WO2000023057A2 - Atypical antiphsychotic in combination with acetylcholinesterase inhibitor for improving cognition - Google Patents
Atypical antiphsychotic in combination with acetylcholinesterase inhibitor for improving cognition Download PDFInfo
- Publication number
- WO2000023057A2 WO2000023057A2 PCT/EP1999/007804 EP9907804W WO0023057A2 WO 2000023057 A2 WO2000023057 A2 WO 2000023057A2 EP 9907804 W EP9907804 W EP 9907804W WO 0023057 A2 WO0023057 A2 WO 0023057A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- atypical antipsychotic
- acetylcholinesterase inhibitor
- patients suffering
- alzheimer
- disease
- Prior art date
Links
- 239000000544 cholinesterase inhibitor Substances 0.000 title claims abstract description 24
- 229940100578 Acetylcholinesterase inhibitor Drugs 0.000 title claims abstract description 19
- 230000019771 cognition Effects 0.000 title claims abstract description 10
- 239000004480 active ingredient Substances 0.000 claims abstract description 26
- 239000003693 atypical antipsychotic agent Substances 0.000 claims abstract description 23
- 239000003112 inhibitor Substances 0.000 claims abstract description 18
- 208000024827 Alzheimer disease Diseases 0.000 claims abstract description 17
- 206010012289 Dementia Diseases 0.000 claims abstract description 17
- 230000000694 effects Effects 0.000 claims abstract description 17
- 230000002411 adverse Effects 0.000 claims abstract description 13
- 208000028017 Psychotic disease Diseases 0.000 claims abstract description 10
- 230000009286 beneficial effect Effects 0.000 claims abstract description 8
- 230000001149 cognitive effect Effects 0.000 claims abstract description 4
- 230000006866 deterioration Effects 0.000 claims abstract description 4
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 4
- 230000002265 prevention Effects 0.000 claims abstract description 4
- 230000002195 synergetic effect Effects 0.000 claims abstract description 4
- ASUTZQLVASHGKV-JDFRZJQESA-N galanthamine Chemical compound O1C(=C23)C(OC)=CC=C2CN(C)CC[C@]23[C@@H]1C[C@@H](O)C=C2 ASUTZQLVASHGKV-JDFRZJQESA-N 0.000 claims description 18
- 238000002360 preparation method Methods 0.000 claims description 13
- 239000003814 drug Substances 0.000 claims description 11
- 229960003980 galantamine Drugs 0.000 claims description 9
- ASUTZQLVASHGKV-UHFFFAOYSA-N galanthamine hydrochloride Natural products O1C(=C23)C(OC)=CC=C2CN(C)CCC23C1CC(O)C=C2 ASUTZQLVASHGKV-UHFFFAOYSA-N 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 8
- 229960001534 risperidone Drugs 0.000 claims description 8
- RAPZEAPATHNIPO-UHFFFAOYSA-N risperidone Chemical compound FC1=CC=C2C(C3CCN(CC3)CCC=3C(=O)N4CCCCC4=NC=3C)=NOC2=C1 RAPZEAPATHNIPO-UHFFFAOYSA-N 0.000 claims description 8
- 239000000203 mixture Substances 0.000 claims description 7
- 229940127236 atypical antipsychotics Drugs 0.000 claims description 6
- 150000002148 esters Chemical class 0.000 claims description 5
- ADEBPBSSDYVVLD-UHFFFAOYSA-N donepezil Chemical compound O=C1C=2C=C(OC)C(OC)=CC=2CC1CC(CC1)CCN1CC1=CC=CC=C1 ADEBPBSSDYVVLD-UHFFFAOYSA-N 0.000 claims description 4
- 230000002708 enhancing effect Effects 0.000 claims description 4
- 208000008454 Hyperhidrosis Diseases 0.000 claims description 3
- 206010028813 Nausea Diseases 0.000 claims description 3
- 208000001431 Psychomotor Agitation Diseases 0.000 claims description 3
- 206010038743 Restlessness Diseases 0.000 claims description 3
- 208000013738 Sleep Initiation and Maintenance disease Diseases 0.000 claims description 3
- 206010047700 Vomiting Diseases 0.000 claims description 3
- 206010022437 insomnia Diseases 0.000 claims description 3
- 230000008693 nausea Effects 0.000 claims description 3
- 230000035900 sweating Effects 0.000 claims description 3
- 230000008673 vomiting Effects 0.000 claims description 3
- PMXMIIMHBWHSKN-UHFFFAOYSA-N 3-{2-[4-(6-fluoro-1,2-benzoxazol-3-yl)piperidin-1-yl]ethyl}-9-hydroxy-2-methyl-6,7,8,9-tetrahydropyrido[1,2-a]pyrimidin-4-one Chemical compound FC1=CC=C2C(C3CCN(CC3)CCC=3C(=O)N4CCCC(O)C4=NC=3C)=NOC2=C1 PMXMIIMHBWHSKN-UHFFFAOYSA-N 0.000 claims description 2
- 208000027776 Extrapyramidal disease Diseases 0.000 claims description 2
- XSVMFMHYUFZWBK-NSHDSACASA-N Rivastigmine Chemical compound CCN(C)C(=O)OC1=CC=CC([C@H](C)N(C)C)=C1 XSVMFMHYUFZWBK-NSHDSACASA-N 0.000 claims description 2
- 206010043118 Tardive Dyskinesia Diseases 0.000 claims description 2
- 229960003530 donepezil Drugs 0.000 claims description 2
- 239000002552 dosage form Substances 0.000 claims description 2
