Title:
USE OF 5-HT¿3? RECEPTOR ANTAGONISTS FOR TREATING MUSCULOESKELETAL DISEASES
Document Type and Number:
WIPO Patent Application WO/2000/048581
Kind Code:
A2
Abstract:
The present invention relates to a new use for compounds having 5-HT¿3? (serotonin M) receptor antagonist activity, especially tropisetron, for the manufacture of a pharmaceutical composition for the treatment of a non-inflammatory local disease of the musculo-skeletal system, of a local irritation condition of a joint or tendon sheath, or for the local treatment of a local manifestation at the locomotor apparatus of an inflammatory disease except for a crystal induced arthritis and a living pathogen induced inflammatory disease condition as long as the living pathogen is still present.
Inventors:
MUELLER WOLFGANG (CH)
STRATZ THOMAS (DE)
FAERBER LOTHAR (DE)
STRATZ THOMAS (DE)
FAERBER LOTHAR (DE)
Application Number:
PCT/EP2000/001269
Publication Date:
August 24, 2000
Filing Date:
February 16, 2000
Export Citation:
Assignee:
NOVARTIS AG (CH)
NOVARTIS ERFIND VERWALT GMBH (AT)
MUELLER WOLFGANG (CH)
STRATZ THOMAS (DE)
FAERBER LOTHAR (DE)
NOVARTIS ERFIND VERWALT GMBH (AT)
MUELLER WOLFGANG (CH)
STRATZ THOMAS (DE)
FAERBER LOTHAR (DE)
International Classes:
A61K45/00; A61K31/00; A61K31/417; A61K31/4178; A61K31/4184; A61K31/437; A61K31/439; A61K31/46; A61K31/57; A61K31/573; A61P17/02; A61P19/02; A61P19/04; A61P19/08; A61P21/00; A61P29/00; A61P35/00; (IPC1-7): A61K31/00
Domestic Patent References:
| WO2000048597A1 | 2000-08-24 | |||
| WO1994001095A2 | 1994-01-20 |
Foreign References:
| EP0507637A2 | 1992-10-07 |
Other References:
DATABASE BIOSIS [Online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; October 1998 (1998-10) FUJII Y ET AL: "Prophylactic antiemetic therapy with granisetron-dexamethasone combination in women undergoing breast surgery." Database accession no. PREV199800515648 XP002149133 & ACTA ANAESTHESIOLOGICA SCANDINAVICA, vol. 42, no. 9, October 1998 (1998-10), pages 1038-1042, ISSN: 0001-5172
DATABASE BIOSIS [Online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; 31 July 1998 (1998-07-31) GIORDANO JAMES ET AL: "Topical ondansetron attenuates nociceptive and inflammatory effects of intradermal capsaicin in humans." Database accession no. PREV199800438279 XP002149134 & EUROPEAN JOURNAL OF PHARMACOLOGY, vol. 354, no. 1, 31 July 1998 (1998-07-31), pages R13-R14, ISSN: 0014-2999
DATABASE BIOSIS [Online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; 1996 PRAMANIK S S ET AL: "Serotonin-3 (5HT-3) receptor antagonists modulate antinociceptive responses in mice." Database accession no. PREV199799649054 XP002149135 & INDIAN JOURNAL OF PHYSIOLOGY AND ALLIED SCIENCES, vol. 50, no. 4, 1996, pages 168-172, ISSN: 0367-8350
DATABASE BIOSIS [Online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; 1996 SAMBORSKI WLODZIMIERZ ET AL: "The 5-HT-3 blockers in the treatment of the primary fibromyalgia syndrome: A 10-day open study with tropisetron at a low dose." Database accession no. PREV199799477436 XP002149136 & MATERIA MEDICA POLONA, vol. 28, no. 1, 1996, pages 17-19, ISSN: 0025-5246
