WO1994001095A2 - Medicaments pour le traitement de douleurs viscerales et de migraines - Google Patents

Medicaments pour le traitement de douleurs viscerales et de migraines Download PDF

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Publication number
WO1994001095A2
WO1994001095A2 PCT/GB1993/001377 GB9301377W WO9401095A2 WO 1994001095 A2 WO1994001095 A2 WO 1994001095A2 GB 9301377 W GB9301377 W GB 9301377W WO 9401095 A2 WO9401095 A2 WO 9401095A2
Authority
WO
WIPO (PCT)
Prior art keywords
dose
receptor antagonist
treatment
composition according
active
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.)
Ceased
Application number
PCT/GB1993/001377
Other languages
English (en)
Other versions
WO1994001095A3 (fr
Inventor
Gareth John Sanger
Stephen Edward Banner
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
SmithKline Beecham Ltd
Original Assignee
SmithKline Beecham Ltd
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by SmithKline Beecham Ltd filed Critical SmithKline Beecham Ltd
Priority to AU45076/93A priority Critical patent/AU4507693A/en
Priority to EP93914854A priority patent/EP0650355A1/fr
Priority to CA002139440A priority patent/CA2139440A1/fr
Priority to JP6503078A priority patent/JPH07508530A/ja
Publication of WO1994001095A2 publication Critical patent/WO1994001095A2/fr
Publication of WO1994001095A3 publication Critical patent/WO1994001095A3/fr
Priority to KR1019940704887A priority patent/KR950702112A/ko
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • 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
    • A61K31/16—Amides, e.g. hydroxamic acids
    • A61K31/165—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide
    • 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
    • A61K31/166—Amides, e.g. hydroxamic acids having aromatic rings, e.g. colchicine, atenolol, progabide having the carbon of a carboxamide group directly attached to the aromatic ring, e.g. procainamide, procarbazine, metoclopramide, labetalol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive 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
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • 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
    • A61P25/06—Antimigraine agents

Definitions

  • This invention relates to the use of certain compounds which are 5-HT3 receptor antagonists as visceral analgesics.
  • EP-A-279512 (Beecham Group p.l.c.) describes the use of certain 5-HT3 receptor antagonists, including granisetron (KYTRIL) in the treatment of visceral pain.
  • KYTRIL granisetron
  • Visceral pain is a symptom of irritable bowel syndrome (IBS) and granisetron has been found to desensitise the rectum in IBS patients as shown by double-blind placebo-controlled studies, at doses of 120 ⁇ g/kg and 50 ⁇ g/kg, 120 ⁇ g/kg being most effective. (Prior and Read, 1990; Gut 11 (10) A1174).
  • Granisetron has been found to be active in an animal model of rectal sensitivity to distension (see method described hereafter).
  • 5-HT3 receptor antagonists which have the same effect as granisetron in this model, include zatosetron (Lilly) and metoclopramide.
  • the invention therefore relates to the use of those 5-HT3 receptor antagonists, which are active in the animal model at a dose determined as the dose at which 5-HT3 receptor antagonist activity is observed in standard tests, such as the Bezold-Jarisch model, in the treatment of visceral pain, such as the pain symptoms of IBS, and also migraine.
  • Preferred compounds are active at a lower dose than the 5-HT3 receptor antagonist dose.
  • Compounds which are approved or under clinical investigation are active at a similar dosage level to that which is used for antiemetic use.
  • 5-HT3 receptor antagonists which should be considered for this invention include those specifically and generically disclosed and referenced in EP-A-450757 (Glaxo Group Limited). Rat Model of Colo-rectal Distension
  • a 6-7 cm latex balloon was inserted intra-anally into male Wistar rats (250-650g) under halothane anaesthesia; the balloon catheter was taped to the tail. After recovery the animals were allowed unrestricted movement and were dosed with either vehicle (saline) or 5-hydroxytryptophan (5-HTP lOmgkg " ! subcutaneously).
  • vehicle saline
  • 5-hydroxytryptophan 5-hydroxytryptophan
  • 5-HT3 receptor antagonists or saline were dosed subcutaneously after 3 stable responses were achieved and within 45 min of dosing 5-HTP or vehicle.
  • the visceromotor threshold values were then recorded for a further 30 min.
  • a similar model was described by Ness & Gebhart (1988, Brain Res. 450. 153-169). Maximum percentage changes (within the 30 min post-dose period) in distension pressure were compared with the mean of the pre-dose recordings. Saline control values were then assigned the value of 1.00 and drug induced changes compared directly.
  • Intrathecal administration of granisetron also showed good analgesic activity suggesting that a site of action, of those 5-HT3 receptor antagonists that are visceral analgesics, may be in the spinal cord.
  • 5-HT3 receptor antagonists that are visceral analgesics

