUKVNLNT-UHFFFAOYSA-N 0.000 claims description 3
- 229960004603 tolcapone Drugs 0.000 claims description 3
- ZKMNUMMKYBVTFN-HNNXBMFYSA-N (S)-ropivacaine Chemical compound CCCN1CCCC[C@H]1C(=O)NC1=C(C)C=CC=C1C ZKMNUMMKYBVTFN-HNNXBMFYSA-N 0.000 claims description 2
- 238000002560 therapeutic procedure Methods 0.000 abstract description 5
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 description 26
- 229940076279 serotonin Drugs 0.000 description 13
- SFLSHLFXELFNJZ-QMMMGPOBSA-N (-)-norepinephrine Chemical compound NC[C@H](O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-QMMMGPOBSA-N 0.000 description 7
- 229960002748 norepinephrine Drugs 0.000 description 7
- SFLSHLFXELFNJZ-UHFFFAOYSA-N norepinephrine Natural products NCC(O)C1=CC=C(O)C(O)=C1 SFLSHLFXELFNJZ-UHFFFAOYSA-N 0.000 description 7
- 229920002527 Glycogen Polymers 0.000 description 5
- 229940096919 glycogen Drugs 0.000 description 5
- 230000000994 depressogenic effect Effects 0.000 description 4
- 229960005015 local anesthetics Drugs 0.000 description 4
- 239000002858 neurotransmitter agent Substances 0.000 description 4
- 230000002889 sympathetic effect Effects 0.000 description 4
- 230000003925 brain function Effects 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000000034 method Methods 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- VTUSIVBDOCDNHS-UHFFFAOYSA-N Etidocaine Chemical compound CCCN(CC)C(CC)C(=O)NC1=C(C)C=CC=C1C VTUSIVBDOCDNHS-UHFFFAOYSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 230000004888 barrier function Effects 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 230000008499 blood brain barrier function Effects 0.000 description 2
- 210000001218 blood-brain barrier Anatomy 0.000 description 2
- -1 butanilicain Chemical compound 0.000 description 2
- 239000008103 glucose Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 230000001734 parasympathetic effect Effects 0.000 description 2
- 230000035699 permeability Effects 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 1
- 208000018737 Parkinson disease Diseases 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 210000000577 adipose tissue Anatomy 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 230000036772 blood pressure Effects 0.000 description 1
- 229960001290 butanilicaine Drugs 0.000 description 1
- VWYQKFLLGRBICZ-UHFFFAOYSA-N butanilicaine Chemical compound CCCCNCC(=O)NC1=C(C)C=CC=C1Cl VWYQKFLLGRBICZ-UHFFFAOYSA-N 0.000 description 1
- 230000002490 cerebral effect Effects 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 230000029087 digestion Effects 0.000 description 1
- 230000002996 emotional effect Effects 0.000 description 1
- 230000006870 function Effects 0.000 description 1
- 229940088597 hormone Drugs 0.000 description 1
- 239000005556 hormone Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 230000035992 intercellular communication Effects 0.000 description 1
- 230000007257 malfunction Effects 0.000 description 1
- 230000010534 mechanism of action Effects 0.000 description 1
- 230000036651 mood Effects 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 230000007433 nerve pathway Effects 0.000 description 1
- 210000000653 nervous system Anatomy 0.000 description 1
- 238000010422 painting Methods 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000011301 standard therapy Methods 0.000 description 1
- 210000003523 substantia nigra Anatomy 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- 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
- A61K31/16—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
-
- 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
- A61P25/24—Antidepressants
-
- 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 invention relates to an agent for the manufacture of a medicament for the treatment of depression.
- depression is usually caused by a depletion of biochemical or messenger substances or neurotransmitters such as dopamine, noradrenaline and serotonin.
- Depression is experienced subjectively by the individuals concerned as a feeling of general powerlessness, this feeling being caused consciously or unconsciously by a restriction of the subjective brain performance. If a person does not consciously perceive a restriction of their own brain performance, a general lack of drive is perceived subjectively compared to other people or also compared to their own earlier phases of life. This results in a feeling of inability to shape one's own life, whereby a life shaped by others is perceived as not meaningful and worth living.
- the triggering element of the subjective emotional basic mood of a depressed person is therefore the feeling or the recognition of a lack of controllability of the environment or one's own powerlessness and the resulting unimportance or superfluousness of one's own person.
- the reason for this, namely the restriction of one's own brain performance, is only perceived personally by some of those affected.