DATABASE BIOSIS [Online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; 1996 FUJII YOSHITAKA ET AL: "Granisetron and dexamethasone provide more improved prevention of postoperative emesis than granisetron alone in children." Database accession no. PREV199799339428 XP002149137 & CANADIAN JOURNAL OF ANAESTHESIA, vol. 43, no. 12, 1996, pages 1229-1232, ISSN: 0832-610X
DATABASE BIOSIS [Online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; 1995 MOSER PAUL C: "The effect of 5-HT-3 receptor antagonists on the writhing response in mice." Database accession no. PREV199598457877 XP002149138 & GENERAL PHARMACOLOGY, vol. 26, no. 6, 1995, pages 1301-1306, ISSN: 0306-3623
DATABASE BIOSIS [Online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; 1994 SCHWOERER H ET AL: "Treatment of acute gouty arthritis with the 5-hydroxytryptamine antagonist ondansetron." Database accession no. PREV199598040148 XP002149139 & CLINICAL INVESTIGATOR, vol. 72, no. 10, 1994, pages 811-813, ISSN: 0941-0198
DATABASE BIOSIS [Online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; 1989 GIORDANO J ET AL: "PERIPHERALLY ADMINISTERED SEROTONIN 5-HT-3 RECEPTOR ANTAGONISTS REDUCE INFLAMMATORY PAIN IN RATS" Database accession no. PREV199089030180 XP002149140 & EUROPEAN JOURNAL OF PHARMACOLOGY, vol. 170, no. 1-2, 1989, pages 83-86, ISSN: 0014-2999
DATABASE BIOSIS [Online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; 1989 GIORDANO J ET AL: "DIFFERENTIAL ANALGESIC ACTIONS OF SEROTONIN 5-HT-3 RECEPTOR ANTAGONISTS IN THE MOUSE" Database accession no. PREV198988019024 XP002149141 & NEUROPHARMACOLOGY, vol. 28, no. 4, 1989, pages 423-428, ISSN: 0028-3908
DATABASE BIOSIS [Online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; 1989 ESCHALIER A ET AL: "INFLUENCE OF A SPECIFIC 5-HT-3 ANTAGONIST ON CARRAGEENAN-INDUCED HYPERALGESIA IN RATS" Database accession no. PREV198987128603 XP002149142 & PAIN, vol. 36, no. 2, 1989, pages 249-256, ISSN: 0304-3959
DOAK G J ET AL: "FORMALIN-INDUCED NOCICEPTIVE BEHAVIOR AND EDEMA: INVOLVEMENT OF MULTIPLE PERIPHERAL 5-HYDROXYTRYPTAMINE RECEPTOR SUBTYPES" NEUROSCIENCE,US,NEW YORK, NY, vol. 80, no. 3, 1997, pages 939-949, XP000886556 ISSN: 0306-4522
ROSENSTEIN D M ET AL: "ANTINOCICEPTIVE EFFECTS OF MICRODIALYSIS ADMINISTRATION OF 5-HT1A AND 5-HT RECEPTOR AGONISTS AND ANTAGONISTS IN A MODEL OF ACUTE ARTHRITIS" SOCIETY FOR NEUROSCIENCE ABSTRACTS,US,SOCIETY FOR NEUROSCIENCE, vol. 23, no. 23, 1997, page 1540 XP000886228 ISSN: 0190-5295
CUNNINGHAM D ET AL: "OPTIMUM ANTI-EMETIC THERAPY FOR CISPLATIN INDUCED EMESIS OVER REPEAT COURSES: ONDANSETRON PLUS DEXAMETHASONE COMPARED WITH METOCLOPRAMIDE, DEXAMETHASONE PLUS LORAZEPAM" ANNALS OF ONCOLOGY,NL,KLUWER, DORDRECHT, vol. 7, no. 3, 1996, pages 277-282, XP000886538 ISSN: 0923-7534
DATABASE BIOSIS [Online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; 1998 BOTELLA A ET AL: "Intracolonic glycerol induces abdominal contractions in rats: Role of 5-HT3 receptors." Database accession no. PREV199900012906 XP002149157 & FUNDAMENTAL & CLINICAL PHARMACOLOGY, vol. 12, no. 6, 1998, pages 619-623, ISSN: 0767-3981
