WO1996006601B1 - Use of 5-ht ligands as anti-pruritic agents - Google Patents
Use of 5-ht ligands as anti-pruritic agentsInfo
- Publication number
- WO1996006601B1 WO1996006601B1 PCT/US1995/010838 US9510838W WO9606601B1 WO 1996006601 B1 WO1996006601 B1 WO 1996006601B1 US 9510838 W US9510838 W US 9510838W WO 9606601 B1 WO9606601 B1 WO 9606601B1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- ligand
- antagonist
- agonist
- agonists
- group
- Prior art date
Links
- 239000003446 ligand Substances 0.000 title claims abstract 16
- 239000003908 antipruritic agent Substances 0.000 title 1
- 238000000034 method Methods 0.000 claims abstract 15
- 208000003251 Pruritus Diseases 0.000 claims abstract 8
- 239000005557 antagonist Substances 0.000 claims abstract 5
- 239000000952 serotonin receptor agonist Substances 0.000 claims abstract 4
- 241000124008 Mammalia Species 0.000 claims abstract 3
- 239000000387 serotonin 5-HT4 receptor agonist Substances 0.000 claims abstract 3
- 150000002148 esters Chemical class 0.000 claims 4
- 150000003839 salts Chemical class 0.000 claims 4
- 239000002484 serotonin 2C antagonist Substances 0.000 claims 4
- HTEVMLYDEWVIQE-SPIKMXEPSA-N 4-(4-methylpiperazin-1-yl)-7-(trifluoromethyl)pyrrolo[1,2-a]quinoxaline dimaleate Chemical compound [H+].[H+].[H+].[H+].[O-]C(=O)\C=C/C([O-])=O.[O-]C(=O)\C=C/C([O-])=O.C1CN(C)CCN1C1=NC2=CC(C(F)(F)F)=CC=C2N2C1=CC=C2 HTEVMLYDEWVIQE-SPIKMXEPSA-N 0.000 claims 2
- ASXGJMSKWNBENU-UHFFFAOYSA-N 8-OH-DPAT Chemical compound C1=CC(O)=C2CC(N(CCC)CCC)CCC2=C1 ASXGJMSKWNBENU-UHFFFAOYSA-N 0.000 claims 2
- 239000000556 agonist Substances 0.000 claims 2
- FPCCSQOGAWCVBH-UHFFFAOYSA-N ketanserin Chemical compound C1=CC(F)=CC=C1C(=O)C1CCN(CCN2C(C3=CC=CC=C3NC2=O)=O)CC1 FPCCSQOGAWCVBH-UHFFFAOYSA-N 0.000 claims 2
- 229960005417 ketanserin Drugs 0.000 claims 2
- XRXDAJYKGWNHTQ-UHFFFAOYSA-N quipazine Chemical compound C1CNCCN1C1=CC=C(C=CC=C2)C2=N1 XRXDAJYKGWNHTQ-UHFFFAOYSA-N 0.000 claims 2
- 229950002315 quipazine Drugs 0.000 claims 2
- WYWNEDARFVJQSG-UHFFFAOYSA-N 2-methylserotonin Chemical compound C1=C(O)C=C2C(CCN)=C(C)NC2=C1 WYWNEDARFVJQSG-UHFFFAOYSA-N 0.000 claims 1
- 206010010744 Conjunctivitis allergic Diseases 0.000 claims 1
- 208000002205 allergic conjunctivitis Diseases 0.000 claims 1
- 208000024998 atopic conjunctivitis Diseases 0.000 claims 1
- -1 spirotraxine Chemical compound 0.000 claims 1
- BYQQRDWZLNYPPA-UHFFFAOYSA-N α-methylserotonin Chemical compound C1=CC(O)=C[C]2C(CC(N)C)=CN=C21 BYQQRDWZLNYPPA-UHFFFAOYSA-N 0.000 claims 1
- 108091032151 5-hydroxytryptamine receptor family Proteins 0.000 abstract 2
- 102000014630 G protein-coupled serotonin receptor activity proteins Human genes 0.000 abstract 2
- 239000003420 antiserotonin agent Substances 0.000 abstract 2
- 230000002009 allergenic effect Effects 0.000 abstract 1
- 239000000427 antigen Substances 0.000 abstract 1
- 102000036639 antigens Human genes 0.000 abstract 1
- 108091007433 antigens Proteins 0.000 abstract 1
- 150000001875 compounds Chemical class 0.000 abstract 1
- 239000004031 partial agonist Substances 0.000 abstract 1
- 239000003521 serotonin 5-HT1 receptor agonist Substances 0.000 abstract 1
- 239000003478 serotonin 5-HT2 receptor agonist Substances 0.000 abstract 1
- 239000000198 serotonin 5-HT3 receptor agonist Substances 0.000 abstract 1
- 238000007910 systemic administration Methods 0.000 abstract 1
Abstract
The present invention is based on the finding that 5-HT receptor ligands are useful in treating experimental models of clinically encountered pruritus (itch). A 5-HT ligand as used in this specification is a compound capable of binding with some selectivity to one or more of 5-HT receptor sites. Systemic administration of 5-HT agonists and antagonists causes a reduction in the number of itch-scratch responses to an ocular challenge by allergenic antigens. Therefore, the present invention relates to a method for treating pruritus by administering systemically a therapeutically effective amount of a 5-HT agonist or antagonist to a mammal afflicted with pruritus. The 5-HT ligands may, for example, be selected from the group consisting of 5-HT1, 5-HT2, 5-HT3, and 5-HT4 agonists, partial agonists and antagonists.