- the object of the invention is therefore to provide an agent with which depression and the symptoms of depression can be effectively treated.
- this object is achieved by a local anesthetic from the anilide group.
- the substance mepivacaine is selected as the local anesthetic of the anilide group, preferably in a daily dose of 30 mg to 60 mg.
- the substances lidocaine, bupivacaine, butanilicaine, tholycaine or etidocaine can be used.
- an activation of the intercellular communication of the cerebral nerve cells of a depressed person is achieved quintessentially by the combination of active ingredients of a substance increasing the dopamine concentration in the synaptic gap of the nerve cells of the brain and a local anesthetic of the anilide group or its derivatives.
- Serotonin plays an important role in depression. Serotonin is the so-called happiness hormone, whereby a person feels happy with a given concentration of serotonin in the brain or at least does not feel depressed. There is an empirical relationship between the serotonin concentration and the dopamine concentration in the brain.
- Depression is particularly attributable to a malfunction of the so-called parasympatic system and / or the sympathetic system of the human brain.
- the parasympathetic system controls the body's energy-building processes such as sleep, digestion and relaxation. It leads to lower blood pressure, heart rate reduction and converts glucose into glycogen. Serotonin is predominantly the neurotransmitter in the parasympathetic system.
- the sympathetic system is used to control energy-consuming processes such as heart activation, increased blood pressure and blood sugar mobilization.
- the neurotransmitter in the sympathetic system is predominantly norepinephrine.
- Adequate provision of a concentration of dopamine, norepinephrine and serotonin in the brain required for normal brain function can be treated according to the invention by targeted administration of a local anesthetic from the anilide group.
- a local anesthetic from the anilide group.
- the permeability of the blood / brain barrier is increased in such a way that L-dopa can increasingly pass through this barrier and get into the brain.
- L-dopa is a substance that is converted to dopamine in the substantia nigra, another area of the brain.
- dopamine is a precursor to the formation of serotonin and norepinephrine.
- the agent according to the invention causes an increase in the transmission potential of the connections of nerve cells, in particular those of the brain.
- the combination of a substance that increases the dopamine concentration in the synaptic gap of the nerve cells of the brain with a local anesthetic from the anilide group causes the permeability of the blood-brain barrier for the substance LevoDopa to be increased, so that dopamine is accumulative in higher concentrations than with current standard therapy in the brain of patients suffering from depression people, which consequently a higher concentration of dopamine in the brain • these persons is reached.
- the substance "local anesthetic of the anilide group" for Parkinson's therapy which is essential to the invention, generally belongs to the local anesthetics of different structure, the local anesthetics of the anilide group and their derivatives being preferred for therapy as a subgroup of these local anesthetics.
- examples of this subgroup are Ropivacaine.
- the smallest molecule in this group has mepivacaine, and this substance has also been shown to be most effective in the treatment of Parkinson's disease patients.
- Mepivacaine is also lipophilic, meaning fat-loving and likes to attach to fat molecules.
- nerve cells are mostly embedded in fat and that the addition or accumulation of mepivacaine in fat is likely to have an impact on the nerve pathways through the fatty tissue.
- LevoDopa like Mepivacaine, also has a strong lipophilicity, so that a possible mechanism of action is also given in this connection.
- In. LevoDopa is preferably applied to the agent according to the invention for the manufacture of a medicament for the treatment of depression in a daily dose of 200 mg to 600 mg.
- the substance which increases the dopamine concentration in the synaptic gap of the nerve cells of the brain additionally contains bromocriptine, which is preferably applied in a daily dose of 1.25 mg to 10 mg.
- the substance which increases the dopamine concentration in the synaptic gap of the nerve cells of the brain additionally contains selegiline, which is preferably administered in a daily dose of 4 mg to 20 mg.
- the substance which increases the dopamine concentration in the synaptic gap of the nerve cells of the brain additionally contains amantadine, which is preferably applied in a daily dose of 100 mg to 400 mg.
- the substance which increases the dopamine concentration in the synaptic gap of the nerve cells of the brain additionally contains pergolide mesilate, which is preferably applied in a daily dose of 2 mg to 8 mg.
- the agent according to the invention can also contain tolcapone as a substance which increases the dopamine concentration in the synaptic cleft of the nerve cells of the brain and is applied in a daily dose of 100 mg to 400 mg.
- the substance which increases the dopamine concentration in the synaptic cleft of the nerve cells of the brain could additionally contain piracetam, which is administered in a daily dose of 1,000 mg to 4,000 mg.