DATABASE BIOSIS [Online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; 1998 SAMBORSKI WLODZIMIERZ ET AL: "New concept of pharmacological treatment of fibromyalgia. Do exist two subgroups of fibromyalgia patients?" Database accession no. PREV199800453416 XP002149158 & REUMATOLOGIA (WARSAW), vol. 36, no. 2, 1998, pages 144-150, ISSN: 0034-6233
DATABASE BIOSIS [Online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; 31 July 1998 (1998-07-31) GIORDANO JAMES ET AL: "Topical ondansetron attenuates nociceptive and inflammatory effects of intradermal capsaicin in humans." Database accession no. PREV199800438279 XP002149134 & EUROPEAN JOURNAL OF PHARMACOLOGY, vol. 354, no. 1, 31 July 1998 (1998-07-31), pages R13-R14, ISSN: 0014-2999
DATABASE BIOSIS [Online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; 1996 PRAMANIK S S ET AL: "Serotonin-3 (5HT-3) receptor antagonists modulate antinociceptive responses in mice." Database accession no. PREV199799649054 XP002149135 & INDIAN JOURNAL OF PHYSIOLOGY AND ALLIED SCIENCES, vol. 50, no. 4, 1996, pages 168-172, ISSN: 0367-8350
DATABASE BIOSIS [Online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; 1996 SAMBORSKI WLODZIMIERZ ET AL: "The 5-HT-3 blockers in the treatment of the primary fibromyalgia syndrome: A 10-day open study with tropisetron at a low dose." Database accession no. PREV199799477436 XP002149136 & MATERIA MEDICA POLONA, vol. 28, no. 1, 1996, pages 17-19, ISSN: 0025-5246
DATABASE BIOSIS [Online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; 1996 FUJII YOSHITAKA ET AL: "Granisetron and dexamethasone provide more improved prevention of postoperative emesis than granisetron alone in children." Database accession no. PREV199799339428 XP002149137 & CANADIAN JOURNAL OF ANAESTHESIA, vol. 43, no. 12, 1996, pages 1229-1232, ISSN: 0832-610X
DATABASE BIOSIS [Online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; 1995 MOSER PAUL C: "The effect of 5-HT-3 receptor antagonists on the writhing response in mice." Database accession no. PREV199598457877 XP002149138 & GENERAL PHARMACOLOGY, vol. 26, no. 6, 1995, pages 1301-1306, ISSN: 0306-3623
DATABASE BIOSIS [Online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; 1994 SCHWOERER H ET AL: "Treatment of acute gouty arthritis with the 5-hydroxytryptamine antagonist ondansetron." Database accession no. PREV199598040148 XP002149139 & CLINICAL INVESTIGATOR, vol. 72, no. 10, 1994, pages 811-813, ISSN: 0941-0198
DATABASE BIOSIS [Online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; 1989 GIORDANO J ET AL: "PERIPHERALLY ADMINISTERED SEROTONIN 5-HT-3 RECEPTOR ANTAGONISTS REDUCE INFLAMMATORY PAIN IN RATS" Database accession no. PREV199089030180 XP002149140 & EUROPEAN JOURNAL OF PHARMACOLOGY, vol. 170, no. 1-2, 1989, pages 83-86, ISSN: 0014-2999
DATABASE BIOSIS [Online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; 1989 GIORDANO J ET AL: "DIFFERENTIAL ANALGESIC ACTIONS OF SEROTONIN 5-HT-3 RECEPTOR ANTAGONISTS IN THE MOUSE" Database accession no. PREV198988019024 XP002149141 & NEUROPHARMACOLOGY, vol. 28, no. 4, 1989, pages 423-428, ISSN: 0028-3908
DATABASE BIOSIS [Online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; 1989 ESCHALIER A ET AL: "INFLUENCE OF A SPECIFIC 5-HT-3 ANTAGONIST ON CARRAGEENAN-INDUCED HYPERALGESIA IN RATS" Database accession no. PREV198987128603 XP002149142 & PAIN, vol. 36, no. 2, 1989, pages 249-256, ISSN: 0304-3959
