WO1996011680A2 - Use of gaba agonists in the treatment of emesis - Google Patents
Use of gaba agonists in the treatment of emesis Download PDFInfo
- Publication number
- WO1996011680A2 WO1996011680A2 PCT/EP1995/004025 EP9504025W WO9611680A2 WO 1996011680 A2 WO1996011680 A2 WO 1996011680A2 EP 9504025 W EP9504025 W EP 9504025W WO 9611680 A2 WO9611680 A2 WO 9611680A2
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- emesis
- gaba
- acid
- use according
- induced
- Prior art date
Links
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
- A61K31/66—Phosphorus compounds
- A61K31/662—Phosphorus acids or esters thereof having P—C bonds, e.g. foscarnet, trichlorfon
-
- 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
- A61K31/137—Arylalkylamines, e.g. amphetamine, epinephrine, salbutamol, ephedrine or methadone
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
-
- 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
- A61K31/185—Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids
- A61K31/19—Carboxylic acids, e.g. valproic acid
- A61K31/195—Carboxylic acids, e.g. valproic acid having an amino group
- A61K31/197—Carboxylic acids, e.g. valproic acid having an amino group the amino and the carboxyl groups being attached to the same acyclic carbon chain, e.g. gamma-aminobutyric acid [GABA], beta-alanine, epsilon-aminocaproic acid, pantothenic acid
Definitions
- the present invention relates to the use of ⁇ -aminobutyric acid (GABA) agonists having an agonist action at GABA B receptors in the treatment of emesis.
- GABA ⁇ -aminobutyric acid
- GABA is an endogenous inhibitory neu retransmitter in the CNS and peripheral nervous systems.
- Receptors for GABA have been divided into GABA and GABA ⁇ receptor sub-types.
- GABAB agonists are described as being of use in the treatment of CNS disorders, such as muscle relaxation in spinal spasticity, cardiovascular disorders, asthma, gut motility disorders such as irritable bowel syndrome and as prokinetic and anti-tussive agents.
- the invention accordingly provides, in a first aspect, the novel use of a GABA agonist having an agonist action at GABA B receptors, selected from the compounds ⁇ -phenyl- ⁇ -aminobutyric acid ( ⁇ -phenyl-GABA), 3-amino-2-(4- chorophenyl)-nitropropane, 1-(aminomethyl)cyclohexaneacetic acid
- a GABA agonist having an agonist action at GABA B receptors, selected from the compounds ⁇ -phenyl- ⁇ -aminobutyric acid ( ⁇ -phenyl-GABA), 3-amino-2-(4- chorophenyl)-nitropropane, 1-(aminomethyl)cyclohexaneacetic acid
- Patent Specification No. 2185483 such as D-N-(2-pyrrolidone-5-carbonyl)- piperidine, in the treatment of emesis.
- GABA agonists having an agonist action at GABA B receptors listed above and gene ⁇ cally and specifically disclosed in the above referenced patent specifications in the preparation of a medicament for use in the treatment of emesis.
- a method for the treatment of a mammal including man, suffering from or susceptible to emesis, comprising administration of an effective amount of a GABA agonist having an agonist action at GABA B receptors listed above or generically or specifically disclosed in the above referenced patent specifications.
- baclofen reduced the frequency of vomiting due to duodenal ileus in a patient with Duchenne muscular dystrophy.
- ( ⁇ ) baclofen in the treatment of emesis caused by duodenal ileus is not included within the scope of the instant invention.
- GABA agonists having an agonist action at GABA B receptors have been shown to have anti-emetic activity as indicated by for example their ability to inhibit emesis induced by a variety of emetogens in the ferret.
- emesis The treatment of emesis mentioned hereinbefore includes the treatment of nausea, retching and vomiting.
- Emesis includes acute emesis, delayed or late emesis and anticipatory emesis.
- GABA agonists having an agonist action at GABA B receptors are useful in the treatment of emesis however induced.
- emesis may be induced by drugs such as cancer chemotherapeutic agents such as alkylating agents, e.g. cyclop hosp ham id e, carmustine, lomustine and chlorambucil; cytotoxic antibiotics, e.g. dactinomycin, doxorubicin, mitomycin-C and bleomycin; anti-metabolites, e.g.