- the effect of the agent according to the invention is less based on a special combination of increasing the dopamine concentration in the synaptic gap of the brain nerve cells
- the indicated doses of local anesthetics are related to injection applications. In the case of oral administration, the dosage must be adjusted accordingly.
Landscapes
- Health & Medical Sciences (AREA)
- Public Health (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Neurosurgery (AREA)
- Engineering & Computer Science (AREA)
- Epidemiology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Pain & Pain Management (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
L'invention concerne un agent servant à produire un médicament destiné au traitement de troubles dépressifs. Selon cette invention, une combinaison de principes actifs, composée d'une substance augmentant la concentration de dopamine dans la fente synaptique des cellules nerveuses du cerveau et d'un anesthésique local du groupe anilide, permet d'obtenir un traitement plus efficace que la thérapie classique.
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/DE2001/002869 WO2003011269A1 (fr) | 2001-07-31 | 2001-07-31 | Agent de traitement des symptomes de la demence contenant un anesthesique local supplementaire |
| PCT/DE2001/002870 WO2003011270A1 (fr) | 2001-07-31 | 2001-07-31 | Agent de traitement de troubles depressifs contenant un anesthesique local |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| EP1414423A1 true EP1414423A1 (fr) | 2004-05-06 |
Family
ID=33030494
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP01960129A Withdrawn EP1414423A1 (fr) | 2001-07-31 | 2001-07-31 | Agent de traitement de troubles depressifs contenant un anesthesique local |
| EP01962579A Withdrawn EP1414424A1 (fr) | 2001-07-31 | 2001-07-31 | Agent de traitement des symptomes de la demence contenant un anesthesique local supplementaire |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| EP01962579A Withdrawn EP1414424A1 (fr) | 2001-07-31 | 2001-07-31 | Agent de traitement des symptomes de la demence contenant un anesthesique local supplementaire |
Country Status (3)
| Country | Link |
|---|---|
| US (1) | US20040192772A1 (fr) |
| EP (2) | EP1414423A1 (fr) |
| WO (2) | WO2003011270A1 (fr) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB0329498D0 (en) | 2003-12-19 | 2004-01-28 | Novartis Ag | Organic compounds |
| EP3008167A4 (fr) * | 2013-06-13 | 2017-06-07 | VeroScience LLC | Compositions et méthodes pour le traitement des troubles métaboliques |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4041174A (en) * | 1974-08-16 | 1977-08-09 | Rom-Amer Pharmaceuticals, Ltd. | Method of treating depression |
| US5064858A (en) * | 1988-08-17 | 1991-11-12 | Spectrum Pharmaceutical Corporation | Protected complex of procaine for the treatment of symptoms from narcotics addiction, tinnitus and Alzheimer's disease |
| US6133299A (en) * | 1993-02-25 | 2000-10-17 | Warner-Lambert Company | Methods for treating neurodegenerative diseases and disorders using N-(2,6-disubstituted aromatic)-N'-pyridinyl ureas and other anticonvulsant compounds |
| NZ311474A (en) * | 1995-06-09 | 1997-09-22 | Euro Celtique Sa | Formulations for providing prolonged local anesthesia |
| US5891885A (en) * | 1996-10-09 | 1999-04-06 | Algos Pharmaceutical Corporation | Method for treating migraine |
| DE19855704C2 (de) * | 1998-12-03 | 2002-08-01 | Lothar Saiger | Verwendung einer Wirkstoffkombination zur Behandlung der Parkinsonschen Krankheit |
-
2001
- 2001-07-31 WO PCT/DE2001/002870 patent/WO2003011270A1/fr not_active Ceased
- 2001-07-31 WO PCT/DE2001/002869 patent/WO2003011269A1/fr not_active Ceased
- 2001-07-31 EP EP01960129A patent/EP1414423A1/fr not_active Withdrawn
- 2001-07-31 EP EP01962579A patent/EP1414424A1/fr not_active Withdrawn
-
2004
- 2004-01-28 US US10/766,537 patent/US20040192772A1/en not_active Abandoned
Non-Patent Citations (1)
| Title |
|---|
| See references of WO03011270A1 * |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2003011270A1 (fr) | 2003-02-13 |
| EP1414424A1 (fr) | 2004-05-06 |
| US20040192772A1 (en) | 2004-09-30 |
| WO2003011269A1 (fr) | 2003-02-13 |
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Legal Events
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| 18D | Application deemed to be withdrawn |
Effective date: 20060607 |