DOAK G J ET AL: "FORMALIN-INDUCED NOCICEPTIVE BEHAVIOR AND EDEMA: INVOLVEMENT OF MULTIPLE PERIPHERAL 5-HYDROXYTRYPTAMINE RECEPTOR SUBTYPES" NEUROSCIENCE,US,NEW YORK, NY, vol. 80, no. 3, 1997, pages 939-949, XP000886556 ISSN: 0306-4522
ROSENSTEIN D M ET AL: "ANTINOCICEPTIVE EFFECTS OF MICRODIALYSIS ADMINISTRATION OF 5-HT1A AND 5-HT RECEPTOR AGONISTS AND ANTAGONISTS IN A MODEL OF ACUTE ARTHRITIS" SOCIETY FOR NEUROSCIENCE ABSTRACTS,US,SOCIETY FOR NEUROSCIENCE, vol. 23, no. 23, 1997, page 1540 XP000886228 ISSN: 0190-5295
CUNNINGHAM D ET AL: "OPTIMUM ANTI-EMETIC THERAPY FOR CISPLATIN INDUCED EMESIS OVER REPEAT COURSES: ONDANSETRON PLUS DEXAMETHASONE COMPARED WITH METOCLOPRAMIDE, DEXAMETHASONE PLUS LORAZEPAM" ANNALS OF ONCOLOGY,NL,KLUWER, DORDRECHT, vol. 7, no. 3, 1996, pages 277-282, XP000886538 ISSN: 0923-7534
DATABASE BIOSIS [Online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; 1998 BOTELLA A ET AL: "Intracolonic glycerol induces abdominal contractions in rats: Role of 5-HT3 receptors." Database accession no. PREV199900012906 XP002149157 & FUNDAMENTAL & CLINICAL PHARMACOLOGY, vol. 12, no. 6, 1998, pages 619-623, ISSN: 0767-3981
DATABASE BIOSIS [Online] BIOSCIENCES INFORMATION SERVICE, PHILADELPHIA, PA, US; 1998 SAMBORSKI WLODZIMIERZ ET AL: "New concept of pharmacological treatment of fibromyalgia. Do exist two subgroups of fibromyalgia patients?" Database accession no. PREV199800453416 XP002149158 & REUMATOLOGIA (WARSAW), vol. 36, no. 2, 1998, pages 144-150, ISSN: 0034-6233
Attorney, Agent or Firm:
Becker, Konrad (Corporate Intellectual Property Patent &
Trademark Department, Basel, CH)
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Claims:
CLAIMS
| 1. | The use of a 5HT3 receptor antagonist or of a pharmaceutically acceptable salt of such an antagonist for the manufacture of a pharmaceutical composition for the treat ment of a noninflammatory local disease of the musculosceletal system, of a local irritation condition of a joint or tendon sheath, or for the local treatment a local manifestation at the locomotor apparatus of an inflammatory disease except for a crystal induced arthritis and a living pathogen induced inflammatory disease condition as long as the living pathogen is still present. |
| 2. | The use according to claim 1, wherein in addition to pain at least one further sequela or symptom of the local disease, local irritation condition or local manifestation is alleviated, ameliorated or controlled. |
| 3. | The use according to claim 1, wherein the 5HT3 receptor antagonist is selected from the group consisting of ondansetron, granisetron, dolasetron, tropisetron, ramosetron, fabesetron, lintopride and alosetron, which may be used in free form or as a pharmaceutically acceptable salt. |
| 4. | The use according to claim 1, wherein the disease to be treated is a noninflammatory local disease of the musculosceletal system selected from the group consisting of myofasciale syndrome, tendomyosis, tendinosis, insertion tendopathy, bursopathy or periarthropathy, overload syndrome of the muscle, syndromes due to the compression of nerves or neuropathy and algodystrophy. |