- 229960003162 iloperidone Drugs 0.000 claims description 2
- XMXHEBAFVSFQEX-UHFFFAOYSA-N iloperidone Chemical compound COC1=CC(C(C)=O)=CC=C1OCCCN1CCC(C=2C3=CC=C(F)C=C3ON=2)CC1 XMXHEBAFVSFQEX-UHFFFAOYSA-N 0.000 claims description 2
- 229960005017 olanzapine Drugs 0.000 claims description 2
- KVWDHTXUZHCGIO-UHFFFAOYSA-N olanzapine Chemical compound C1CN(C)CCN1C1=NC2=CC=CC=C2NC2=C1C=C(C)S2 KVWDHTXUZHCGIO-UHFFFAOYSA-N 0.000 claims description 2
- 229960004431 quetiapine Drugs 0.000 claims description 2
- URKOMYMAXPYINW-UHFFFAOYSA-N quetiapine Chemical compound C1CN(CCOCCO)CCN1C1=NC2=CC=CC=C2SC2=CC=CC=C12 URKOMYMAXPYINW-UHFFFAOYSA-N 0.000 claims description 2
- 229960004136 rivastigmine Drugs 0.000 claims description 2
- 238000009097 single-agent therapy Methods 0.000 claims description 2
- 229960000607 ziprasidone Drugs 0.000 claims description 2
- MVWVFYHBGMAFLY-UHFFFAOYSA-N ziprasidone Chemical compound C1=CC=C2C(N3CCN(CC3)CCC3=CC=4CC(=O)NC=4C=C3Cl)=NSC2=C1 MVWVFYHBGMAFLY-UHFFFAOYSA-N 0.000 claims description 2
- 150000007513 acids Chemical class 0.000 description 5
- -1 for example Chemical class 0.000 description 4
- 150000003839 salts Chemical group 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- VKOBVWXKNCXXDE-UHFFFAOYSA-N icosanoic acid Chemical compound CCCCCCCCCCCCCCCCCCCC(O)=O VKOBVWXKNCXXDE-UHFFFAOYSA-N 0.000 description 2
- ISYWECDDZWTKFF-UHFFFAOYSA-N nonadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCCC(O)=O ISYWECDDZWTKFF-UHFFFAOYSA-N 0.000 description 2
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- 229960002024 galantamine hydrobromide Drugs 0.000 description 1
- QORVDGQLPPAFRS-XPSHAMGMSA-N galantamine hydrobromide Chemical compound Br.O1C(=C23)C(OC)=CC=C2CN(C)CC[C@]23[C@@H]1C[C@@H](O)C=C2 QORVDGQLPPAFRS-XPSHAMGMSA-N 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- IPCSVZSSVZVIGE-UHFFFAOYSA-N palmitic acid group Chemical group C(CCCCCCCCCCCCCCC)(=O)O IPCSVZSSVZVIGE-UHFFFAOYSA-N 0.000 description 1
- 125000002958 pentadecyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
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
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- 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
-
- 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
- A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
-
- 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
-
- 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
- the present invention is concerned with pharmaceutical compositions comprising a carrier and as first active ingredient an atypical antipsychotic agent (I) and as second active ingredient an acetylcholinesterase inhibitor (H), each in an amount producing a therapeutically beneficial effect in patients suffering from psychosis, or Alzheimer's disease or related dementias.
- Said therapeutically beneficial effect can be a synergistic effect on the cognitive functioning of patients suffering from Alzheimer's disease or related dementias, or the prevention of the further deterioration of cognition in said patients, or the reduction of adverse effects associated with the one of the active ingredients by the other of the active ingredients.
- an atypical antipsychotic agent (I) for the preparation of a medicament for reducing adverse effects associated with acetylcholinesterase inhibitors (LI) in patients suffering from Alzheimer's disease or related dementias, such as nausea, vomiting, sweating, restlessness and insomnia.
- an atypical antipsychotic agent (I) for the preparation of a medicament for improving sleep in patients suffering from Alzheimer's disease or related dementias while being treated with acetylcholinesterase inhibitors (II).
- the present invention is concerned with a pharmaceutical composition
- a pharmaceutical composition comprising a carrier and as first active ingredient an atypical antipsychotic agent (I) and as second active ingredient an acetylcholinesterase inhibitor (II), each in an amount producing a therapeutically beneficial effect in patients suffering from psychosis, or Alzheimer's disease or related dementias.
- Said therapeutically beneficial effect can be a synergistic effect on the cognitive functioning of patients suffering from Alzheimer's disease or related dementias, or the prevention of the further deterioration of cognition in said patients, or the reduction of adverse effects associated with the one of the active ingredients by the other of the active ingredients.