Claims
AMENDED CLAIMS
[received by the International Bureau on 20 February 1996 (20.02.96); original claims 3, 6, 7, 13, 16 and 17 cancelled; new claims 1, 9, 11, 12, 14, 15 and 18-20 added;
remaining claims unchanged; all claims renumbered 1-20 (2 pages)]
HT1 and 2 antagonists and all subtypes thereof, and a pharmaceutically acceptable salt or ester thereof.
12. The method of claim 11, wherein said 5-HT ligand is a 5-HT agonist.
14. The method of claim 11, wherein said 5-HT ligand is a 5- HT1A, 1B, or 1D antagonist. 15. The method of claim. 11, wherein said 5-HT ligand is a 5-
HT2, or 5-HT2C antagonist
15. The method of claim 11, wherein said 5-HT ligand is a 5- HT4 agonist.
19. The method of claim 11m wherein said 5-HT iigand is selected from the group consisting of a-methylserotonin, spirotraxine, ketanserin, quipazine. 2-methylserotononin, 8-OH-DPAT and CGS 12066B.
20. The method of claim 11, wherein said 5-HT ligand or salt or ester is administered orally.
1. A method for treating pruritis which comprises
administering a therapeutically effective amount of a 5-HT ligand selected from the group consisting of 5-HT1, 2, 3 and 4 agonists and all subtypes thereof, 5-HT1 and 2 antagonist and all subtypes thereof, and a pharmaceutically acceptable salt or ester thereof, to a mammal afflicted with pruritis.
2. The method of claim 1, wherein said 5-HT ligand is a 5-HT agonist. 4. The method of claim 1, wherein said 5-HT ligand is a 5-HT-
1A, 1B, or 1D antagonist.
5. The method of claim 1, wherein said 5-HT is a 5-HT2, or 5- HT2C antagonist.
8. The method of claim 1, wherein said 5-HT ligand is a 5-HT4 agonist.
9. The method of claim 1, wherein said 5-HT ligand is selected from the group consisting of α-methylserotonin, spirotraxine, ketanserin, quipazine, 2-methylserotonin, 8-OH-DPAT and CGS 12066B.
10. The method of claim 1 wherein said 5-HT ligand or salt or ester is administered orally.
11. A method of treating pruritus in a mammal afflicted with allergic conjunctivitis which comprises administering systemically a therapeutically effective amount of a 5-HT ligand selected from the group consisting of 5-HT1, 2, 3 arid 4 agonists and all subtypes thereof, 5-
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US08/298,245 US5521183A (en) | 1994-08-30 | 1994-08-30 | Use of 5-HT ligands as anti-pruritic agents |
| US08/298,245 | 1994-08-30 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| WO1996006601A1 WO1996006601A1 (en) | 1996-03-07 |
| WO1996006601B1 true WO1996006601B1 (en) | 1996-03-21 |
Family
ID=23149684
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/US1995/010838 WO1996006601A1 (en) | 1994-08-30 | 1995-08-25 | Use of 5-ht ligands as anti-pruritic agents |
Country Status (2)
| Country | Link |
|---|---|
| US (1) | US5521183A (en) |
| WO (1) | WO1996006601A1 (en) |
Families Citing this family (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BR9708146A (en) * | 1996-03-15 | 1999-07-27 | Lilly Co Eli | Treatment process for common cold or allergic rhinitis |
| US5869497A (en) * | 1996-03-15 | 1999-02-09 | Eli Lilly And Company | Method of treating or ameliorating the symptoms of common cold or allergic rhinitis |
| US5886003A (en) * | 1996-03-25 | 1999-03-23 | Eli Lilly And Company | Methods of treating or ameliorating the symptoms of venomous bites and stings |