| 5. | The use according to claim 1, wherein the disease to be treated is a noninflammatory local disease of the musculosceletal system selected from the group consisting of myofasciale syndrome, tendomyosis, tendinosis, insertion tendopathy, bursopathy or periarthropathy, overload syndrome of the muscle, and syndromes due to the compression of nerves. |
| 6. | The use according to claim 1, wherein the disease to be treated is a local irritation condition of a joint or tendon sheath related to a meniscus lesion, arthrosis, trauma, locally osteochondritis dissecans, osteonecrosis or joint chondromatosis, and various noninflammatory rheumatoid diseases. |
| 7. | The use according to claim 1 for the local treatment a local manifestation at the locomotor apparatus of an inflammatory disease except for a crystal induced arthritis and a living pathogen induced inflammatory disease condition as long as the living pathogen is still present, wherein said inflammatory disease being selected from chronic polyarthritis, sarcoidosis, paraneoplastic syndrome or tumorinduced inflammatory diseases, turbid effusions, collagenosis, postinfectious arthritis, seronegative spondylarthritis and vasculitis. |
| 8. | A method of treating a noninflammatory local disease of the musculosceletal system, of treating a local irritation condition of a joint or tendon sheath, or of locally treating a local manifestation at the locomotor apparatus of an inflammatory disease except for a crystal induced arthritis and a living pathogen induced inflammatory disease condi tion as long as the living pathogen is still present, in a subject in need thereof, which method comprises locally administering to said subject an effective amount of a 5HT3 receptor antagonist. |
| 9. | A method according to claim 8 wherein the 5HT3 antagonist is administrated locally at or near the site of the local disease, local irritation condition or local manifestation. |
| 10. | A method of providing replacement therapy for glucocorticosteroid therapy in a subject receiving such glucocorticosteroid therapy, which method comprises locally administering to said subject an effective amount of a 5HT3receptor antagonist. |
| 11. | A method of treating any process, condition, event or disease as hereinbefore described, in a subject in need thereof, which method comprises locally administering an effective amount of a 5HT3 receptor antagonist together with a glucocorticosteroid. |
| 12. | A pharmaceutical dosage form for local administration comprising a 5HT3 receptor antagonist together with an antiinflammatory glucocorticosteroid. |
| 13. | A 5HT3 receptor antagonist or a pharmaceutical composition comprising a 5HT3 receptor antagonist for local use: a) in the treatment of process, condition, event or disease as hereinbefore described; b) as replacement therapy for antiinflammatory glucocorticosteroid therapy in the treatment of any process, condition, event or disease as hereinbefore described; or c) for coadministration together with a glucocorticosteroid in the treatment of any process, condition, event or disease as hereinbefore described. |