- the atypical antipsychotic (I) is selected from risperidone, 9-hydroxyrisperidone or a o- 20 alkanoic acid ester thereof, olanzapine, quetiapine, iloperidone or ziprasidone, and the acetylcholinesterase inhibitor (II) is selected from galantamine, rivastigmine or donepezil, or therapeutically active acid addition salt form of any of the foregoing.
- Said salts comprise salt forms which the active ingredients (I) and (H) are able to form with appropriate acids, such as, for example, inorganic acids such as hydrohalic acids, e.g.
- hydrochloric or hydrobromic acid sulfuric; nitric; phosphoric and the like acids; or organic acids such as, for example, acetic, propanoic, hydroxyacetic, lactic, pyruvic, oxalic, malonic, succinic, maleic, fumaric, malic, tartaric, citric, methanesulfonic, ethanesulfonic, benzenesulfonic, -toluenesulfonic, cyclamic, salicylic, p-amino- salicylic, pamoic and the like acids.
- galantamine may conveniently be used as the ( 1 : 1 ) hydrobromide salt.
- a lkanoic acids are selected from the group consisting of decanoic (capric), undecanoic, dodecanoic (lauric), tridecanoic, tetradecanoic (myristic), pentadecanoic, hexadecanoic (palmitic), heptadecanoic, octadecanoic (stearic), nonadecanoic and eicosanoic acid. Due to their limited aqueous solubility, it was generally believed that the esters had to be suspended into oils.
- the ester having a C15 (pentadecyl) chain and the active ingredient corresponding thereto being the 9-hydroxyrisperidone palmitate ester was found to be the superior ester from a pharmacokinetic, as well as from a tolerance point of view.
- the amount of each of the active ingredients is equal to or less than that which is approved in monotherapy with said active ingredient.
- compositions wherein the atypical antipsychotic (I) is risperidone and the acetylcholinesterase inhibitor (II) is galantamine, in particular as galantamine hydrobromide are particularly preferred.
- the amount of risperidone is 0.5, 1, 2, 4, or 6 mg and that of galantamine (as base) is 8, 16, 24 or 32 mg per dosage form.
- the present invention also relates to products containing as first active ingredient an atypical antipsychotic agent (I) and as second active ingredient an acetylcholinesterase inhibitor (II), as combined preparations for simultaneous, separate or sequential use in the treatment of patients suffering from psychosis, Alzheimer's disease or related dementias.
- an atypical antipsychotic agent I
- an acetylcholinesterase inhibitor II
- the present invention also concerns the use of an acetylcholinesterase inhibitor (II) for the preparation of a medicament for enhancing the effect of an atypical antipsychotic agent (I) on cognition in patients suffering from psychosis.
- II acetylcholinesterase inhibitor
- the present invention also concerns the use of an atypical antipsychotic agent (I) for the preparation of a medicament for enhancing the effect of an acetylcholinesterase inhibitor (II) on cognition in patients suffering from Alzheimer's disease or related dementias. Additionally, the present invention concerns the use of an atypical antipsychotic agent
- acetylcholinesterase inhibitors H
- Said adverse effect can be nausea, vomiting, sweating, restlessness or insomnia.
- an atypical antipsychotic agent (I) for the preparation of a medicament for improving sleep in patients suffering from Alzheimer's disease or related dementias while being treated with acetylcholinesterase inhibitors (II).
- the present invention also concerns the use of an acetylcholinesterase inhibitor
- the atypical antipsychotic (I) is preferably risperidone and the acetylcholinesterase inhibitor (II) is preferably galantamine, in particular the (1:1) hydrobromide.
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- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Neurosurgery (AREA)
- Organic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Neurology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biomedical Technology (AREA)
- Epidemiology (AREA)
- Psychiatry (AREA)
- Hospice & Palliative Care (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines Containing Plant Substances (AREA)
Abstract
The present invention is concerned with pharmaceutical compositions comprising a carrier and as first active ingredient an atypical antipsychotic agent (I) and as second active ingredient an acetylcholinesterase inhibitor (II), each in an amount producing a therapeutically beneficial effect in patients suffering from psychosis, or Alzheimer's disease or related dementias. Said therapeutically beneficial effect can be a synergistic effect on the cognitive functioning of patients suffering from Alzheimer's disease or related dementias or the prevention of the further deterioration of cognition in said patients, or the reduction of adverse effects associated with the one of the active ingredients by the other of the active ingredients.
Description
THERAPY FOR IMPROVING COGNITION
The present invention is concerned with pharmaceutical compositions comprising a carrier and as first active ingredient an atypical antipsychotic agent (I) and as second active ingredient an acetylcholinesterase inhibitor (H), each in an amount producing a therapeutically beneficial effect in patients suffering from psychosis, or Alzheimer's disease or related dementias. Said therapeutically beneficial effect can be a synergistic effect on the cognitive functioning of patients suffering from Alzheimer's disease or related dementias, or the prevention of the further deterioration of cognition in said patients, or the reduction of adverse effects associated with the one of the active ingredients by the other of the active ingredients.
