# US 11,439,624 B2 · Promoting sleep using AT1 receptor blockers > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 11,439,624 B2 - Document ID: US11439624B2 - Status: Granted - Kind: B2 - Application number: 17/027,006 - Filed: 2020-09-21 - Published: 2021-01-14 - Granted: 2022-09-13 - Earliest claimed: 2012-02-07 - Assignees: University of Pittsburgh—Of the Commonwealth System of Higher Education - Applicants: University of Pittsburgh—of the Commonwealth System of Higher Education - Inventors: Georgina Cano; Alan F. Sved - Web page: https://patentgrep.com/patent/US11439624B2 ## CPC - A61K 31/4245: Oxadiazoles - A61K 31/41: having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole - A61K 31/4178: not condensed 1,3-diazoles and containing further heterocyclic rings, e.g. pilocarpine, nitrofurantoin - A61K 31/4184: condensed with carbocyclic rings, e.g. benzimidazoles - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61P 25/00: Drugs for disorders of the nervous system - A61P 25/20: Hypnotics; Sedatives - 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 ## Abstract The present invention relates to the use of an Angiotensin II type 1 (AT1) receptor blocker for promoting sleep and/or the treatment of insomnia. It is based, at least in part, on the results of experiments performed using a validated rat model of stress-induced insomnia in which candesartan was found to ameliorate sleep disturbances induced by stress. Further, it was observed that this effect seems to be caused by blockade of AT1 receptors located in several brain regions that are key components of the neural circuitry activated during insomnia. In contrast to currently marketed treatments for insomnia, the AT1 receptor blocker was found to restore normal sleep without inhibiting REM sleep and/or inducing atypical wave components in the EEG. ## Claims ### Claim 1 A method for treating primary insomnia in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of at least one AT1 receptor blocker that promotes sleep, wherein the therapeutically effective amount is at least about 50% lower than a dosage of the AT1 receptor blocker for treating hypertension, wherein the AT1 receptor blocker is selected from the group consisting of azilsartan, candesartan, and combinations thereof. ### Claim 2 (depends on 1) The method of claim 1, wherein the AT1 receptor blocker is azilsartan. ### Claim 3 (depends on 1) The method of claim 1, wherein the AT1 receptor blocker is candesartan. ### Claim 4 (depends on 1) The method of claim 1, wherein the AT1 receptor blocker is a combination of azilsartan and candesartan. ### Claim 5 (depends on 1) The method of claim 1, further comprising administering to the subject a second sleep-promoting agent. ### Claim 6 (depends on 5) The method of claim 5, wherein the second sleep-promoting agent is an H1 antagonist. ### Claim 7 (depends on 6) The method of claim 6, wherein the H1 antagonist is selected from the group consisting of diphenhydramine hydrochloride, doxepin, doxylamine succinate, orphenadrine, bromodiphenhydramine, and dimenhydrinate. ### Claim 8 (depends on 5) The method of claim 5, wherein the second sleep-promoting agent is selected from the group consisting of an H3 agonist, immepip, imetit, methimepip, immethridine, R-alpha-methylhistamine, 4-benzyl-1H-imidazole-based H3 receptor agonist, and H3B agonist. ### Claim 9 (depends on 5) The method of claim 5, wherein the second sleep-promoting agent is a GABAA ligand with alpha-3 or alpha-2/alpha-3 agonist activity. ### Claim 10 (depends on 5) The method of claim 5, wherein the second sleep-promoting agent is selected from the group consisting of zolpidem, zaleplon, and eszopiclone. ### Claim 11 (depends on 5) The method of claim 5, wherein the second sleep-promoting agent is a benzodiazepine. ### Claim 12 (depends on 11) The method of claim 11, wherein the benzodiazepine is selected from the group consisting of diazepam, clonazepam, lorazepam, and alprazolam. ### Claim 13 (depends on 5) The method of claim 5, wherein the second sleep-promoting agent is a corticotropin releasing hormone antagonist. ### Claim 14 (depends on 5) The method of claim 5, wherein the second sleep-promoting agent is a melatonin receptor agonist. ### Claim 15 (depends on 14) The method of claim 14, wherein the melatonin receptor agonist is selected from the group consisting of ramelteon, agomelatine, tasimelteon, TIK-301, and melatonin. ### Claim 16 (depends on 14) The method of claim 14, wherein the melatonin receptor agonist is administered to the subject in a therapeutically effective amount that is lower than a dosage of the melatonin receptor agonist when the melatonin receptor agonist is the only sleep-promoting agent administered to the subject. ### Claim 17 (depends on 1) The method of claim 1, further comprising administering to the subject a homeopathic sleep aid. ### Claim 18 (depends on 17) The method of claim 17, wherein the homeopathic sleep aid is selected from the group consisting of tryptophan, L-tryptophan, lavender, chamomile, valerian root, passionflower, lemon balm, inositol, magnesium, humulus lupus, hops extract, St. John's wort, and melatonin. ### Claim 19 (depends on 1) The method of claim 1, wherein the method promotes sleep in the subject through at least one of: decreasing sleep latency, increasing non-rapid eye movement (NREM) sleep, increasing rapid eye movement (REM) sleep, and not inducing atypical wave components in electroencephalogram (EEG).