Abstract: The present invention is directed to novel tetracyclic heteroatom containing derivatives, pharmaceutical compositions containing them, their use in the treatment of disorders mediated by one or more sex steroid hormone receptors and processes for their preparation.
Abstract: This invention relates to pulsatile dose administration of gossypol or pharmaceutical compositions thereof for treating diseases, disorders and conditions responsive to gossypol, inhibiting the activity of anti-apoptotic Bcl-2 family proteins, inducing apoptosis in cells and increasing the sensitivity of cells to inducers of apoptosis.
Type:
Application
Filed:
December 10, 2009
Publication date:
July 29, 2010
Applicant:
Ascenta Therapeutics, Inc.
Inventors:
Jon T. Holmlund, Mel Sorensen, Lance Leopold, Dajun Yang
Abstract: Indolo[3,2-c]quinoline compounds of formula (I) shown below. Each variable in this formula is defined herein. These compounds can be used to inhibit both growth of cancer cells and activity of telomerase.
Type:
Grant
Filed:
April 9, 2009
Date of Patent:
July 27, 2010
Assignee:
Kaohsiung Medical University
Inventors:
Cherng-Chyi Tzeng, Yeh-Long Chen, Jing-Jer Lin, Chih-Ming Lu
Abstract: The present invention relates to pyrrolidine-2,5-dione compounds, and methods of preparation of these compounds. The present invention also relates to pharmaceutical compositions comprising pyrrolidine-2,5-dione compounds. The present invention provides methods of treating a cell proliferative disorder, such as a cancer, by administering to a subject in need thereof a therapeutically effective amount of a compound or pyrrolidine-2,5-dione compound of the present invention.
Type:
Application
Filed:
June 19, 2008
Publication date:
July 22, 2010
Applicant:
ARQULE, INC.
Inventors:
Neil Westlund, Jason Hill, Mark A. Ashwell, Nivedita Namdev, Jianqiang Wang, Syed Ali
Abstract: Compounds of formula G1-L-G2, where -G1 is a radical structurally close to cryptolepine, -L- is a single covalent bond or a covalent linking biradical selected from (CH2)rNR??(CH2)s and —(CH2)rNR??(CH2)sNR??(CH2)t—, —R?? and —R?? are radicals, same or different, selected from the group consisting of H and (C1-C3)-alkyl; r, s and t are an integer from 1 to 3 and, -G2 is H or a radical structurally close to -G1, are intercalators. They are compounds which intercalate between DNA base pairs, and are useful as therapeutic agents against cancer, as assess by an in vitro test of cytotoxicity with human leukemia cells Jurkat E6-1 and human carcinoma cells GLC-4. Preferred compounds are those where -G1 is bonded to -L- through a carbonyl amino and -L- is —(CH2)3NCH3(CH2)3 or —(CH2)2NCH3(CH2)sNCH3(CH2)2— where s =2 or 3.
Type:
Grant
Filed:
November 18, 2004
Date of Patent:
June 1, 2010
Assignees:
Crystax Pharmaceuticals, Universitat Politecnica de Catalunya, Consejo Superior de Investigactiones Cientificas
Abstract: Compounds of the formula (I), in which R1, R2, R3, R4, R5, and R6 and m have the meanings indicated in Claim 1, can be employed, inter alia, for the treatment of tumours.
Type:
Application
Filed:
February 21, 2008
Publication date:
May 13, 2010
Applicant:
MERCK PATENT GESELLSCHAFT MIT BESCHRANKTER HAFTUNG
Abstract: The compounds of formula (I) wherein R1 to R8 and R11 have the meanings as given in the description, the salts thereof, the N-oxides of the compounds and the salts thereof, and the stereoisomers of the compounds, the salts, the N-oxides of the compounds and the N-oxides of the salts thereof are effective inhibitors of the type 5 phosphodiesterase.
Abstract: Methods of treating diseases caused by cell division or that are treated by inhibiting mitosis by administering two doses of an inhibitor of mitosis between the biologically effective dose and the maximum tolerated dose in a dosing cycle that allows for the recovery or subsiding of side effects, wherein the second dose is administered 24 to 48 hours after the first dose.
Type:
Application
Filed:
October 16, 2009
Publication date:
April 22, 2010
Applicant:
ARRAY BIOPHARMA INC.