Of particular interest is the use of an atypical antipsychotic agent (I) for the preparation of a medicament for reducing adverse effects associated with acetylcholinesterase inhibitors (LI) in patients suffering from Alzheimer's disease or related dementias, such as nausea, vomiting, sweating, restlessness and insomnia. Especially interesting is the use of an atypical antipsychotic agent (I) for the preparation of a medicament for improving sleep in patients suffering from Alzheimer's disease or related dementias while being treated with acetylcholinesterase inhibitors (II).
The present invention is concerned with a pharmaceutical composition comprising a carrier and as first active ingredient an atypical antipsychotic agent (I) and as second active ingredient an acetylcholinesterase inhibitor (II), each in an amount producing a therapeutically beneficial effect in patients suffering from psychosis, or Alzheimer's disease or related dementias. Said therapeutically beneficial effect can be a synergistic effect on the cognitive functioning of patients suffering from Alzheimer's disease or related dementias, or the prevention of the further deterioration of cognition in said patients, or the reduction of adverse effects associated with the one of the active ingredients by the other of the active ingredients.
The atypical antipsychotic (I) is selected from risperidone, 9-hydroxyrisperidone or a o-20 alkanoic acid ester thereof, olanzapine, quetiapine, iloperidone or ziprasidone, and the acetylcholinesterase inhibitor (II) is selected from galantamine, rivastigmine or donepezil, or therapeutically active acid addition salt form of any of the foregoing. Said salts comprise salt forms which the active ingredients (I) and (H) are able to form with appropriate acids, such as, for example, inorganic acids such as hydrohalic acids, e.g. hydrochloric or hydrobromic acid; sulfuric; nitric; phosphoric and the like acids; or
organic acids such as, for example, acetic, propanoic, hydroxyacetic, lactic, pyruvic, oxalic, malonic, succinic, maleic, fumaric, malic, tartaric, citric, methanesulfonic, ethanesulfonic, benzenesulfonic, -toluenesulfonic, cyclamic, salicylic, p-amino- salicylic, pamoic and the like acids. For example, galantamine may conveniently be used as the ( 1 : 1 ) hydrobromide salt.
Cl0-20alkanoic acids are selected from the group consisting of decanoic (capric), undecanoic, dodecanoic (lauric), tridecanoic, tetradecanoic (myristic), pentadecanoic, hexadecanoic (palmitic), heptadecanoic, octadecanoic (stearic), nonadecanoic and eicosanoic acid. Due to their limited aqueous solubility, it was generally believed that the esters had to be suspended into oils. The ester having a C15 (pentadecyl) chain and the active ingredient corresponding thereto being the 9-hydroxyrisperidone palmitate ester was found to be the superior ester from a pharmacokinetic, as well as from a tolerance point of view.
Preferably, the amount of each of the active ingredients is equal to or less than that which is approved in monotherapy with said active ingredient.
Most preferred are compositions wherein the atypical antipsychotic (I) is risperidone and the acetylcholinesterase inhibitor (II) is galantamine, in particular as galantamine hydrobromide. In said compositions, the amount of risperidone is 0.5, 1, 2, 4, or 6 mg and that of galantamine (as base) is 8, 16, 24 or 32 mg per dosage form.
The present invention also relates to products containing as first active ingredient an atypical antipsychotic agent (I) and as second active ingredient an acetylcholinesterase inhibitor (II), as combined preparations for simultaneous, separate or sequential use in the treatment of patients suffering from psychosis, Alzheimer's disease or related dementias.
The present invention also concerns the use of an acetylcholinesterase inhibitor (II) for the preparation of a medicament for enhancing the effect of an atypical antipsychotic agent (I) on cognition in patients suffering from psychosis.
Conversely, the present invention also concerns the use of an atypical antipsychotic agent (I) for the preparation of a medicament for enhancing the effect of an acetylcholinesterase inhibitor (II) on cognition in patients suffering from Alzheimer's disease or related dementias.
Additionally, the present invention concerns the use of an atypical antipsychotic agent
(I) for the preparation of a medicament for reducing adverse effects associated with acetylcholinesterase inhibitors (H) in patients suffering from Alzheimer's disease or related dementias. Said adverse effect can be nausea, vomiting, sweating, restlessness or insomnia. Especially interesting is the use of an atypical antipsychotic agent (I) for the preparation of a medicament for improving sleep in patients suffering from Alzheimer's disease or related dementias while being treated with acetylcholinesterase inhibitors (II).
Finally, the present invention also concerns the use of an acetylcholinesterase inhibitor
(II) for the preparation of a medicament for reducing adverse effects associated with atypical antipsychotic agents (I) in patients suffering from psychoses. Said the adverse effect can be extrapyramidal syndrome or tardive dyskinesia.
In all the preceding uses the atypical antipsychotic (I) is preferably risperidone and the acetylcholinesterase inhibitor (II) is preferably galantamine, in particular the (1:1) hydrobromide.
Claims
1. A pharmaceutical composition comprising a carrier and as first active ingredient an atypical antipsychotic agent (I) and as second active ingredient an acetylcholinesterase inhibitor (II), each in an amount producing a therapeutically beneficial effect in patients suffering from psychosis, Alzheimer's disease or related dementias.