| 14. | A method, use, compound or composition as claimed in any one of claims 1,8,10, 11,12 or 13, wherein the 5HT3 receptor antagonist is tropisetron. |
Description:
INTERNATIONALSEARCHREPORT {x7al Appilcatlon No PCT/EP00/01269 C.(Continuation)DOCUMENTSCONSIDEREDTOBERELEVANT Category ° Citationofdocument,withindication, where appropnate,oftherelevantpassagesRelevanttodaimNo. XDATABASEBIOSIS'Online!1-11,13, BIOSCIENCESINFORMATIONSERVICE,14 PHILADELPHIA,PA,US; 31July1998(1998-07-31) GIORDANOJAMESETAL:"Topicalondansetron attenuatesnociceptiveandinflammatory effectsofintradermalcapsaicinin humans." Databaseaccessionno.PREV199800438279 XP002149134 abstract &EUROPEANJOURNALOFPHARMACOLOGY, vol.354,no.1, 31July1998(1998-07-31),pagesR13-R14, ISSN:0014-2999 XDATABASEBIOSIS'Online!1-11,13, BIOSCIENCESINFORMATIONSERVICE,14 PHILADELPHIA,PA,US;1996 PRAMANIKSSETAL:"Serotonin-3(5HT-3) receptorantagonistsmodulate antinociceptiveresponsesinmice." Databaseaccessionno.PREV199799649054 XP002149135 abstract &INDIANJOURNALOFPHYSIOLOGYANDALLIED SCIENCES, vol.50,no.4,1996,pages168-172, ISSN:0367-8350 XDATABASEBIOSIS'Online!1-11,13, BIOSCIENCESINFORMATIONSERVICE,14 PHILADELPHIA,PA,US;1996 SAMBORSKIWLODZIMIERZETAL:"The5-HT-3 blockersinthetreatmentoftheprimary fibromyalgiasyndrome:A10-dayopenstudy withtropisetronatalowdose." Databaseaccessionno.PREV199799477436 XP002149136 abstract &MATERIAMEDICAPOLONA, vol.28,no.1,1996,pages17-19, ISSN:0025-5246 2 2 INTERNATIONAL SEARCH REPORT Ints malApplcatlon No PCT/EP00/01269 C.(Continuatlon) DOCUMENTS CONSIDEREDTOBERELEVANT CategoryCitationofdocument,withindication,whereappropnate,of
therelevantpassagesRelevanttodaimNo. XDATABASEBIOSIS'Online!11-14 BIOSCIENCESINFORMATIONSERVICE, PHILADELPHIA,PA,US;1996 FUJIIYOSHITAKAETAL:"Granisetronand dexamethasoneprovidemoreimproved preventionofpostoperativeemesisthan granisetronaloneinchildren." Databaseaccessionno.PREV199799339428 XP002149137 abstract &CANADIANJOURNALOFANAESTHESIA, vol.43,no.12,1996,pages1229-1232, ISSN:0832-610X XDATABASEBIOSIS'Online!1-11,13, BIOSCIENCESINFORMATIONSERVICE,14 PHILADELPHIA,PA,US;1995 MOSERPAULC:"Theeffectof5-HT-3 receptorantagonistsonthewrithing responseinmice." Databaseaccessionno.PREV199598457877 XP002149138 abstract &GENERALPHARMACOLOGY, vol.26,no.6,1995,pages1301-1306, ISSN:0306-3623 XDATABASEBIOSIS'Online!1-11,13, BIOSCIENCESINFORMATIONSERVICE,14 PHILADELPHIA,PA,US;1994 SCHWOERERHETAL:"Treatmentofacute goutyarthritiswiththe 5-hydroxytryptamineantagonist ondansetron." Databaseaccessionno.PREV199598040148 XP002149139 abstract &CLINICALINVESTIGATOR, vol.72,no.10,1994,pages811-813, ISSN:0941-0198 XDATABASEBIOSIS'Online!1-11,13, BIOSCIENCESINFORMATIONSERVICE,14 PHILADELPHIA,PA,US;1989 GIORDANOJETAL:"PERIPHERALLY ADMINISTEREDSEROTONIN5-HT-3RECEPTOR ANTAGONISTSREDUCEINFLAMMATORYPAININ RATS" Databaseaccessionno.PREV199089030180 XP002149140 abstract &EUROPEANJOURNALOFPHARMACOLOGY, vol.170,no.1-2,1989,pages83-86, ISSN:0014-2999 2 2 INTERNATIONALSEARCHREPORTnte,xnal Aoation No PCT/EP00/01269 C.(Contlnuation DOCUMENTS CONSIDERED TO BE RELEVANT CategoryCitationofdocumentwithindication,whereappropnate,oft
