WO1995019164A1 - Use of m3 muscarinic antagonists for the treatment of motion sickness - Google Patents
Use of m3 muscarinic antagonists for the treatment of motion sickness Download PDFInfo
- Publication number
- WO1995019164A1 WO1995019164A1 PCT/EP1995/000044 EP9500044W WO9519164A1 WO 1995019164 A1 WO1995019164 A1 WO 1995019164A1 EP 9500044 W EP9500044 W EP 9500044W WO 9519164 A1 WO9519164 A1 WO 9519164A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- motion sickness
- treatment
- muscarinic receptor
- selective
- muscarinic antagonists
- Prior art date
Links
- 201000003152 motion sickness Diseases 0.000 title claims abstract description 18
- 229940121948 Muscarinic receptor antagonist Drugs 0.000 title claims abstract description 15
- 239000003149 muscarinic antagonist Substances 0.000 title claims description 10
- HXGBXQDTNZMWGS-RUZDIDTESA-N darifenacin Chemical compound C=1C=CC=CC=1C([C@H]1CN(CCC=2C=C3CCOC3=CC=2)CC1)(C(=O)N)C1=CC=CC=C1 HXGBXQDTNZMWGS-RUZDIDTESA-N 0.000 claims abstract description 9
- 150000003839 salts Chemical class 0.000 claims description 8
- 238000000034 method Methods 0.000 claims description 5
- 230000002265 prevention Effects 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 239000005557 antagonist Substances 0.000 claims 2
- 229960002677 darifenacin Drugs 0.000 abstract description 2
- 150000001875 compounds Chemical class 0.000 description 16
- STECJAGHUSJQJN-GAUPFVANSA-N Hyoscine Natural products C1([C@H](CO)C(=O)OC2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-GAUPFVANSA-N 0.000 description 8
- STECJAGHUSJQJN-UHFFFAOYSA-N N-Methyl-scopolamin Natural products C1C(C2C3O2)N(C)C3CC1OC(=O)C(CO)C1=CC=CC=C1 STECJAGHUSJQJN-UHFFFAOYSA-N 0.000 description 8
- STECJAGHUSJQJN-FWXGHANASA-N scopolamine Chemical compound C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-FWXGHANASA-N 0.000 description 8
- 229960002646 scopolamine Drugs 0.000 description 8
- 229930000680 A04AD01 - Scopolamine Natural products 0.000 description 7
- 230000000694 effects Effects 0.000 description 4
- 238000007796 conventional method Methods 0.000 description 3
- 230000004886 head movement Effects 0.000 description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 2
- 102000014415 Muscarinic acetylcholine receptor Human genes 0.000 description 2
- 108050003473 Muscarinic acetylcholine receptor Proteins 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000003551 muscarinic effect Effects 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 210000002460 smooth muscle Anatomy 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- RGHNJXZEOKUKBD-SQOUGZDYSA-M D-gluconate Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@@H](O)C([O-])=O RGHNJXZEOKUKBD-SQOUGZDYSA-M 0.000 description 1
- 208000012258 Diverticular disease Diseases 0.000 description 1
- 206010013554 Diverticulum Diseases 0.000 description 1
- 239000004150 EU approved colour Substances 0.000 description 1
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 1
- 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 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- JVTAAEKCZFNVCJ-UHFFFAOYSA-M Lactate Chemical compound CC(O)C([O-])=O JVTAAEKCZFNVCJ-UHFFFAOYSA-M 0.000 description 1
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 1
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 1
- 206010028813 Nausea Diseases 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-L Phosphate ion(2-) Chemical compound OP([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-L 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 description 1
- 206010046543 Urinary incontinence Diseases 0.000 description 1
- 206010047700 Vomiting Diseases 0.000 description 1
- OIPILFWXSMYKGL-UHFFFAOYSA-N acetylcholine Chemical compound CC(=O)OCC[N+](C)(C)C OIPILFWXSMYKGL-UHFFFAOYSA-N 0.000 description 1
- 229960004373 acetylcholine Drugs 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 229930013930 alkaloid Natural products 0.000 description 1
- 150000003797 alkaloid derivatives Chemical class 0.000 description 1
- 230000003466 anti-cipated effect Effects 0.000 description 1
- 230000001387 anti-histamine Effects 0.000 description 1
- 239000000739 antihistaminic agent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-M bisulphate group Chemical group S([O-])(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-M 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 230000008499 blood brain barrier function Effects 0.000 description 1
- 210000001218 blood-brain barrier Anatomy 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 239000002775 capsule Substances 0.000 description 1
- 230000000747 cardiac effect Effects 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000019771 cognition Effects 0.000 description 1
- 230000002860 competitive effect Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 206010013781 dry mouth Diseases 0.000 description 1
- 201000011191 dyskinesia of esophagus Diseases 0.000 description 1
- 239000000796 flavoring agent Substances 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 229940050410 gluconate Drugs 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 239000003112 inhibitor Substances 0.000 description 1
- 238000002347 injection Methods 0.000 description 1
- 239000007924 injection Substances 0.000 description 1
- 208000002551 irritable bowel syndrome Diseases 0.000 description 1
- 239000008101 lactose Substances 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000004899 motility Effects 0.000 description 1
- 210000004165 myocardium Anatomy 0.000 description 1
- 230000008693 nausea Effects 0.000 description 1
- 229940006093 opthalmologic coloring agent diagnostic Drugs 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 230000035479 physiological effects, processes and functions Effects 0.000 description 1
- 239000000902 placebo Substances 0.000 description 1
- 229940068196 placebo Drugs 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 229910021653 sulphate ion Inorganic materials 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 150000003892 tartrate salts Chemical class 0.000 description 1
- 238000005303 weighing 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
-
- 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
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
Definitions
- This invention relates to treatment of motion sickness, a condition characterised by nausea and vomiting caused by body motion. Seasickness and airsickness and spacesickness are instances of this condition.