2. A composition according to claim 1 wherein said therapeutically beneficial effect is a synergistic effect on the cognitive functioning of patients suffering from
Alzheimer's disease or related dementias, or the prevention of the further deterioration of cognition in said patients, or the reduction of adverse effects associated with the one of the active ingredients by the other of the active ingredients.
3. A composition according to claim 1 wherein the atypical antipsychotic (I) is selected from risperidone, 9-hydroxyrisperidone or a C10-2o alkanoic acid ester thereof, olanzapine, quetiapine, iloperidone or ziprasidone, and the acetylcholinesterase inhibitor (II) is selected from galantamine, rivastigmine or donepezil.
4. A composition according to claim 3 wherein the amount of each of the active ingredients is equal to or less than that which is approved in monotherapy with said active ingredient.
5. A composition according to claim 3 wherein the atypical antipsychotic (I) is risperidone and the acetylcholinesterase inhibitor (II) is galantamine.
6. A composition according to claim 5 wherein the amount of risperidone is 0.5, 1, 2, 4, or 6 mg and that of galantamine (as base) is 8, 16, 24 or 32 mg per dosage form.
7. A product containing as first active ingredient an atypical antipsychotic agent (I) and as second active ingredient an acetylcholinesterase inhibitor (II), as a combined preparation for simultaneous, separate or sequential use in the treatment of patients suffering from psychosis, Alzheimer's disease or related dementias.
8. The use of an acetylcholinesterase inhibitor (II) for the preparation of a medicament for enhancing the effect of an atypical antipsychotic agent (I) on cognition in patients suffering from psychosis.
9. The use of an atypical antipsychotic agent (I) for the preparation of a medicament for enhancing the effect of an acetylcholinesterase inhibitor (LI) on cognition in patients suffering from Alzheimer's disease or related dementias.
10. The use of an atypical antipsychotic agent (I) for the preparation of a medicament for reducing adverse effects associated with acetylcholinesterase inhibitors (II) in patients suffering from Alzheimer's disease or related dementias.
11. Use according to claim 10 wherein the adverse effect is nausea, vomiting, sweating, restlessness or insomnia.
12. The use of an acetylcholinesterase inhibitor (II) for the preparation of a medicament for reducing adverse effects associated with atypical antipsychotic agents (I) in patients suffering from psychoses.
13. Use according to claim 12 wherein the adverse effect is extrapyramidal syndrome or tardive dyskinesia.
14. Use according to any one of claims 8 to 13 wherein the atypical antipsychotic (I) is risperidone and the acetylcholinesterase inhibitor (LI) is galantamine.
Priority Applications (15)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| IL14258899A IL142588A0 (en) | 1998-10-16 | 1999-10-12 | Therapy for improving cognition |
| SK459-2001A SK4592001A3 (en) | 1998-10-16 | 1999-10-12 | Atypical antipsychotic in combination with acetylcholinesterase inhibitor for improving cognition |
| HU0103781A HUP0103781A3 (en) | 1998-10-16 | 1999-10-12 | Pharmaceutical compositions comprising atypical antiphsychotic agent in combination with acetylcholinesterase inhibitor for improving cognition |
| KR1020017002286A KR20010072878A (en) | 1998-10-16 | 1999-10-12 | Atypical antiphsychotic in combination with acetylcholinesterase inhibitor for improving cognition |
| AU64727/99A AU6472799A (en) | 1998-10-16 | 1999-10-12 | Therapy for improving cognition |
| BR9914419-0A BR9914419A (en) | 1998-10-16 | 1999-10-12 | Perception improvement therapy |
| EEP200100136A EE200100136A (en) | 1998-10-16 | 1999-10-12 | Use of an acetylcholine esterase inhibitor and an antipsychotic agent in the manufacture of a medicament for the treatment of cognitive and psychotic disorders, and a pharmaceutical composition containing these agents |
| JP2000576832A JP2002527469A (en) | 1998-10-16 | 1999-10-12 | Therapy to improve cognition |
| PL99348107A PL348107A1 (en) | 1998-10-16 | 1999-10-12 | Therapy for improving cognition |
| EP99952580A EP1121131A2 (en) | 1998-10-16 | 1999-10-12 | Atypical antipsychotic in combination with acetylcholinesterase inhibitor for improving cognition |
