# US 9,517,265 B2 · Methods for the prevention and/or treatment of memory impairment > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 9,517,265 B2 - Document ID: US9517265B2 - Status: Granted - Kind: B2 - Application number: 13/867,470 - Filed: 2013-04-22 - Published: 2013-11-14 - Granted: 2016-12-13 - Earliest claimed: 2010-10-22 - Assignees: The Governing Council of the University of Toronto - Applicants: The Governing Council of the University of Toronto - Inventors: Beverley A. Orser - Web page: https://patentgrep.com/patent/US9517265B2 ## CPC - A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines} - A61K 31/53: having six-membered rings with three nitrogens as the only ring hetero atoms, e.g. chlorazanil, melamine (melarsoprol A61K31/555 {; with four nitrogen atoms A61K31/495}) - A61K 31/551: having two nitrogen atoms, e.g. dilazep - A61K 31/5517: condensed with five-membered rings having nitrogen as a ring hetero atom, e.g. imidazobenzodiazepines, triazolam - C07K 16/286: {against neuromediator receptors, e.g. serotonin receptor, dopamine receptor} - 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) - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) ## Abstract The present invention relates to methods for the prevention and/or treatment of memory impairment and for improving memory and particularly to methods for the prevention and/or treatment of memory impairment and improving memory comprising administering an agent that decreases activity of a GABAA receptor. The present invention also relates the use of an agent that decreases activity of a GABAA receptor for preventing or treating a memory deficit and for improving memory. ## Claims ### Claim 1 A method for attenuating and/or treating a persistent memory deficit, comprising administering a benzodiazepine site inverse agonist, wherein the memory deficit is induced by inflammation and/or administration of an anesthetic selected from the group consisting of isoflurane, sevoflurane, desflurane, etomidate and propofol. ### Claim 2 (depends on 1) The method of claim 1, wherein the memory deficit is short-term memory loss. ### Claim 3 (depends on 1) The method of claim 1, wherein the memory deficit is long-term memory loss. ### Claim 4 (depends on 1) The method of claim 1, wherein the inverse agonist is selected from the group consisting of L-655,708, MRK-016, Ru493851, α5IA, pyridazines, TB-21007, PWZ-029, and combinations thereof. ### Claim 5 (depends on 4) The method of claim 4, wherein the inverse agonist is selected from the group consisting of L-655,708, MRK-016 and combinations thereof. ### Claim 6 (depends on 1) The method of claim 1, wherein the memory deficit is induced by administration of the anesthetic. ### Claim 7 (depends on 1) The method of claim 1, wherein the memory deficit is induced by inflammation. ### Claim 8 (depends on 1) The method of claim 1, wherein the inverse agonist agent reduces inflammation- and/or surgery-induced increases in IL-1β expression and/or activity. ### Claim 9 (depends on 1) The method of claim 1, where the inverse agonist is administered before the memory deficit is induced. ### Claim 10 (depends on 9) The method of claim 9, wherein the inverse agonist is further administered during and/or after the memory deficit is induced. ### Claim 11 (depends on 1) The method of claim 1, where the inverse agonist is administered while the memory deficit is induced. ### Claim 12 (depends on 1) The method of claim 1, where the inverse agonist is administered after the memory deficit is induced. ### Claim 13 (depends on 12) The method of claim 12, wherein the inverse agonist is further administered before and/or while the memory deficit is being induced. ### Claim 14 (depends on 1) The method of claim 1, wherein the inverse agonist preferentially targets α5GABAA receptors. ### Claim 15 (depends on 1) The method of claim 1, wherein the persistent memory deficit is a memory deficit that persists for 24 hours or more after administration of the anesthetic. ### Claim 16 (depends on 1) The method of claim 1, carried out on an immature subject. ### Claim 17 A method for attenuating a persistent memory deficit induced by an anesthetic in a subject to be treated with the anesthetic, the method comprising administering a benzodiazepine site inverse agonist prior to or with the anesthetic to prevent the anesthesia-induced memory deficit, wherein the subject is at risk for a post-anesthetic cognitive deficit and wherein the anesthetic is selected from the group consisting of isoflurane, sevoflurane, desflurane, etomidate and propofol. ### Claim 18 (depends on 17) The method of claim 17, wherein the subject is being anesthetized for surgery. ### Claim 19 (depends on 17) The method of claim 17, wherein the inverse agonist is administered 30 minutes before the anesthetic. ### Claim 20 (depends on 17) The method of claim 17, wherein the method further comprises administering the inverse agonist after administration of the anesthetic. ### Claim 21 (depends on 20) The method of claim 20, wherein the inverse agonist is administered within 72 hours of the anesthetic. ### Claim 22 (depends on 17) The method of claim 17, wherein the inverse agonist preferentially targets α5GABAA receptors. ### Claim 23 (depends on 17) The method of claim 17, wherein the persistent memory deficit persists for 24 hours or more after administration of the anesthetic. ### Claim 24 (depends on 17) The method of claim 17, wherein the subject is immature. ### Claim 25 A method for treating a persistent memory deficit induced by an anesthetic in a subject having been treated with the anesthetic, the method comprising administering a benzodiazepine site inverse agonist to treat the anesthesia-induced memory deficit, wherein the subject is experiencing a post-anesthetic cognitive deficit and wherein the anesthetic is selected from the group consisting of isoflurane, sevoflurane, desflurane, etomidate and propofol. ### Claim 26 (depends on 25) The method of claim 25, wherein the subject was anesthetized for surgery. ### Claim 27 (depends on 25) The method of claim 25, wherein the inverse agonist is administered within 72 hours of the anesthetic. ### Claim 28 (depends on 25) The method of claim 25, wherein the inverse agonist preferentially targets α5GABAA receptors. ### Claim 29 (depends on 25) The method of claim 25, wherein the persistent memory deficit persists for 24 hours or more after administration of the anesthetic. ### Claim 30 (depends on 25) The method of claim 25, wherein the subject is immature.