- Motion sickness is commonly prevented by oral or transdermal administration of the alkaloid scopolamine (hyoscine) which is a known antimuscarinic agent, that is an agent which is a competitive inhibitor of acetylcholine at muscarinic receptor sites.
- scopolamine is not selective between the three types of muscarinic receptor sites, known respectively as the M lf M 2 and M 3 sites and therefore the receptor subtype involved in the control of motion sickness is unknown.
- scopolamine has undesirable side effects such as dry mouth, adverse effects on cognition and certain cardiac effects.
- muscarinic receptor antagonists which are selective for M 3 muscarinic sites over the Mi and M 2 sites, that is they are selective for smooth muscle muscarinic sites over cardiac muscle sites. They are gut-selective, generally have little or no antihistamine activity and include compounds which are useful in the treatment of diseases associated with altered motility and/or tone of smooth muscle, including irritable bowel syndrome, diverticular disease, urinary incontinence, oesophageal dysmotility and chronic obstructive airways disease.
- M 3 selective muscarinic receptor antagonists are effective in preventing or alleviating motion sickness without at least some of the side effects associated with known motion sickness remedies such as scopolamine.
- One aspect of the invention comprises a M 3 selective muscarinic receptor antagonist for use in the treatment or prevention of motion sickness.
- the invention also relates to a method of treating or preventing motion sickness which comprises administering to a patient an effective amount of a M 3 selective muscarinic receptor antagonist.
- the invention also relates to use of an M 3 -selective muscarinic receptor antagonist for the manufacture of a medicament for treatment or prevention of motion sickness.
- the compounds preferred for this purpose are those having lipophilic rather than polar physicochemical characteristics.
- Particularly preferred compounds are UK-88525 mentioned above, and its pharmaceutically acceptable salts. Preparation of UK-88525 is described in European Patent 388054.
- the pharmaceutically acceptable salts of this compound include acid addition salts such as the hydrochloride, hydrobromide, sulphate and bisulphate, phosphate or hydrogen phosphate, acetate, besylate, citrate, fumarate, gluconate, lactate, maleate, mesylate, succinate and tartrate salts. These salts may be prepared by conventional methods.
- the M 3 selective muscarinic receptor antagonist compound may generally be administered to a patient by conventional methods, for example orally or by injection, as described in the above-mentioned patent publications.
- the compounds may be made up into the appropriate formulations for administration by conventional methods.
- they may be administered orally in the form of tablets containing excipients such as starch or lactose, or in capsules or ovules either alone or in admixture with excipients, or in the form of elixirs or suspensions containing flavouring or colouring agents.
- They may be injected parenterally, for example intravenously, intramuscularly or subcutaneously.
- a sterile aqueous solution which may contain other substances, for example salts or glucose to make the solution isotonic with blood.
- the dose of active compound and frequency of administration required will generally depend not only on the identity of the compound but on the physiology of the patient.
- the dose administered will generally be determined by a physician bearing in mind the age, weight, anticipated response and medical history of the patient.
- the dose administered is likely to be from 1 to lOOmg.