Inventors:
Brian J. Tunquist, Duncan H. Walker, Richard D. Woessner
Abstract: Methods of treating, ameliorating, preventing, or reducing the risk of developing an auto-immune disease and/or an inflammatory condition, such as systemic lupus erythematosus, in a patient, such as a human being, using a therapeutically effective amount of an agent(s) that inhibits the activity of one or more of histone deacetylase (HDAC), IKB kinase (IKK-2), nuclear factor kB (NF-kB), ubiquitin/proteasome and Janus kinase (JAK) are disclosed. Compounds useful in such methods are also presented.
Type:
Application
Filed:
May 16, 2008
Publication date:
April 15, 2010
Inventors:
Stephen K. Horrigan, Qin Zong, Daniel Soppet, Juana Castaneda, Bo Chen, Ricardo Cibotti, Laurent P. Audoly, Anthony Coyle, Peter Kiener
Abstract: A compound of formula (I) or a pharmaceutically acceptable salt or prodrug ester thereof: wherein the groups R1, R2, R3, R7 and X are as defined in the specification.
Type:
Application
Filed:
August 28, 2007
Publication date:
March 18, 2010
Inventors:
Laszlo Revesz, Achim Schlapbach, Rudolf Walchli
Abstract: Provided herein are compounds that modulate the activity of a bacterial peptidyl tRNA hydrolase, including compositions and dosage forms comprising the compounds. Further provided herein are methods for screening and identifying compounds that modulate the activity of a bacterial peptidyl tRNA hydrolase. In particular, provided herein are assays for the identification of compounds that inhibit or reduce the activity of a bacterial peptidyl tRNA hydrolase. The methods provided herein provide a simple, sensitive assay for high-throughput screening of libraries of compounds to identify pharmaceutical leads useful for preventing, treating, and managing a bacterial infection or one or more symptoms thereof. Further provided herein are methods for preventing or inhibiting bacterial proliferation as well as methods for preventing, treating, and/or managing a bacterial infection using such compounds and compositions.
Type:
Application
Filed:
September 21, 2007
Publication date:
March 18, 2010
Inventors:
Soongyu Choi, Arthur Branstrom, Scott A. Gothe, Richard Lipman, Tamil Arasu, Richard G. Wilde
Abstract: Heteroarylpyridinone derivatives represented by formula (I) wherein R1, R2, R3, R4, R5, and X are as defined in the specification, compositions thereof, and methods of use thereof. Particularly, there are described isoquinolinoyrrolopyridinones, pharmaceutical compositions comprising them and their use as therapeutic agents in the treatment of cancer and cell proliferation disorders.
Type:
Application
Filed:
February 18, 2008
Publication date:
March 4, 2010
Applicant:
NERVIANO MEDICAL SCIENCES S.R.L.
Inventors:
Ermes Vanotti, Maria Menichincheri, Alessandro Scolaro
Abstract: This invention relates to pharmaceutical compositions and methods where S(?)-nornicotine, R(+)-nornicotine, or racemic nornicotine are co-administered with an opioid analgesic in amounts effective to cause or enhance a synergistic analgesic response to treat pain (including acute, chronic, and cancer related pain). Preferably the coadministration of nornicotine with the opioid results in decreased dependence and tolerance potential as well as diminishing side effects, compared to conventional opioid therapy.
Type:
Application
Filed:
December 11, 2007
Publication date:
February 25, 2010
Applicant:
University of Kentucky Research Foundation
Inventors:
Joseph R. Holtman, JR., Peter A. Crooks
Abstract: The present invention relates to compounds useful for detecting the activity of human aldoketoreductase 1Cs, compounds useful for competitively inhibiting human aldoketoreductase 1Cs and compounds useful for treating human aldoketoreductase 1C-related cancers, as well as pharmaceutical compositions and methods of manufacture thereof.
Type:
Application
Filed:
August 19, 2005
Publication date:
February 25, 2010
Inventors:
Dominic J. Yee, Vojtech Balsanek, Dalibor Sames
Abstract: The following abstract will replace all prior versions of the abstract in the application: The mixture comprises a vanilloid receptor agonist with a substance, which inhibits nerve regeneration. The mixture is suitable for use, especially, as a painkiller.