Landscapes

  • Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Epidemiology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Engineering & Computer Science (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Neurosurgery (AREA)
  • Pain & Pain Management (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

Abstract

L'invention porte sur l'utilisation des antagonistes du récepteur de 5-HT3 qui sont actifs sur un modèle rat de distension colo-rectale à une dose déterminée à laquelle on observe l'activité de l'antagoniste du récepteur de 5-HT3 dans les essais standard tels que le modèle Bezold-Jarisch, dans le traitement de douleurs viscérales telles que les symptômes douloureux du côlon irritable et de la migraine.
PCT/GB1993/001377 1992-07-03 1993-06-30 Medicaments pour le traitement de douleurs viscerales et de migraines Ceased WO1994001095A2 (fr)

Priority Applications (5)

Application Number Priority Date Filing Date Title
AU45076/93A AU4507693A (en) 1992-07-03 1993-06-30 Medicaments for the treatment of visceral pain and migraine
EP93914854A EP0650355A1 (fr) 1992-07-03 1993-06-30 Medicaments pour le traitement de douleurs viscerales et de migraines
CA002139440A CA2139440A1 (fr) 1992-07-03 1993-06-30 Medicaments pour le traitement des douleurs viscerales et de la migraine
JP6503078A JPH07508530A (ja) 1992-07-03 1993-06-30 内臓の痛みおよび偏頭痛の治療薬
KR1019940704887A KR950702112A (ko) 1992-07-03 1994-12-31 내장 진통 및 편두통의 치료 약물(Medicaments for the treatment of visceral pain and migraine)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB9214184.5 1992-07-03
GB929214184A GB9214184D0 (en) 1992-07-03 1992-07-03 Pharmaceuticals

Publications (2)

Publication Number Publication Date
WO1994001095A2 true WO1994001095A2 (fr) 1994-01-20
WO1994001095A3 WO1994001095A3 (fr) 1994-04-14

Family

ID=10718169

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB1993/001377 Ceased WO1994001095A2 (fr) 1992-07-03 1993-06-30 Medicaments pour le traitement de douleurs viscerales et de migraines

Country Status (7)

Country Link
EP (1) EP0650355A1 (fr)
JP (1) JPH07508530A (fr)
KR (1) KR950702112A (fr)
AU (1) AU4507693A (fr)
CA (1) CA2139440A1 (fr)
GB (1) GB9214184D0 (fr)
WO (1) WO1994001095A2 (fr)

Cited By (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5726187A (en) * 1992-10-16 1998-03-10 Smithkline Beecham Plc N-alkylpiperidinyl-4-methyl carboxylic esters/amides of condensed ring systems as 5-HT4 receptor antagonists
US5852014A (en) * 1992-03-12 1998-12-22 Smithkline Beecham P.L.C. Condensed indole derivatives as 5HT4 -receptor antagonists
WO1999017755A3 (fr) * 1997-10-07 1999-09-23 Glaxo Group Ltd Medicaments
US5998409A (en) * 1992-03-12 1999-12-07 Smithkline Beecham Plc Condensed indole derivatives as 5HT4 -receptor antagonists
WO2000048581A3 (fr) * 1999-02-18 2001-01-11 Novartis Ag Utilisation d'antagonistes du recepteur 5-ht¿3?
WO2001041748A3 (fr) * 1999-12-10 2002-12-19 Novartis Ag Combinaisons pharmaceutiques et leur utilisation dans le traitement de troubles gastro-intestinaux
US7094786B2 (en) 2003-01-13 2006-08-22 Dynogen Pharmaceuticals, Inc. Method of treating nausea, vomiting, retching or any combination thereof
US7470690B2 (en) 2002-07-10 2008-12-30 Dynogen Pharmaceuticals, Inc. 4-(2-Fluorophenyl)-6-methyl-2-(1-piperazinyl)thieno[2,3-D)pyrimidine in the treatment of functional bowel disorder
US7608282B2 (en) * 2003-02-05 2009-10-27 Strakan International Limited Transdermal granisetron
US8246981B2 (en) 2005-05-18 2012-08-21 Abeille Pharamaceuticals, Inc. Transdermal method and patch for emesis