- the action of the M 3 -selective muscarinic receptor antagonists in preventing or alleviating motion sickness may be demonstrated as follows.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| AU14553/95A AU1455395A (en) | 1994-01-14 | 1995-01-04 | Use of m3 muscarinic antagonists for the treatment of motion sickness |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB9400600A GB9400600D0 (en) | 1994-01-14 | 1994-01-14 | Treatment of motion seckness |
| GB9400600.4 | 1994-01-14 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO1995019164A1 true WO1995019164A1 (en) | 1995-07-20 |
Family
ID=10748758
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/EP1995/000044 WO1995019164A1 (en) | 1994-01-14 | 1995-01-04 | Use of m3 muscarinic antagonists for the treatment of motion sickness |
Country Status (6)
| Country | Link |
|---|---|
| AU (1) | AU1455395A (enrdf_load_html_response) |
| GB (1) | GB9400600D0 (enrdf_load_html_response) |
| IL (1) | IL112257A0 (enrdf_load_html_response) |
| TW (1) | TW276995B (enrdf_load_html_response) |
| WO (1) | WO1995019164A1 (enrdf_load_html_response) |
| ZA (1) | ZA95244B (enrdf_load_html_response) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997009980A1 (en) * | 1995-09-15 | 1997-03-20 | Pfizer Research And Development Company, N.V./S.A. | Pharmaceutical formulations containing darifenacin |
| EP0813870A1 (en) * | 1996-06-18 | 1997-12-29 | Pfizer Limited | Use of darifenacin to enhance cognitive functions |
| WO2003080599A1 (en) | 2002-03-26 | 2003-10-02 | Novartis International Pharmaceutical Ltd. | Stable hydrate of a muscarinic receptor antagonist |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0350309A1 (en) * | 1988-07-08 | 1990-01-10 | Pfizer Limited | Piperidine derivatives |
| EP0388054A1 (en) * | 1989-03-17 | 1990-09-19 | Pfizer Limited | Pyrrolidine derivatives |
| WO1991017973A1 (en) * | 1990-05-18 | 1991-11-28 | Merrell Dow Pharmaceuticals Inc. | 5H-DIBENZO(a,d)CYCLOHEPTENES AS MUSCARINIC RECEPTOR ANTAGONISTS |
| GB2260323A (en) * | 1991-10-11 | 1993-04-14 | British Tech Group | 4-piperidinyl diphenylacetates |
-
1994
- 1994-01-14 GB GB9400600A patent/GB9400600D0/en active Pending
- 1994-12-06 TW TW083111324A patent/TW276995B/zh active
-
1995
- 1995-01-04 AU AU14553/95A patent/AU1455395A/en not_active Abandoned
- 1995-01-04 WO PCT/EP1995/000044 patent/WO1995019164A1/en active Application Filing
- 1995-01-05 IL IL11225795A patent/IL112257A0/xx unknown
- 1995-01-13 ZA ZA95244A patent/ZA95244B/xx unknown
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0350309A1 (en) * | 1988-07-08 | 1990-01-10 | Pfizer Limited | Piperidine derivatives |
| EP0388054A1 (en) * | 1989-03-17 | 1990-09-19 | Pfizer Limited | Pyrrolidine derivatives |
| WO1991017973A1 (en) * | 1990-05-18 | 1991-11-28 | Merrell Dow Pharmaceuticals Inc. | 5H-DIBENZO(a,d)CYCLOHEPTENES AS MUSCARINIC RECEPTOR ANTAGONISTS |
| GB2260323A (en) * | 1991-10-11 | 1993-04-14 | British Tech Group | 4-piperidinyl diphenylacetates |
Non-Patent Citations (3)
| Title |
|---|
| "Idaverine, an M2- vs M3- selective muscarin antagonist does not prevent motion sickness in cats", PHARMACOL.BIOCHEM.BEHAV., vol. 40, no. 2, pages 345 - 9 * |
| "The effect of a selective muscarinic receptor antagonist and scopolamine on motion sickness, skin conductance and heart rate in humans", SCIENTIFIC MEETING OF THE PHYSIOLOGICAL SOCIETY, BRISTOL, UK, FEBRUARY 10-11, 1994. J PHYSIOLOGY, vol. 476P, no. 0, pages 47p. * |
| AVIATION SPACE ENVIRON.MED., vol. 59, no. 1, pages 63 - 6 * |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997009980A1 (en) * | 1995-09-15 | 1997-03-20 | Pfizer Research And Development Company, N.V./S.A. | Pharmaceutical formulations containing darifenacin |
| US6106864A (en) * | 1995-09-15 | 2000-08-22 | Pfizer Inc. | Pharmaceutical formulations containing darifenacin |
| EP1245231A3 (en) * | 1995-09-15 | 2003-01-15 | Pfizer Research and Development Company, N.V./S.A. | Pharmaceutical formulations containing darifenacin |