- cytarabine methotrexate and 5-fluorouracil
- vinca alkaloids e.g. etoposide, vinblastine and vincristine
- others such as cisplatin, dacarbazine, procarbazine and hydroxyurea; and combinations thereof
- radiation sickness e.g. irradiation of the thorax or abdomen, such as in the treatment of cancer; poisons; toxins such as toxins caused by metabolic disorders or by infection, e.g.
- gastritis or released during bacterial or viral gastrointestinal infection; pregnancy; vestibular disorders, such as motion sickness, vertigo, dizziness and Meniere's disease; post-operative sickness; gastrointestinal obstruction; reduced gastrointestinal motility; visceral pain, e.g. myocardial infarction or peritonitis; migraine; increased intercranial pressure; decreased intercranial pressure (e.g.
- altitude sickness such as morphine
- opioid analgesics such as morphine
- gastro-oesophageal reflux disease acid indigestion, over-indulgence of food or drink, acid stomach, sour stomach, waterbrash/regurgitation
- heartburn such as episodic heartburn, nocturnal heartburn, and meal-induced heartburn and dyspepsia.
- GABA B agonists may be administered as the raw chemical but are preferably presented as a pharmaceutical formulation. Suitable pharmaceutical formulations for GABA B agonists are described in the art, for example as in the above referenced patent specifications.
- GABA B agonists may be formulated for oral, buccal, parenteral, depot or rectal administration or in a form suitable for administration by inhalation or insufflation (either through the mouth or nose). Oral and parenteral formulations are preferred.
- the pharmaceutical compositions may take the form of, for example, tablets or capsules prepared by conventional means with pharmaceutically acceptable excipients such as binding agents (e.g. pregelatinised maize starch, polyvinylpyrrolidone or hydroxypropyl methylcellulose); fillers (e.g. lactose, microcrystaliine cellulose or calcium hydrogen phosphate); lubricants (e.g. magnesium stearate, talc or silica); disintegrants (e.g. potato starch or sodium starch glycollate); or wetting agents (e.g. sodium lauryl sulphate).
- binding agents e.g. pregelatinised maize starch, polyvinylpyrrolidone or hydroxypropyl methylcellulose
- fillers e.g. lactose, microcrystaliine cellulose or calcium hydrogen phosphate
- lubricants e.g. magnesium stearate, talc or silica
- disintegrants e.g. potato starch
- Liquid preparations for oral administration may take the form of, for example, solutions, syrups or suspensions, or they may be presented as a dry product for constitution with water or other suitable vehicle before use.
- Such liquid preparations may be prepared by conventional means with pharmaceutically acceptable additives such as suspending agents (e.g. sorbitol syrup, cellulose derivatives or hydrogenated edible fats); emulsifying agents (e.g. lecithin or acacia); non-aqueous vehicles (e.g. almond oil, oily esters, ethyl alcohol or fractionated vegetable oils); and preservatives (e.g. methyl or propyl- p_-hydroxybenzoates or sorbic acid).
- the preparations may also contain buffer salts, flavouring, colouring and sweetening agents as appropriate.
- Preparations for oral administration may be suitably formulated to give controlled release of the active compound.
- composition may take the form of tablets or lozenges formulated in conventional manner.
- the GABA B agonists may be formulated for parenteral administration by bolus injection or continuous infusion.
- Formulations for injection may be presented in unit dosage form e.g. in ampoules or in multi-dose containers, with an added preservative.
- the compositions may take such forms as suspensions, solutions or emulsions in oily or aqueous vehicles, and may contain formulatory agents such as suspending, stabilising and/or dispersing agents.
- the active ingredient may be in powder form for constitution with a suitable vehicle, e.g. sterile pyrogen-free water, before use.
- the GABA B agonists may also be formulated in rectal compositions such as suppositories or retention enemas, e.g. containing conventional suppository bases such as cocoa butter or other glycerides.
- the GABA B agonists may also be formulated as depot preparations. Such long acting formulations may be administered by implantation (for example subcutaneously or intramuscularly) or by intramuscular injection.
- the compounds of the invention may be formulated with suitable polymeric or hydrophobic materials (for example as an emulsion in an acceptable oil) or ion exchange resins, or as sparingly soluble derivatives, for example, as a sparingly soluble salt.
- the GABA B agonists may be formulated as solutions for administration via a suitable metered or unit dose device or alternatively as a powder mix with a suitable carrier for administration using a suitable delivery device.