Abstract: Elastin-like polypeptide (ELP) serves as a vector for thermally-targeted delivery of therapeutics, including cytotoxic chemotherapeutic drugs such as doxorubicin. Examples of an ELP-based delivery vehicle can comprise: (1) a cell penetrating peptide, such as a Tat protein, (2) ELP, and (3) the lysosomally degradable glycylphenylalanylleucylglycine (GFLG) spacer and a cysteine residue conjugated to therapeutic such as doxorubicin, or a analog thereof.
Type:
Application
Filed:
January 29, 2007
Publication date:
January 28, 2010
Inventors:
Drazen Raucher, Gene Bidwell, III, Waldemar Priebe, Izabela Fokt
Abstract: Compositions and methods for treating chronic infectious diseases using substantially pure oxymatrine or pharmaceutically acceptable salts or esters thereof are disclosed. In one embodiment described herein, the chronic infectious disease is chronic fatigue syndrome. Further described are compositions having an anti-infective amount of substantially pure oxymatrine or pharmaceutically acceptable salts or esters thereof.
Abstract: The present invention is a DNA intercalating agent represented by the structure Y-Z-Y, wherein Y is an anti-tumor bis-carbazole and Z is a linear arrangement of multiple aromatic rings, containing at least two aromatic rings, or at least two alicyclic rings, said rings being linked in a 1,4 or 1,3 manner. Methods of inhibiting cancer cells and treating subjects having cancer with these agents are also provided.
Abstract: The present invention relates to Indenoisoquinolinone Analogs, compositions comprising an effective amount of an Indenoisoquinolinone Analog and methods for treating or preventing an inflammatory disease, a reperfusion injury, diabetes mellitus, a diabetic complication, reoxygenation injury resulting from organ transplantation, an ischemic condition, a neurodegenerative disease, renal failure, a vascular disease, a cardiovascular disease, cancer, a complication of prematurity, cardiomyopathy, retinopathy, nephropathy, neuropathy, erectile dysfunction or urinary incontinence, comprising administering to a subject in need thereof an effective amount of an Indenoisoquinolinone Analog.
Type:
Application
Filed:
February 28, 2008
Publication date:
January 7, 2010
Inventors:
Prakash JAGTAP, Duy-Phong PHAM-HUU, Frederick COHEN, Xiaojing WANG
Abstract: The present invention relates to the use of ergot derivatives or ergolines, and in particular of lisuride and terguride for the prophylaxis and treatment of constrictive capillary arteriopathy. Constrictive capillary arteriopathy refers to the diseases pulmonary arterial hypertension, endogenously induced or exogenously induced glomeruloscleroses as well as secondary Raynaud's syndrome.
Type:
Application
Filed:
November 23, 2007
Publication date:
December 31, 2009
Applicant:
ERGONEX PHARMA GMBH
Inventors:
Rudolf Reiter, Johannes Tack, Reinhard Horowski
Abstract: A combination of HKI-272 compound and a vinorelbine compound in the treatment of a neoplasm is provided. Regimens, kits, and methods for treatment of neoplasm, including breast cancer including metastatic breast cancer, and lung cancer, using this combination, optionally in combination with other anti-neoplastic agents, or immune modulators are also described.
Abstract: The present invention provides, in part, compounds and compositions including a thiazole moiety, that may be useful, for example, for treating cancers, for example kidney cancer.
Abstract: Indolo[3,2-c]quinoline compounds of formula (I) shown below. Each variable in this formula is defined herein. These compounds can be used to inhibit both growth of cancer cells and activity of telomerase.
Type:
Application
Filed:
April 9, 2009
Publication date:
December 3, 2009
Applicant:
KAOHSIUNG MEDICAL UNIVERSITY
Inventors:
CHERNG-CHYI TZENG, YEH-LONG CHEN, JING-JER LIN, CHIH-MING LU
Abstract: The invention relates to a method of inhibiting chemotherapy induced upregulation of Cathepsin S on the surface of tumour cells, the method comprising the administration of a Cathepsin S inhibitor to said cells. Also provided is a therapy comprising an anti Cathepsin S antibody, in particular an anti-Cathepsin S antibody which does not inhibit the proteolytic effect of Cathepsin S but nevertheless inhibits angiogenesis and a combination treatment comprising a Cathepsin S inhibitor and a therapeutic agent.