| EP0813870A1 (en) * | 1996-06-18 | 1997-12-29 | Pfizer Limited | Use of darifenacin to enhance cognitive functions |
| WO2003080599A1 (en) | 2002-03-26 | 2003-10-02 | Novartis International Pharmaceutical Ltd. | Stable hydrate of a muscarinic receptor antagonist |
| CN100345840C (zh) * | 2002-03-26 | 2007-10-31 | 诺瓦提斯国际药物有限公司 | 毒蕈碱性受体拮抗剂的稳定水合物 |
| US7696357B2 (en) | 2002-03-26 | 2010-04-13 | Novartis International Pharmaceutical Ltd. | Stable hydrate of a muscarinic receptor antagonist |
| KR101026283B1 (ko) * | 2002-03-26 | 2011-03-31 | 노파르티스 인터내셔널 파마슈티칼 리미티드 | 무스카린 수용체 안타고니스트의 안정한 수화물 |
| EP2336124A1 (en) * | 2002-03-26 | 2011-06-22 | Novartis International Pharmaceutical Ltd. | Stable hydrate of a muscarinic receptor antagonist |
Also Published As
| Publication number | Publication date |
|---|---|
| GB9400600D0 (en) | 1994-03-09 |
| IL112257A0 (en) | 1995-03-30 |
| ZA95244B (en) | 1996-07-15 |
| TW276995B (enrdf_load_html_response) | 1996-06-01 |
| AU1455395A (en) | 1995-08-01 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Gristwood et al. | Levobupivacaine: a new safer long acting local anaesthetic agent | |
| JP3823194B2 (ja) | ５ｈｔ▲３▼拮抗剤の新規医薬用途 | |
| AU740504B2 (en) | Use of descarboethoxyloratadine for the manufacture of a medicament for the treatment of urinary incontinence, motion sickness and vertigo | |
| BG63190B1 (bg) | Използване на оптически чист (+) норцисаприд за лечение на емезис и смущения на централната нервна система | |
| WO2000025821A1 (en) | Method of treating and diagnosing restless legs syndrome and corresponding means | |
| AU764304B2 (en) | Use of saredutant and of its pharmaceutically acceptable salts for the preparation of medicinal products that are useful in the treatment or prevention of major depressive disorders | |
| HK1046641B (en) | Orally disintegrating composition comprising mirtazapine | |
| WO1995019164A1 (en) | Use of m3 muscarinic antagonists for the treatment of motion sickness | |
| MX2013013125A (es) | Combinaciones de solifenacina y estimulantes salivales para el tratamiento de la vejiga hiperactiva. | |
| AU7490096A (en) | Treatment of traumatic brain injury | |
| EP0846465B1 (en) | Nicorandil against anxiety neurosis | |
| US6110927A (en) | Loratadine for use as an antiarrhythmic | |
| US20060269597A1 (en) | Tannate Compositions and Methods of Use for the Treatment of Respiratory Tract Conditions | |
| Diemont et al. | Low-dose isradipine once daily effectively controls 24-h blood pressure in essential hypertension | |
| KR930001105B1 (ko) | 심부정맥 예방 또는 치료용약제 | |
| US10369157B1 (en) | Multi-agent formulation | |
| EP1155693A1 (en) | Intermittent claudication remedies | |
| AU2001264806A1 (en) | Stable liquid and solid formulations | |
| EP1223939A1 (en) | Method of treating weight gain | |
| US20040248927A1 (en) | Preventive agent/remedial agent for constipation predominant ibs | |
| Man in’t Veld | The place of isradipine in the treatment of hypertension | |
| AU762060B2 (en) | Use of descarboethoxyloratadine for the manufacture of a medicament for the treatment of vertigo | |
| JP2003512328A5 (enrdf_load_html_response) | ||
| MXPA99007802A (es) | Uso de descarboetociloratadina para la preparacion de un farmaco para el tratamiento de la incontinencia urinaria, malestar causado por el movimiento y vertigo | |
| JP2000212091A (ja) | 消化管機能異常治療剤 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| AK | Designated states |
Kind code of ref document: A1 Designated state(s): AU CA CN FI JP KR MX NO NZ US |
|
| AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): AT BE CH DE DK ES FR GB GR IE IT LU MC NL PT SE |
|
| DFPE | Request for preliminary examination filed prior to expiration of 19th month from priority date (pct application filed before 20040101) | ||
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
| 122 | Ep: pct application non-entry in european phase | ||
| NENP | Non-entry into the national phase |
Ref country code: CA |