# US 2019/0167653 A1 · Materials and methods for diagnosis, prevention and/or treatment of stress disorders and conditions associated with a-beta peptide aggregation > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2019/0167653 A1 - Document ID: US20190167653A1 - Status: Published application - Kind: A1 - Application number: 16/267,301 - Filed: 2019-02-04 - Published: 2019-06-06 - Earliest claimed: 2008-09-24 - Assignees: The United States Government as represented by the Department of Veterans Affairs; University of South Florida - Applicants: United States Government as represented by the Department of Veterans Affairs; University of South Florida - Inventors: Valentina Echeverria Moran - Web page: https://patentgrep.com/patent/US20190167653A1 ## CPC - A61K 31/4439: containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole (nicotine A61K31/465) - A61K 51/0455: {having six-membered rings with one nitrogen as the only ring hetero atom} - A61P 25/26: Psychostimulants, e.g. nicotine, cocaine - A61P 25/28: for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia - C07D 401/04: directly linked by a ring-member-to-ring-member bond - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS - C07D: HETEROCYCLIC COMPOUNDS (macromolecular compounds C08) ## Abstract The subject invention concerns materials and methods for treating and/or preventing diseases associated with accumulation of Aβ peptide in neural tissue. The subject invention also concerns materials and methods for treating and/or preventing stress disorders, such as post-traumatic stress disorder (PTSD). In one embodiment, a method of the invention comprises administering a therapeutically effective amount of cotinine, or a pharmaceutically acceptable salt thereof, to a person or animal in need of treatment. The methods of the invention can be used to prevent and/or treat Alzheimer's disease, Parkinson's disease, and/or Down's syndrome. The subject invention also concerns compositions that comprise cotinine, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier, diluent or adjuvant. The subject invention concerns materials and methods for detecting and diagnosing conditions associated with accumulation of Aβ peptide in neural tissue, such as Alzheimer's disease and Parkinson's disease, using the chemical cotinine. In one embodiment, the method comprises administering cotinine labeled with a detectable label to a person or animal. The presence of labeled cotinine in neural tissue is then determined. The level and/or location of cotinine can be analyzed and a diagnosis made. The subject invention also concerns cotinine labeled with a detectable label. In one embodiment, the cotinine is labeled with a radioisotope that can be detected by Positron Emission Tomography (PET) or single photon emission computed tomography (SPECT). ## Claims ### Claim 1 A method for treating and/or preventing a disease or condition associated with the accumulation and/or aggregation of Aβ peptide in neural tissue, or for treating and/or preventing a disorder or condition associated with Down's syndrome, or for treating and/or preventing a post-traumatic stress disorder or condition, said method comprising administering an effective amount of cotinine, or a composition comprising cotinine, or an isomer or racemate thereof, or a pharmaceutically acceptable salt thereof, to a person or animal so as to treat and/or prevent a disease or condition associated with the accumulation and/or aggregation of Aβ peptide in neural tissue, treat and/or prevent a disorder or condition associated with Down's syndrome, or treat and/or prevent a post-traumatic stress disorder or condition, wherein cotinine inhibits formation of soluble Aβ oligomer from Aβ monomers and protects neuron from Aβ toxicity associated with soluble Aβ oligomer and/or enhances the extinction of fear memory in a person or animal in need of treatment. ### Claim 2 (depends on 1) The method according to claim 1, wherein said method further comprises administering one or more drugs for the treatment or prevent of a neurodegenerative condition. ### Claim 3 (depends on 2) The method according to claim 2, wherein said one or more drug is donepezil (ARICEPT), galantamine (RAZADYNE), rivastigmine (EXELON), memantine (AKATINOL), rasagiline (AZILECT), selegiline (ELDEPRYL), L-dopa (LEVODOPA, SINEMET, PARCOPA, STALEVO, MADOPAR), carbidopa (LODOSYN), or benserazide, or an isomer or analog thereof, or a pharmaceutically acceptable salt thereof. ### Claim 4 (depends on 1) The method according to claim 1, wherein said method further comprises administering one or more drugs for the treatment of a stress disorder or condition. ### Claim 5 (depends on 4) The method according to claim 4, wherein said one or more drug is a selective serotonin reuptake inhibitor (SSRI); a serotonin-norepinephrine reuptake inhibitor (SNRI); a tricyclic antidepressants (TCA); 3,4-methylenedioxy-N-methylamphetamine (MDMA); propranolol; clonidine; or ziprasidone. ### Claim 6 (depends on 5) The method according to claim 5, wherein said SSRI is citalopram, escitalopram, fluvoxamine, paroxetine, or sertraline and/or said SNRI is venlafaxine, desvenlafaxine, duloxetine, sibutramine, or milnacripran. ### Claim 7 A method for inhibiting or preventing Aβ oligomerization, or for increasing activity or expression of dopamine- and cyclic AMP-regulated phosphoprotein of 32 kDa (DARPP-32) and/or facilitating serotonin release in neural tissue or a cell, said method comprising contacting a cell with an effective amount of cotinine, or a composition comprising cotinine, or a pharmaceutically acceptable salt thereof; wherein cotinine inhibits formation of soluble Aβ oligomer from Aβ monomers and protects neuron from Aβ toxicity associated with soluble Aβ oligomer and/or increases activity or expression of donamine- and cyclic AMP-regulated phosphoprotein of 32 kDa (DARPP-32) and/or facilitates serotonin release in neural tissue or a cell. ### Claim 8 (depends on 7) The method according to claim 7, wherein said cell is a cortical cell. ### Claim at position 9 9-24. (canceled) ### Claim 25 (depends on 1) The method according to claim 1, wherein interaction of cotinine with Aβ peptide comprises cotinine interacting with residues His-6, Tyr-10, and His-14 of Aβ peptide, ### Claim 26 (depends on 25) The method according to claim 25, wherein pyridine ring of cotinine is positioned between imidazole ring of His-6 and phenyl ring of Tyr-10 of Aβ peptide so as to permit strong π-π interactions and/or wherein methyl group of methylpyrrolidone ring of cotinine is positioned against imidazole ring of His-14 of Aβ peptide so as to permit C—H-π interaction. ### Claim 27 (depends on 1) The method according to claim 1, wherein the Aβ peptide is or comprises Aβ(1-42) peptide.