| CA002345767A CA2345767A1 (en) | 1998-10-16 | 1999-10-12 | Therapy for improving cognition |
| BG105302A BG105302A (en) | 1998-10-16 | 2001-03-01 | Means for improving cognition |
| NO20011403A NO20011403L (en) | 1998-10-16 | 2001-03-20 | Therapy to improve congestion |
| HR20010262A HRP20010262A2 (en) | 1998-10-16 | 2001-04-10 | Therapy for improving cognition |
| HK02100158.6A HK1039745A1 (en) | 1998-10-16 | 2002-01-10 | Atypical antipsychotic in combination with acetylcholinesterase inhibitor for improving cognition |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP98203454 | 1998-10-16 | ||
| EP98203454.8 | 1998-10-16 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO2000023057A2 true WO2000023057A2 (en) | 2000-04-27 |
| WO2000023057A3 WO2000023057A3 (en) | 2000-07-27 |
Family
ID=8234219
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/EP1999/007804 WO2000023057A2 (en) | 1998-10-16 | 1999-10-12 | Atypical antiphsychotic in combination with acetylcholinesterase inhibitor for improving cognition |
Country Status (20)
| Country | Link |
|---|---|
| EP (1) | EP1121131A2 (en) |
| JP (1) | JP2002527469A (en) |
| KR (1) | KR20010072878A (en) |
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| WO2004084905A2 (en) * | 2003-03-24 | 2004-10-07 | University Of Florida | Use of 5-ht2c receptor activity affecting compounds for treating idiopathic hyperhidrosis and associated conditions |
| JP2005508975A (en) * | 2001-10-30 | 2005-04-07 | ノバルティス アクチエンゲゼルシャフト | Depot formulation of iloperidone and star polymer |
| WO2005065645A2 (en) * | 2003-12-31 | 2005-07-21 | Actavis Group Hf | Donepezil formulations |
| AU2002231766B2 (en) * | 2001-02-05 | 2005-12-22 | Novartis Ag | New use of iloperidone |
| AU2006201188B2 (en) * | 2001-02-05 | 2007-11-15 | Novartis Ag | New use of iloperidone |
| WO2008055945A1 (en) | 2006-11-09 | 2008-05-15 | Probiodrug Ag | 3-hydr0xy-1,5-dihydr0-pyrr0l-2-one derivatives as inhibitors of glutaminyl cyclase for the treatment of ulcer, cancer and other diseases |
| WO2008065141A1 (en) | 2006-11-30 | 2008-06-05 | Probiodrug Ag | Novel inhibitors of glutaminyl cyclase |
| WO2008104580A1 (en) | 2007-03-01 | 2008-09-04 | Probiodrug Ag | New use of glutaminyl cyclase inhibitors |
| WO2009011560A1 (en) * | 2007-07-16 | 2009-01-22 | Espinosa Abdala Leopoldo De Je | Pharmaceutical composition combining risperidone and donepezil, and use thereof for treating psychotic disorders such as schizophrenia and dimentias such as alzheimer's disease |
| WO2011100373A1 (en) | 2010-02-09 | 2011-08-18 | The Johns Hopkins University | Methods and compositions for improving cognitive function |
| WO2011107530A2 (en) | 2010-03-03 | 2011-09-09 | Probiodrug Ag | Novel inhibitors |
| WO2011110613A1 (en) | 2010-03-10 | 2011-09-15 | Probiodrug Ag | Heterocyclic inhibitors of glutaminyl cyclase (qc, ec 2.3.2.5) |
| WO2011131748A2 (en) | 2010-04-21 | 2011-10-27 | Probiodrug Ag | Novel inhibitors |
| US8227488B2 (en) | 2002-07-15 | 2012-07-24 | Novartis Ag | Injectable depot formulation comprising crystals of iloperidone |
| WO2012123563A1 (en) | 2011-03-16 | 2012-09-20 | Probiodrug Ag | Benz imidazole derivatives as inhibitors of glutaminyl cyclase |
| WO2014144801A1 (en) | 2013-03-15 | 2014-09-18 | Agenebio Inc. | Methods and compositions for improving cognitive function |
| EP2865670A1 (en) | 2007-04-18 | 2015-04-29 | Probiodrug AG | Thiourea derivatives as glutaminyl cyclase inhibitors |
| US10154988B2 (en) | 2012-11-14 | 2018-12-18 | The Johns Hopkins University | Methods and compositions for treating schizophrenia |
| US10159648B2 (en) | 2015-05-22 | 2018-12-25 | Agenebio, Inc. | Extended release pharmaceutical compositions of levetiracetam |
| EP3461819A1 (en) | 2017-09-29 | 2019-04-03 | Probiodrug AG | Inhibitors of glutaminyl cyclase |
| US10806717B2 (en) | 2013-03-15 | 2020-10-20 | The Johns Hopkins University | Methods and compositions for improving cognitive function |
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| TW200501962A (en) * | 2003-04-01 | 2005-01-16 | Novartis Ag | Use of carbamazepine derivatives for the treatment of agitation in dementia patients |