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE19807535A1 (de) * 1998-02-21 1999-08-26 Asta Medica Ag Pharmazeutische Kombinationen mit Tramadol

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ATE86110T1 (de) * 1984-12-20 1993-03-15 Sandoz Ag Behandlung von gastrointestinalkrankheiten durch anwendung von 5-ht3-antagonisten.
GB8617994D0 (en) * 1986-07-23 1986-08-28 Glaxo Group Ltd Heterocyclic compounds
EP0254584B1 (fr) * 1986-07-25 1992-10-07 Beecham Group Plc Composés azabicycliques, procédé pour leur préparation et leur utilisation pharmaceutique
GB8623819D0 (en) * 1986-10-03 1986-11-05 Glaxo Group Ltd Heterocyclic compounds
GB8812002D0 (en) * 1988-05-20 1988-06-22 Glaxo Group Ltd Chemical compounds
GB8630080D0 (en) * 1986-12-17 1987-01-28 Glaxo Group Ltd Medicaments
GB8806990D0 (en) * 1988-03-23 1988-04-27 Beecham Group Plc Novel compounds
GB8701022D0 (en) * 1987-01-19 1987-02-18 Beecham Group Plc Treatment
DE3852145T2 (de) * 1987-02-18 1995-04-06 Beecham Group Plc Indolderivate, Verfahren zu deren Herstellung und pharmazeutische Präparate, die diese enthalten.
EP0289170B1 (fr) * 1987-04-25 1993-06-23 Beecham Group Plc Composés azabicycliques, leur procédé de préparation et compositions pharmaceutiques les contenant
GB8723157D0 (en) * 1987-10-02 1987-11-04 Beecham Group Plc Compounds
JPH01258673A (ja) * 1987-10-22 1989-10-16 Glaxo Group Ltd ケトン誘導体
ATE108791T1 (de) * 1987-11-04 1994-08-15 Beecham Group Plc Neue 4-oxobenzotriazine und 4-oxochinazoline.
EP0336759A1 (fr) * 1988-04-07 1989-10-11 Glaxo Group Limited Dérivés d'imidazole
GB8814277D0 (en) * 1988-06-16 1988-07-20 Glaxo Group Ltd Chemical compounds
IT1226389B (it) * 1988-07-12 1991-01-15 Angeli Inst Spa Nuovi derivati ammidinici e guanidinici
US5017573A (en) * 1988-07-29 1991-05-21 Dainippon Pharmaceutical Co., Ltd. Indazole-3-carboxylic acid derivatives
EP0356098A3 (fr) * 1988-08-15 1990-07-25 Glaxo Group Limited Dérivés de lactames
GB8820650D0 (en) * 1988-09-01 1988-10-05 Glaxo Group Ltd Medicaments
US5173493A (en) * 1988-09-27 1992-12-22 Fujisawa Pharmaceutical Company, Ltd. Pyridoindole derivatives and processes for preparation thereof
AU627221B2 (en) * 1988-09-27 1992-08-20 Fujisawa Pharmaceutical Co., Ltd. Pyridoindole derivatives and processes for preparation thereof
GB8823980D0 (en) * 1988-10-13 1988-11-23 Glaxo Group Ltd Chemical compounds
GB8829079D0 (en) * 1988-12-13 1989-01-25 Beecham Group Plc Novel compounds
CA2004911A1 (fr) * 1988-12-22 1990-06-22 Mitsuaki Ohta Derives de 4,5,6,7-tetrahydrobenzimidazole
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US5126343A (en) * 1989-09-11 1992-06-30 G. D. Searle & Co. N-azabicyclo [3.3.0]octane amides of aromatic acids
WO1991007402A1 (fr) * 1989-11-17 1991-05-30 Pfizer Inc. Amides et esters azabicyliques antagonistes du recepteur de 5-ht¿3?
DK40890D0 (da) * 1990-02-16 1990-02-16 Ferrosan As Substituerede urinstofforbindelser, deres fremstilling og anvendelse
EP0450757A3 (en) * 1990-02-22 1993-09-15 Glaxo Group Limited Use of 5-hydroxytryptamine-antagonists in the treatment of mental disorders originating in childhood