- Suitable dose ranges are described in the art, that is to say that for use as anti- emetics the compounds may be used at doses appropriate for other conditions for which GABA B agonists are known to be useful. It will be appreciated that it may be necessary to make routine variations to the dosage, depending on the age and condition of the patient, and the precise dosage will be ultimately at the discretion of the attendant physician or veterinarian. The dosage will also depend on the route of administration and the particular compound selected.
- a suitable dose range is for example 0.1 mg/kg to about 200 mg/kg, e.g. 0.1 mg/kg to 10 mg kg, bodyweight per day.
- GABA B agonists having an agonist action at GABA B receptors useful in the instant invention may, if desired, be administered in combination with one or more other therapeutic agents and formulated for administration by any convenient route in a conventional manner. Appropriate doses will be readily appreciated by those skilled in the art.
- GABA agonists having an agonist action at GABA B receptors may be administered in combination with a systemic anti-inflammatory corticosteroid such as methyl prednisolone or dexamethasone, a 5HT3 antagonist such as ondansetron, granisetron or metoclopramide, or a tachykinin antagonist, including substance P antagonists and other neurokinin antagonists, such as an NK-* receptor antagonist, or a sympathomimetic such as ephedrine, pseudoephedrine or oxymetazoline.
- a systemic anti-inflammatory corticosteroid such as methyl prednisolone or dexamethasone
- a 5HT3 antagonist such as ondansetron, granisetron or metoclopramide
- a tachykinin antagonist including substance P antagonists and other neurokinin antagonists, such as an NK-* receptor antagonist, or a sympathomimetic such as ephedrine, pseudo
- the anti-emetic activity of the GABA B agonist ( ⁇ ) baclofen was demonstrated by its ability to inhibit emesis induced by radiation, cisplatin, morphine and ipecacuanha in the ferret.
- the anti-emetic activity of R(-) baclofen (active isomer) was demonstrated by its ability to inhibit radiation-induced emesis in the ferret.
- Cisplatin Test In this model of emesis the onset of retching and vomiting occurs approximately 1 hour after the administration of cisplatin (200mg/m 2 i.p.). The test compound was administered (s.c.) 1 hour after the administration of the emetogen and its effect on emesis determined by comparison with appropriate controls (e.g. water).
Abstract
Description
Claims
Priority Applications (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
AU37458/95A AU3745895A (en) | 1994-10-14 | 1995-10-12 | Use of gaba antagonists in the treatment of emesis |
Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
GB9420784A GB9420784D0 (en) | 1994-10-14 | 1994-10-14 | Medicaments |
Publications (2)
Publication Number | Publication Date |
---|---|
WO1996011680A2 true WO1996011680A2 (en) | 1996-04-25 |
WO1996011680A3 WO1996011680A3 (en) | 1996-06-27 |
Family
ID=10762886
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP1995/004025 WO1996011680A2 (en) | 1994-10-14 | 1995-10-12 | Use of gaba agonists in the treatment of emesis |
Country Status (3)
Country | Link |
---|---|
AU (1) | AU3745895A (en) |
GB (1) | GB9420784D0 (en) |
WO (1) | WO1996011680A2 (en) |
Cited By (13)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1999008670A1 (en) * | 1997-08-20 | 1999-02-25 | Guglietta, Antonio | Gaba analogs to prevent and treat gastrointestinal damage |
EP0974351A2 (en) * | 1998-04-24 | 2000-01-26 | Jouveinal | Medicament for preventing and treating gastrointestinal damage |
EP1031350A1 (en) * | 1999-02-23 | 2000-08-30 | Warner-Lambert Company | Use of a gabapentin-analog for the manufacture of a medicament for preventing and treating visceral pain |