Type:
Application
Filed:
April 10, 2007
Publication date:
October 29, 2009
Applicant:
Fusion Antibodies Limited
Inventors:
Shane Olwill, Christopher Scott, Julie Gormley, Jaquin Thomas, Roberta Burden, Darragh McMeel, James Johnston
Abstract: The embodiments provide compounds of the general Formulae I, II, III, IV, V, VI, VII, and X, as well as compositions, including pharmaceutical compositions, comprising a subject compound. The embodiments further provide treatment methods, including methods of treating a hepatitis C virus infection and methods of treating liver fibrosis, the methods generally involving administering to an individual in need thereof an effective amount of a subject compound or composition.
Type:
Application
Filed:
April 14, 2009
Publication date:
October 29, 2009
Applicant:
InterMune, Inc.
Inventors:
Scott D. Seiwert, Leonid Beigelman, Brad Buckman, Antitsa Dimitrova Stoycheva, Steven B. Porter, Williamson Ziegler Bradford, Vladimir Serebryany
Abstract: Provided herein are compounds that bind to androgen receptors and/or modulate activity of androgen receptors, and to methods for making and using such compounds. Also provided are compositions including such compounds and methods for making and using such compositions.
Type:
Application
Filed:
June 12, 2006
Publication date:
October 22, 2009
Applicant:
LIGAND PHARMACEUTICALS INCORPORATED
Inventors:
Bijan Pedram, Cornelis Arjan Van Oeveren, Lin Zhi, Shuo Zhao, Yixing Shen
Abstract: Systems and methods for treating inflammatory and proliferative diseases, and wounds, using as a pharmacon a UCP and/or Fas antibody or other inhibitor, or combination thereof, and a therapeutically acceptable amount of a fatty acid metabolism inhibitor and/or a therapeutically acceptable amount of a glucose metabolism inhibitor, optionally in combination with one or more chemotherpeutic agents. In preferred embodiments, the invention combines an antibody against UCP and/or Fas antigen with an oxirane carboxylic acid, represented by etomoxir, and/or with a 2-deoxyglucose compound, represented by 2-deoxy-D-glucose. The systems and methods of the invention can be used to treat drug-resistant or multi-drug resistant cancers.
Type:
Application
Filed:
February 23, 2009
Publication date:
October 15, 2009
Applicant:
The Regents of the University of Colorado
Inventors:
M. Karen Newell, Evan Newell, Elizabeth Villalobos-Menuey
Abstract: A compound of formula I, wherein X, Z, R1 to R10, R15, R16, m, n, r and t are as defined in claim 1, or a pharmaceutically acceptable salt or ester thereof, useful as an alpha-2 antagonist. The compounds of formula I can be used for the treatment of diseases or conditions where antagonists of alpha-2 adrenoceptors are indicated to be effective.
Type:
Grant
Filed:
April 3, 2003
Date of Patent:
September 22, 2009
Assignee:
Orion Corporation
Inventors:
David Din Belle, Reija Jokela, Arto Tolvanen, Antti Haapalinna, Arto Karjalainen, Jukka Sallinen, Jari Ratilainen
Abstract: Indole alkaloid derivatives having an opioid receptor agonistic effect, their synthesis, and therapeutic compositions containing these derivatives, and methods of treating conditions with these compounds and therapeutic compositions, are provided.
Abstract: Provided herein are compounds that bind to androgen receptors and/or modulate activity of androgen receptors and/or modulate the amount of androgen receptors; and to methods for making and using such compounds. Also provided are compositions containing such compounds and methods for making and using such compositions.
Type:
Application
Filed:
December 21, 2006
Publication date:
August 13, 2009
Inventors:
Cornelis Arjan Van Oeveren, Yixing Shen, Shuo Zhao, Lin Zhi
Abstract: The invention relates to the use of 9-hydroxy ellipticine derivatives for the treatment of cancer. 9-hydroxy ellipticine derivatives may prove particularly useful for the treatment of metastatic cancers or cancers escaping conventional cytotoxic chemotherapies.
Type:
Application
Filed:
May 21, 2007
Publication date:
August 6, 2009
Inventors:
Christian Auclair, Valerie Polard, Andrei Maksimenko
Abstract: A method of inhibiting viral infection in a mammal in need of same, includes administering an effective amount of at least one of the compounds of FGI-103 which are represented by 273, 365 and 510 either prophylactically to prevent viral infection, or therapeutically following viral infection. These compounds appear to selectively inhibit Caspase 8 as a method of preventing infective viral particle release. They can be administered IV, IP, orally or via other conventional administration routes. The compounds are highly effective, requiring relatively low dosages on the order of 1 ng/kg-200 mg/kg of body weight.