| CA2551486A1 (en) * | 2003-12-22 | 2006-06-22 | Abbott Laboratories | Fused bicycloheterocycle substituted quinuclidine derivatives |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0515301A2 (en) * | 1991-05-14 | 1992-11-25 | Ernir Snorrason | Improvements in benzodiazepine treatment by cholinesterterase inhibitors |
| EP0879596A2 (en) * | 1991-05-14 | 1998-11-25 | Ernir Snorasson | Use of cholinesterase inhibitors to reduce benzodiazepine side effects |
| WO1999007378A1 (en) * | 1997-08-11 | 1999-02-18 | THE UNIVERSITY OF SOUTH FLORIDA A Corporation of the State of Florida | Nicotine antagonists for nicotine-responsive neuropsychiatric disorders |
| WO1999052519A2 (en) * | 1998-04-14 | 1999-10-21 | The General Hospital Corporation | Methods for treating neuropsychiatric disorders |
-
1999
- 1999-10-12 EE EEP200100136A patent/EE200100136A/en unknown
- 1999-10-12 CA CA002345767A patent/CA2345767A1/en not_active Abandoned
- 1999-10-12 SK SK459-2001A patent/SK4592001A3/en unknown
- 1999-10-12 WO PCT/EP1999/007804 patent/WO2000023057A2/en not_active Application Discontinuation
- 1999-10-12 BR BR9914419-0A patent/BR9914419A/en not_active IP Right Cessation
- 1999-10-12 HU HU0103781A patent/HUP0103781A3/en unknown
- 1999-10-12 EP EP99952580A patent/EP1121131A2/en not_active Withdrawn
- 1999-10-12 PL PL99348107A patent/PL348107A1/en unknown
- 1999-10-12 CN CN99812184A patent/CN1367697A/en active Pending
- 1999-10-12 KR KR1020017002286A patent/KR20010072878A/en not_active Application Discontinuation
- 1999-10-12 JP JP2000576832A patent/JP2002527469A/en not_active Withdrawn
- 1999-10-12 ID IDW20010828A patent/ID28441A/en unknown
- 1999-10-12 IL IL14258899A patent/IL142588A0/en unknown
- 1999-10-12 TR TR2001/01082T patent/TR200101082T2/en unknown
- 1999-10-12 AU AU64727/99A patent/AU6472799A/en not_active Abandoned
-
2001
- 2001-03-01 BG BG105302A patent/BG105302A/en unknown
- 2001-03-20 NO NO20011403A patent/NO20011403L/en not_active Application Discontinuation
- 2001-04-10 HR HR20010262A patent/HRP20010262A2/en not_active Application Discontinuation
- 2001-04-12 ZA ZA200103081A patent/ZA200103081B/en unknown
-
2002
- 2002-01-10 HK HK02100158.6A patent/HK1039745A1/en unknown
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0515301A2 (en) * | 1991-05-14 | 1992-11-25 | Ernir Snorrason | Improvements in benzodiazepine treatment by cholinesterterase inhibitors |
| EP0879596A2 (en) * | 1991-05-14 | 1998-11-25 | Ernir Snorasson | Use of cholinesterase inhibitors to reduce benzodiazepine side effects |
| WO1999007378A1 (en) * | 1997-08-11 | 1999-02-18 | THE UNIVERSITY OF SOUTH FLORIDA A Corporation of the State of Florida | Nicotine antagonists for nicotine-responsive neuropsychiatric disorders |
| WO1999052519A2 (en) * | 1998-04-14 | 1999-10-21 | The General Hospital Corporation | Methods for treating neuropsychiatric disorders |
Non-Patent Citations (9)
| Title |
|---|
| FERNANDEZ H.H. ET AL: "Donepezil for Huntington's disease." MOVEMENT DISORDERS, (2000) 15/1 (173-176). , XP000892632 * |
| GALASKO D: "A CLINICAL APPROACH TO DEMENTIA WITH LEWY BODIES" THE NEUROLOGIST, vol. 5, no. 5, September 1999 (1999-09), pages 247-257, XP000878694 * |
| GEIZER M. ET AL: "Combination of risperidone and donepezil in Lewy body dementia" CAN. J. PSYCHIATRY,May 1998 (1998-05), pages 421-422, XP000892680 * |
| KELLY J S: "Alzheimer's disease: the tacrine legacy" TRENDS IN PHARMACOLOGICAL SCIENCES,GB,ELSEVIER TRENDS JOURNAL, CAMBRIDGE, vol. 20, no. 4, April 1999 (1999-04), pages 127-129, XP004172560 ISSN: 0165-6147 * |
| MAGNUSON T M ET AL: "Extrapyramidal side effects in a patient treated with risperidone plus donepezil ÄletterÜ." AMERICAN JOURNAL OF PSYCHIATRY, (1998 OCT) 155 (10) 1458-9. , XP000892634 * |
| MAZUREK A. A.: "Treatment of Alzheimer's disease" N ENG J. MED, vol. 342, no. 11, 16 March 2000 (2000-03-16), pages 821-822, XP000901026 * |
| MELTZER, H. Y. (1) ET AL: "Atypical antipsychotic drugs (APD) but not typical APD increased extracellular acetylcholine (ACh-ext) levels in rat medial prefrontal cortex (mPFC) in the absence AChEsterase (AChE) inhibition." SOCIETY FOR NEUROSCIENCE ABSTRACTS, (1999) VOL. 25, NO. 1-2, PP. 452. MEETING INFO.: 29TH ANNUAL MEETING OF THE SOCIETY FOR NEUROSCIENCE, PART 1 MIAMI BEACH, FLORIDA, USA OCTOBER 23-28, 1999 THE SOCIETY FOR NEUROSCIENCE. , XP000892699 * |