US6127418A (en) * | 1997-08-20 | 2000-10-03 | Warner-Lambert Company | GABA analogs to prevent and treat gastrointestinal damage |
US6576626B2 (en) | 1999-12-09 | 2003-06-10 | Astrazeneca Ab | Aminopropylphosphinic acids |
US6596711B1 (en) | 1999-12-09 | 2003-07-22 | Astrazeneca Ab | (Aminopropyl)methylphosphinic acids |
WO2005025559A1 (en) * | 2003-09-12 | 2005-03-24 | Agi Therapeutics Ltd. | Treatment of gastroparesis and nonulcer dyspepsia with gabab agonists |
US6919379B2 (en) | 2001-06-08 | 2005-07-19 | Astrazeneca Ab | Compounds useful in reflux disease |
US7309719B1 (en) * | 1998-05-15 | 2007-12-18 | Warner Lambert Company, Llc | Stabilized pharmaceutical preparation of gamma-aminobutyric acid derivatives and process for preparing the same |
US7319095B2 (en) | 1999-12-09 | 2008-01-15 | Astrazeneca Ab | Use of GABAB receptor agonists |
US10556914B2 (en) | 2015-09-15 | 2020-02-11 | Abbvie Inc. | Substituted isoxazolopyridazinones and isothiazolopyridazinones and methods of use |
CN111603560A (en) * | 2020-06-22 | 2020-09-01 | 泉州台商投资区秋鑫茶业有限公司 | Application of tea gamma-aminobutyric acid in tumor radiotherapy |
US10918632B2 (en) * | 2016-09-07 | 2021-02-16 | The Children's Hospital Of Philadelphia | Nonselective metabotropic glutamate receptor activators for treatment of anorexia nervosa and binge eating disorder |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
SI0934061T1 (en) | 1996-07-24 | 2003-10-31 | Warner-Lambert Company Llc | Isobutylgaba and its derivatives for the treatment of pain |
Citations (9)
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US3896149A (en) * | 1972-06-07 | 1975-07-22 | Sakai Chemical Industry Co | Novel pyrrolidone derivatives and manufacturing the same |
EP0082369A1 (en) * | 1981-12-19 | 1983-06-29 | MERCK PATENT GmbH | Imidazo (4,5-c) pyridines, pharmaceutical compositions containing them and process for their preparation |
GB2185483A (en) * | 1986-01-21 | 1987-07-22 | Nippon Shinyaku Co Ltd | Pyroglutamide derivatives |
US4952573A (en) * | 1988-03-23 | 1990-08-28 | Laboratoirs Alcon S.A. | Compounds having GABA like activity, and use of same in tissue irrigating solutions |
US5182290A (en) * | 1991-08-27 | 1993-01-26 | Neurogen Corporation | Certain oxazoloquinolinones; a new class of GABA brain receptor ligands |
WO1993011138A1 (en) * | 1991-12-02 | 1993-06-10 | John Wyeth & Brother Limited | Amine derivatives containing a phosphonic, phosphonous or phosphinic acid moiety |
WO1993022314A1 (en) * | 1992-04-30 | 1993-11-11 | Neurogen Corporation | Certain aryl and cycloalkyl fused imidazopyrazinediones; a new class of gaba brain receptor ligands |
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WO1994025016A1 (en) * | 1993-04-23 | 1994-11-10 | Glaxo Group Limited | Novel medical use for gaba agonists |
-
1994
- 1994-10-14 GB GB9420784A patent/GB9420784D0/en active Pending
-
1995
- 1995-10-12 WO PCT/EP1995/004025 patent/WO1996011680A2/en active Application Filing
- 1995-10-12 AU AU37458/95A patent/AU3745895A/en not_active Abandoned
Patent Citations (9)
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US3896149A (en) * | 1972-06-07 | 1975-07-22 | Sakai Chemical Industry Co | Novel pyrrolidone derivatives and manufacturing the same |
EP0082369A1 (en) * | 1981-12-19 | 1983-06-29 | MERCK PATENT GmbH | Imidazo (4,5-c) pyridines, pharmaceutical compositions containing them and process for their preparation |
GB2185483A (en) * | 1986-01-21 | 1987-07-22 | Nippon Shinyaku Co Ltd | Pyroglutamide derivatives |
US4952573A (en) * | 1988-03-23 | 1990-08-28 | Laboratoirs Alcon S.A. | Compounds having GABA like activity, and use of same in tissue irrigating solutions |
US5281747A (en) * | 1989-05-13 | 1994-01-25 | Ciba-Geigy Corporation | Substituted aminoalkylphosphinic acids |