herelevantpassagesRelevanttodaimNo. XDATABASEBIOSIS'Online!1-11,13, BIOSCIENCESINFORMATIONSERVICE,14 PHILADELPHIA,PA,US;1989 GIORDANOJETAL:"DIFFERENTIAL ANALGESIC ACTIONSOFSEROTONIN5-HT-3RECEPTOR ANTAGONISTSINTHEMOUSE" Databaseaccessionno.PREV198988019024 XP002149141 abstract &NEUROPHARMACOLOGY, vol.28,no.4,1989,pages423-428, ISSN:0028-3908 XDATABASEBIOSIS'Online!1-11,13, BIOSCIENCESINFORMATIONSERVICE,14 PHILADELPHIA,PA,US;1989 ESCHALIERAETAL:"INFLUENCEOFA SPECIFIC5-HT-3ANTAGONISTON CARRAGEENAN-INDUCEDHYPERALGESIAINRATS" Databaseaccessionno.PREV198987128603 XP002149142 abstract &PAIN, vol.36,no.2,1989,pages249-256, ISSN:0304-3959 EWO0048597A(NOVARTISERFINDVERWALT1-14 GMBH;NOVARTISAG(CH);MUELLERWOLFGANG ()24August2000(2000-08-24) thewholedocument XEP0507637A(ERBAMONTINC)1-11,13, 7October1992(1992-10-07)14 thewholedocument XWO9401095A(SMITHKLINEBEECHAMPLC1-11,13, ;SANGERGARETHJOHN(GB);BANNERSTEPHEN14 ED)20January1994(1994-01-20) thewholedocument XDOAKGJETAL:"FORMALIN-INDUCED 1-11,13, NOCICEPTIVEBEHAVIORANDEDEMA:14 INVOLVEMENTOFMULTIPLEPERIPHERAL 5-HYDROXYTRYPTAMINERECEPTORSUBTYPES" NEUROSCIENCE,US,NEWYORK,NY, vol.80,no.3,1997,pages939-949, XP000886556 ISSN:0306-4522 thewholedocument 2 2 INTERNATIONAL SEARCH REPORT ncer.nai Applicatlon No PCT/EP00/01269 C.(Continuation)DOCUMENTSCONSIDEREDTOBERELEVANT Category oCftation ofdocument,withindication,whereappropriate,oftherelevantpass
agesRelevanttodaimNo. XROSENSTEINDMETAL:"ANTINOCICEPTIVE1-11,13, EFFECTSOFMICRODIALYSISADMINISTRATIONOF14 5-HT1AAND5-HTRECEPTORAGONISTSAND ANTAGONISTSINAMODELOFACUTEARTHRITIS" SOCIETYFORNEUROSCIENCE ABSTRACTS,US,SOCIETYFORNEUROSCIENCE, vol.23,no.23,1997,page1540 XP000886228 ISSN:0190-5295 thewholedocument XCUNNINGHAMDETAL:"OPTIMUMANTI-EMETIC11-14 THERAPYFORCISPLATININDUCEDEMESISOVER REPEATCOURSES:ONDANSETRONPLUS DEXAMETHASONECOMPAREDWITH METOCLOPRAMIDE,DEXAMETHASONEPLUS LORAZEPAM" ANNALSOFONCOLOGY,NL,KLUWER,DORDRECHT, vol.7,no.3,1996,pages277-282, XP000886538 ISSN:0923-7534 thewholedocument XDATABASEBIOSIS'Online!1-11,13, BIOSCIENCESINFORMATIONSERVICE,14 PHILADELPHIA,PA,US;1998 BOTELLAAETAL:"Intracolonicglycerol inducesabdominalcontractionsinrats: Roleof5-HT3receptors." Databaseaccessionno.PREV199900012906 XP002149157 abstract &FUNDAMENTAL&CLINICALPHARMACOLOGY, vol.12,no.6,1998,pages619-623, ISSN:0767-3981 XDATABASEBIOSIS'Online ! 1-11,13, BIOSCIENCESINFORMATIONSERVICE,14 PHILADELPHIA,PA,US;1998 SAMBORSKIWLODZIMIERZETAL:"Newconcept ofpharmacologicaltreatmentof fibromyalgia.Doexisttwosubgroupsof fibromyalgiapatients?" Databaseaccessionno.PREV199800453416 XP002149158 abstract &REUMATOLOGIA(WARSAW), vol.36,no.2,1998,pages144-150, ISSN:0034-6233 2 INTERNATIONALSEARCHREPORT !-----------------j Inte xnal Application No . np... 00/01269 PCT/EP00/01269 PatentdocumentPublicationPatentfamily Publication citedin searchreportdatemember (s)date WO0048597A24-08-2000NONE EP0507637A07-10-1992US5122528A16-06-1992 AU1402092A08-10-1992 CA2063912A06-10-1992 JP6172172A21-06-1994 ZA 9202145 A 27-01-1993ZA 9202145 A 27-01-1993 WO9401095A20-01-1994AU4507693A31-01-1994 EP0650355A03-05-1995 JP7508530T21-09-1995