| SIMONSON W.: "Promising agents for treating Alzheimer's disease." AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY, (1 NOV 1998) 55/21 SUPPL. (S11-S16). , XP002134583 * |
| YAQUB B.A.: "New horizons in management of Alzheimer 's disease." SAUDI MEDICAL JOURNAL, (1999) 20/9 (671-677). , XP000892838 * |
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| AU2002231766B2 (en) * | 2001-02-05 | 2005-12-22 | Novartis Ag | New use of iloperidone |
| AU2006201188B2 (en) * | 2001-02-05 | 2007-11-15 | Novartis Ag | New use of iloperidone |
| JP2005508975A (en) * | 2001-10-30 | 2005-04-07 | ノバルティス アクチエンゲゼルシャフト | Depot formulation of iloperidone and star polymer |
| US8815293B2 (en) | 2001-10-30 | 2014-08-26 | Novartis Ag | Organic compounds |
| US7767230B2 (en) | 2001-10-30 | 2010-08-03 | Novartis Ag | Organic compounds |
| US8227488B2 (en) | 2002-07-15 | 2012-07-24 | Novartis Ag | Injectable depot formulation comprising crystals of iloperidone |
| US8614232B2 (en) | 2002-07-15 | 2013-12-24 | Novartis Ag | Injectable depot formulation comprising crystals of iloperidone |
| US8293765B2 (en) | 2002-07-15 | 2012-10-23 | Novartis Ag | Injectable depot formulation comprising crystals of iloperidone |
| WO2004084905A3 (en) * | 2003-03-24 | 2005-04-28 | Univ Florida | Use of 5-ht2c receptor activity affecting compounds for treating idiopathic hyperhidrosis and associated conditions |
| WO2004084905A2 (en) * | 2003-03-24 | 2004-10-07 | University Of Florida | Use of 5-ht2c receptor activity affecting compounds for treating idiopathic hyperhidrosis and associated conditions |
| WO2005065645A2 (en) * | 2003-12-31 | 2005-07-21 | Actavis Group Hf | Donepezil formulations |
| WO2005065645A3 (en) * | 2003-12-31 | 2005-10-27 | Alpharma Inc | Donepezil formulations |
| WO2008055945A1 (en) | 2006-11-09 | 2008-05-15 | Probiodrug Ag | 3-hydr0xy-1,5-dihydr0-pyrr0l-2-one derivatives as inhibitors of glutaminyl cyclase for the treatment of ulcer, cancer and other diseases |
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| EP2481408A2 (en) | 2007-03-01 | 2012-08-01 | Probiodrug AG | New use of glutaminyl cyclase inhibitors |
| WO2008104580A1 (en) | 2007-03-01 | 2008-09-04 | Probiodrug Ag | New use of glutaminyl cyclase inhibitors |
| EP2865670A1 (en) | 2007-04-18 | 2015-04-29 | Probiodrug AG | Thiourea derivatives as glutaminyl cyclase inhibitors |
| WO2009011560A1 (en) * | 2007-07-16 | 2009-01-22 | Espinosa Abdala Leopoldo De Je | Pharmaceutical composition combining risperidone and donepezil, and use thereof for treating psychotic disorders such as schizophrenia and dimentias such as alzheimer's disease |
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| WO2011110613A1 (en) | 2010-03-10 | 2011-09-15 | Probiodrug Ag | Heterocyclic inhibitors of glutaminyl cyclase (qc, ec 2.3.2.5) |
| WO2011131748A2 (en) | 2010-04-21 | 2011-10-27 | Probiodrug Ag | Novel inhibitors |
| WO2012123563A1 (en) | 2011-03-16 | 2012-09-20 | Probiodrug Ag | Benz imidazole derivatives as inhibitors of glutaminyl cyclase |
| US10624875B2 (en) | 2012-11-14 | 2020-04-21 | The Johns Hopkins University | Methods and compositions for treating schizophrenia |
| US10154988B2 (en) | 2012-11-14 | 2018-12-18 | The Johns Hopkins University | Methods and compositions for treating schizophrenia |
| WO2014144801A1 (en) | 2013-03-15 | 2014-09-18 | Agenebio Inc. | Methods and compositions for improving cognitive function |
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Also Published As
| Publication number | Publication date |
|---|---|
| EP1121131A2 (en) | 2001-08-08 |
| ZA200103081B (en) | 2002-07-12 |
| PL348107A1 (en) | 2002-05-06 |
| HRP20010262A2 (en) | 2002-06-30 |
| ID28441A (en) | 2001-05-24 |
| BR9914419A (en) | 2001-06-26 |
| SK4592001A3 (en) | 2001-12-03 |
| CN1367697A (en) | 2002-09-04 |
| HK1039745A1 (en) | 2002-05-10 |
| HUP0103781A3 (en) | 2003-09-29 |
| HUP0103781A2 (en) | 2002-03-28 |
| NO20011403D0 (en) | 2001-03-20 |
| KR20010072878A (en) | 2001-07-31 |
| CA2345767A1 (en) | 2000-04-27 |
| BG105302A (en) | 2001-11-30 |
| NO20011403L (en) | 2001-03-20 |
| WO2000023057A3 (en) | 2000-07-27 |
| AU6472799A (en) | 2000-05-08 |
| TR200101082T2 (en) | 2001-09-21 |
| JP2002527469A (en) | 2002-08-27 |
| EE200100136A (en) | 2002-06-17 |
| IL142588A0 (en) | 2002-03-10 |
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