| FR2758263B1 (en) * | 1997-01-16 | 1999-12-17 | Oreal | USE OF AN ANTAGONIST OR AN AGONIST OF SEROTONIN RESPECTIVELY OF THE RECEPTOR 5HT2 AND 5HT1D IN A COSMETIC OR DERMATOLOGICAL COMPOSITION FOR SENSITIVE SKINS AND COMPOSITION OBTAINED |
| CA2391497C (en) * | 1999-11-23 | 2008-12-30 | Janssen Pharmaceutica N.V. | Use of 5ht3 agonists for relaxing the fundus |
| BR0109193A (en) * | 2000-03-17 | 2003-05-27 | Alcon Inc | 5-ht2 and 5-ht1a agonist activity compounds for treatment of glaucoma |
| WO2008086069A1 (en) * | 2007-01-03 | 2008-07-17 | The General Hospital Corporation | Methods of treating itch |
| US9044510B2 (en) * | 2007-11-01 | 2015-06-02 | Washington University | Compositions and methods for treating pruritus |
| US20100048607A1 (en) * | 2008-08-25 | 2010-02-25 | Chandrashekhar Kocherlakota | Formulations comprising palonosetron |
| US8957024B2 (en) | 2011-07-27 | 2015-02-17 | Washington University | Composition and methods for reducing opioid-induced pruritus |
| WO2013154513A1 (en) | 2012-04-04 | 2013-10-17 | Mi̇lli̇ Savunma Bakanliği | The use of 5-ht7 receptor antagonists including some atypical antipsychotics as antipruritic agents |
| US8906951B1 (en) | 2013-06-24 | 2014-12-09 | Tigercat Pharma, Inc. | Use of NK-1 receptor antagonists in pruritus |
| US9198898B2 (en) | 2013-06-24 | 2015-12-01 | Tigercat Pharma, Inc. | Use of NK-1 receptor antagonists in pruritus |
| WO2016118632A1 (en) | 2015-01-20 | 2016-07-28 | The General Hospital Corporation | Prevention and treatment of itch with an mrgpr antagonist |
| CA3033534A1 (en) * | 2016-08-23 | 2018-03-01 | Neurim Pharmaceuticals Ltd. | Method for treating pruritus and/or itch |
Family Cites Families (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4839374A (en) * | 1984-01-09 | 1989-06-13 | Janssen Pharmaceutica, N.V. | 4-((Bicyclic heterocyclyl)-methyl and -hetero)-piperidines |
| PH23995A (en) * | 1984-01-09 | 1990-02-09 | Janssen Pharmaceutica Nv | 4((bicycle heterocyclyl)-methyl and hetero)piperidines |
| GB8515934D0 (en) * | 1985-06-24 | 1985-07-24 | Janssen Pharmaceutica Nv | (4-piperidinomethyl and-hetero)purines |
| FR2605008B1 (en) * | 1986-10-08 | 1988-12-02 | Synthelabo | IMIDAZO (4,5-B) PYRIDINONE-2 DERIVATIVES, THEIR PREPARATION AND THEIR THERAPEUTIC APPLICATION |
| US5071846A (en) * | 1987-07-01 | 1991-12-10 | Janssen Pharmaceutica N.V. | Anti-hystaminic [(bicyclic heterocyclyl) methyl and --hetero] substituted hexahydro-1H-azepines and pyrrolidines |
| US5151424A (en) * | 1987-07-01 | 1992-09-29 | Janssen Pharmaceutica N.V. | Pharmacologically active (Bicyclic heterocyclyl)methyl and -hetero) substituted hexahydro-1H-azepines and pyrrolidines |
| GB8900380D0 (en) * | 1989-01-09 | 1989-03-08 | Janssen Pharmaceutica Nv | 2-aminopyrimidinone derivatives |
| PH30434A (en) * | 1989-04-07 | 1997-05-09 | Janssen Pharmaceutica Nv | Hydroxyalkylfuranyl derivatives |
| EP0690715B1 (en) * | 1993-03-26 | 2003-05-28 | Beth Israel Hospital Association | Topical and systemic application of buspirone or derivatives thereof for treatment of pathological conditions associated with immune responses |
| WO1995009167A1 (en) * | 1993-09-30 | 1995-04-06 | Tokyo Tanabe Company Limited | Indoline derivative and 5-ht3 receptor antagonist containing the same as active ingredient |
-
1994
- 1994-08-30 US US08/298,245 patent/US5521183A/en not_active Expired - Fee Related
-
1995
- 1995-08-25 WO PCT/US1995/010838 patent/WO1996006601A1/en active Application Filing
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