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US5260303A (en) * 1991-03-07 1993-11-09 G. D. Searle & Co. Imidazopyridines as serotonergic 5-HT3 antagonists
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Cited By (21)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5852014A (en) * 1992-03-12 1998-12-22 Smithkline Beecham P.L.C. Condensed indole derivatives as 5HT4 -receptor antagonists
US5998409A (en) * 1992-03-12 1999-12-07 Smithkline Beecham Plc Condensed indole derivatives as 5HT4 -receptor antagonists
US5726187A (en) * 1992-10-16 1998-03-10 Smithkline Beecham Plc N-alkylpiperidinyl-4-methyl carboxylic esters/amides of condensed ring systems as 5-HT4 receptor antagonists
WO1999017755A3 (fr) * 1997-10-07 1999-09-23 Glaxo Group Ltd Medicaments
US6284770B1 (en) 1997-10-07 2001-09-04 Glaxo Wellcome Inc. Medicaments for the treatment of non-constipated female irritable bowel syndrome
US6429209B2 (en) 1997-10-07 2002-08-06 Smithkline Beecham Corporation Methods for treating irritable bowel syndrome
US6593336B2 (en) 1997-10-07 2003-07-15 Smithkline Beecham Corporation Methods for treating irritable bowel syndrome
WO2000048581A3 (fr) * 1999-02-18 2001-01-11 Novartis Ag Utilisation d'antagonistes du recepteur 5-ht¿3?
US6462065B2 (en) 1999-02-18 2002-10-08 Novartis Ag Use of 5-HT3 receptor antagonists for treating musculoeskeletal diseases
US7393857B2 (en) 1999-02-18 2008-07-01 Novasearch Ag Use of 5-HT3 receptor antagonists for treating musculoskeletal diseases
EP1488788A1 (fr) * 1999-12-10 2004-12-22 Novartis AG Combinaisons pharmaceutiques et leur utilisation pour le traitement de troubles gastro-intestinaux
CN1310644C (zh) * 1999-12-10 2007-04-18 诺瓦提斯公司 药物组合产品及其在治疗胃肠疾病中的应用
WO2001041748A3 (fr) * 1999-12-10 2002-12-19 Novartis Ag Combinaisons pharmaceutiques et leur utilisation dans le traitement de troubles gastro-intestinaux
SG152025A1 (en) * 1999-12-10 2009-05-29 Novartis Ag Pharmaceutical combinations and their use in treating gastrointestinal disorders
CZ300690B6 (cs) * 1999-12-10 2009-07-15 Novartis Ag Farmaceutická kombinace obsahující tegaserod a omeprazol pro lécení refluxní nemoci jícnu
US7470690B2 (en) 2002-07-10 2008-12-30 Dynogen Pharmaceuticals, Inc. 4-(2-Fluorophenyl)-6-methyl-2-(1-piperazinyl)thieno[2,3-D)pyrimidine in the treatment of functional bowel disorder
US7094786B2 (en) 2003-01-13 2006-08-22 Dynogen Pharmaceuticals, Inc. Method of treating nausea, vomiting, retching or any combination thereof
US7608282B2 (en) * 2003-02-05 2009-10-27 Strakan International Limited Transdermal granisetron
US20100008974A1 (en) * 2003-02-05 2010-01-14 Strakan International Limited Transdermal granisetron
US20120258164A1 (en) * 2003-02-05 2012-10-11 Strakan International Limited Transdermal granisetron
US8246981B2 (en) 2005-05-18 2012-08-21 Abeille Pharamaceuticals, Inc. Transdermal method and patch for emesis

Also Published As

Publication number Publication date
GB9214184D0 (en) 1992-08-12
EP0650355A1 (fr) 1995-05-03
KR950702112A (ko) 1995-06-19
AU4507693A (en) 1994-01-31
WO1994001095A3 (fr) 1994-04-14
JPH07508530A (ja) 1995-09-21
CA2139440A1 (fr) 1994-01-20

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