US5182290A (en) * | 1991-08-27 | 1993-01-26 | Neurogen Corporation | Certain oxazoloquinolinones; a new class of GABA brain receptor ligands |
WO1993011138A1 (en) * | 1991-12-02 | 1993-06-10 | John Wyeth & Brother Limited | Amine derivatives containing a phosphonic, phosphonous or phosphinic acid moiety |
WO1993022314A1 (en) * | 1992-04-30 | 1993-11-11 | Neurogen Corporation | Certain aryl and cycloalkyl fused imidazopyrazinediones; a new class of gaba brain receptor ligands |
WO1994025016A1 (en) * | 1993-04-23 | 1994-11-10 | Glaxo Group Limited | Novel medical use for gaba agonists |
Non-Patent Citations (1)
Title |
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LANCET, 1983 page 227 XP 000563383 'Baclofen for intractable vomiting in muscular dystrophy' cited in the application * |
Cited By (22)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1999008671A1 (en) * | 1997-08-20 | 1999-02-25 | Warner-Lambert Company | Gaba analogs to prevent and treat gastrointestinal damage |
US6127418A (en) * | 1997-08-20 | 2000-10-03 | Warner-Lambert Company | GABA analogs to prevent and treat gastrointestinal damage |
US6242488B1 (en) | 1997-08-20 | 2001-06-05 | University Of Oklahoma | Method for preventing and treating pain |
JP2001515033A (en) * | 1997-08-20 | 2001-09-18 | ワーナー−ランバート・カンパニー | GABA analogs for preventing and treating gastrointestinal damage |
US6426368B2 (en) | 1997-08-20 | 2002-07-30 | Warner-Lambert Company | Method for preventing and treating alcoholism |
WO1999008670A1 (en) * | 1997-08-20 | 1999-02-25 | Guglietta, Antonio | Gaba analogs to prevent and treat gastrointestinal damage |
EP0974351A2 (en) * | 1998-04-24 | 2000-01-26 | Jouveinal | Medicament for preventing and treating gastrointestinal damage |
EP0974351A3 (en) * | 1998-04-24 | 2000-12-13 | Jouveinal | Medicament for preventing and treating gastrointestinal damage |
US7309719B1 (en) * | 1998-05-15 | 2007-12-18 | Warner Lambert Company, Llc | Stabilized pharmaceutical preparation of gamma-aminobutyric acid derivatives and process for preparing the same |
EP1031350A1 (en) * | 1999-02-23 | 2000-08-30 | Warner-Lambert Company | Use of a gabapentin-analog for the manufacture of a medicament for preventing and treating visceral pain |
WO2000050027A1 (en) * | 1999-02-23 | 2000-08-31 | Warner-Lambert Company | Gabapentin derivative for preventing and treating visceral pain |
US6576626B2 (en) | 1999-12-09 | 2003-06-10 | Astrazeneca Ab | Aminopropylphosphinic acids |
US6841698B2 (en) | 1999-12-09 | 2005-01-11 | Astrazeneca Ab | Aminopropylphosphinic acids |
US7034176B2 (en) | 1999-12-09 | 2006-04-25 | Astrazeneca Ab | Aminopropylphosphinic acids |
US6596711B1 (en) | 1999-12-09 | 2003-07-22 | Astrazeneca Ab | (Aminopropyl)methylphosphinic acids |
US7319095B2 (en) | 1999-12-09 | 2008-01-15 | Astrazeneca Ab | Use of GABAB receptor agonists |
US7807658B2 (en) | 1999-12-09 | 2010-10-05 | Astrazeneca Ab | Use of GabaB receptor agonists |
US6919379B2 (en) | 2001-06-08 | 2005-07-19 | Astrazeneca Ab | Compounds useful in reflux disease |
WO2005025559A1 (en) * | 2003-09-12 | 2005-03-24 | Agi Therapeutics Ltd. | Treatment of gastroparesis and nonulcer dyspepsia with gabab agonists |
US10556914B2 (en) | 2015-09-15 | 2020-02-11 | Abbvie Inc. | Substituted isoxazolopyridazinones and isothiazolopyridazinones and methods of use |
US10918632B2 (en) * | 2016-09-07 | 2021-02-16 | The Children's Hospital Of Philadelphia | Nonselective metabotropic glutamate receptor activators for treatment of anorexia nervosa and binge eating disorder |
CN111603560A (en) * | 2020-06-22 | 2020-09-01 | 泉州台商投资区秋鑫茶业有限公司 | Application of tea gamma-aminobutyric acid in tumor radiotherapy |
Also Published As
Publication number | Publication date |
---|---|
GB9420784D0 (en) | 1994-11-30 |
AU3745895A (en) | 1996-05-06 |
WO1996011680A3 (en) | 1996-06-27 |
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