Abstract: The present invention provides methods of treating of disorders characterized by defective mitochondrial activity. In particular compounds of the present invention can be used in the treatment metabolic diseases and neurodegenerative diseases. The methods are also useful to increase oxidative phosphorylation or to decrease reactive oxygen species (ROS) production in a subject in need thereof.
Abstract: Bis- and tris-dihydroxyaryl compounds and their methylenedioxy analogs and pharmaceutically acceptable esters, pharmaceutical compositions containing them, and their use in the treatment of amyloid diseases, especially A? amyloidosis, such as observed in Alzheimer's disease, use in the reduction of A? peptide in vivo, use in modulating APP processing, and use in modulating the activity of APP secretase.
Abstract: The invention discloses novel sulfur-containing naphthalimide derivatives, and the preparation and uses thereof. The conjugated plane of naphthalimide derivatives of the invention is enlarged by incorporating 5-or 6-membered heteroaromatic ring and/or introducing S heteroatom, thus increasing the anti-tumor activity of naphthalimide. The compounds of the invention displays significant inhibiting activities to the proliferation of various tumor cells such as human lung cancer, gastric cancer, liver cancer, leucocythemia and the like. The inhibition of cell proliferation is dose-dependent.
Type:
Grant
Filed:
October 31, 2005
Date of Patent:
June 2, 2009
Assignees:
East China University of Science and Technology, Shanghai Institute of Materia Medica, Chinese Academy of Science, Dalian University of Technology
Abstract: Provided herein are methods for identifying a subject afflicted with chronic lymphocytic leukemia who is responsive to treatment with a chemotherapeutic agent by detecting the presence or absence of at least one APOE4 allele in the subject, the presence of an APOE4 allele identifying the subject as responsive to the treatment. Also provided are methods of treating a subject afflicted with chronic lymphocytic leukemia, including administering an estrogenic agent, an androgen withdrawal agent, an apoE4 peptide or mimetic thereof, and/or a chemotherapeutic agent in an amount effective to treat said chronic lymphocytic leukemia. Methods of determining a prognosis for a patient diagnosed with chronic lymphocytic leukemia are also provided. In addition, methods for stratifying a subject into a subgroup of a clinical trial and methods for identifying a patient in a clinical trial of a treatment for chronic lymphocytic leukemia are herein provided.
Type:
Application
Filed:
November 5, 2008
Publication date:
May 28, 2009
Applicant:
Duke University
Inventors:
J. Brice Weinberg, Warren J. Strittmatter
Abstract: The use of an arylidene 2-indolinone derivative for treating tumors involving Met, PDGF-R, FGF-RI, FGF-R3 or Kit tyrosine kinases, or a Ret oncoprotein which includes a MEN2-associated mutation is disclosed.
Type:
Application
Filed:
November 13, 2008
Publication date:
May 21, 2009
Applicants:
Cell Therapeutics, Inc., Instituto Nazionale per lo Studio e la Cura dei Tumori
Inventors:
Cinzia Lanzi, Giuliana Cassinelli, Giuditta Cuccuru, Marco A. Pierotti, Franco Zunino, Ernesto Menta
Abstract: Methods and compositions are provided for treating cancer, the methods including the step administering, either sequentially or simultaneously, (i) a compound of the xanthenone acetic acid group of compounds, and (ii) at least one compound selected from compounds which modulate TNF production and compounds which act on biochemical pathways leading to TNF synthesis. Compositions include a combination of (i) and (ii) above, together with acceptable pharmaceutical carriers and/or vehicles.
Type:
Grant
Filed:
January 14, 2003
Date of Patent:
March 31, 2009
Assignee:
Cancer Research Technology Limited
Inventors:
Bruce Charles Baguley, Lai-Ming Ching, Martin Philpott
Abstract: The present invention relates to derivatives of 4-(Thio- or Selenoxanthene-9-ylidene)-piperidine or acridine and pharmaceutically acceptable salts thereof, use of these compounds as a medicament and for the manufacture of a medicament for treatment of a disease state which can be alleviated by treatment with a 5-HT2B antagonist.
Type:
Grant
Filed:
April 19, 2006
Date of Patent:
March 31, 2009
Assignee:
Biofrontera Bioscience GmbH
Inventors:
Hermann Lubbert, Christoph Ullmer, Emile Bellott, Mark Froimowitz, Douglas Gordon
Abstract: Compounds from 14 Kenyan plants, including from the root of Dovyalis abyssinica and Clutia robusta have been characterized and isolated, and their uses are disclosed.
Type:
Application
Filed:
September 6, 2007
Publication date:
March 12, 2009
Inventors:
Paul Kiprono Chepkwony, Maria Medina, Mitchell Medina
Abstract: The present invention generally relates to a series of compounds, to pharmaceutical compositions containing the compounds, and to use of the compounds and compositions as therapeutic agents. More specifically, compounds of the present invention are hexahydroazepinoindole and octahydroazepinoindole compounds. These compounds are serotonin receptor (5-HT) ligands and are useful for treating diseases, disorders, and conditions wherein modulation of the activity of serotonin receptors (5-HT) is desired (e.g. anxiety, depression and obesity).
Type:
Application
Filed:
August 5, 2008
Publication date:
March 12, 2009
Inventors:
Youssef L. Bennani, David C. Bom, Michael J. Robarge
Abstract: The present invention overcomes limitations of the prior art by providing new compounds and methods for the treatment of conditions, such as neurodegenerative diseases (e.g., multiple sclerosis), psychiatric disorders (e.g., psychosis, bipolar disorder, depression, neuropathic pain), conditions involving CNS-mediated chronic pain, spinal cord injuries, and other diseases or injuries.
Type:
Application
Filed:
May 5, 2008
Publication date:
March 5, 2009
Applicant:
Reata Pharmaceuticals, Inc.
Inventors:
Michael B. Sporn, Karen T. Liby, Gordon W. Gribble, Tadashi Honda, John Letterio
Abstract: This invention provides methods for treating neoplasias in a mammal. In particular, the invention provides methods for treating various types of lymphomas, including relapsed forms of non-Hodgkin's Lymphoma. These methods involve the administration of liposome-encapsulated vinca alkaloids, e.g., vincristine, to a mammal with a lymphoma.
Type:
Application
Filed:
March 7, 2008
Publication date:
February 12, 2009
Applicants:
Inex Pharmaceuticals Corporation, Board of Regents, The University of Texas System
Inventors:
Andreas SARRIS, Fermando CABANILLAS, Patricia M. LOGAN, Clive T.R. BURGE, James H. GOLDIE, Murray S. WEBB
Abstract: This application relates to novel fused tricyclic thienopyridines of Formulas I and II, which useful for treating Hepatitis B infection and other diseases. This application also relates to pharmaceutical compositions comprising thienopyridines and to the use of such compositions to treat Hepatitis B and other diseases.
Type:
Application
Filed:
January 3, 2008
Publication date:
January 29, 2009
Applicant:
Valeant Research & Development
Inventors:
Huanming Chen, Robert Tam, Anneke K. Raney
Abstract: Provided herein are compounds that bind to androgen receptors and/or modulate activity of androgen receptors, and to methods for making and using such compounds. Also provided are compositions including such compounds and methods for making and using such compositions.
Type:
Application
Filed:
June 12, 2006
Publication date:
January 29, 2009
Applicant:
LIGAND PHARMACEUTICALS INCORPORATED
Inventors:
Bijan Pedram, Cornelis Arjan Van Oeveren, Lin Zhi, Shuo Zhao, Yixing Shen
Abstract: Optionally substituted chromenoisoquinolines and analogs and derivatives thereof are described herein. In addition, syntheses of these compounds are described herein. In addition, uses of these compounds as dopamine receptor binding compounds are described herein.
Abstract: In its many embodiments, the present invention provides tetracyclic compounds of formula I or formula II (wherein the various moieties are as defined herein) useful as metabotropic glutamate receptor (mGluR) antagonists, particularly as selective metabotropic glutamate receptor 1 antagonists, pharmaceutical compositions containing the compounds, and methods of treatment using the compounds and compositions to treat diseases associated with metabotropic glutamate receptor (e.g., mGluR1) such as, for example, pain, migraine, anxiety, urinary incontinence and neurodegenerative diseases such Alzheimers disease.