# US 10,117,868 B2 · Systems pharmacology for treating ocular disorders > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,117,868 B2 - Document ID: US10117868B2 - Status: Granted - Kind: B2 - Application number: 15/487,963 - Filed: 2017-04-14 - Published: 2018-03-15 - Granted: 2018-11-06 - Earliest claimed: 2016-04-14 - Assignees: Case Western Reserve University - Applicants: Case Western Reserve University - Inventors: Krzysztof Palczewski; Yu Chen; Akiko Maeda - Web page: https://patentgrep.com/patent/US10117868B2 ## CPC - A61K 31/4985: Pyrazines or piperazines ortho- or peri-condensed with heterocyclic ring systems - A61K 31/138: Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine (atenolol A61K31/165; pindolol A61K31/404; timolol A61K31/5377) - A61K 31/18: Sulfonamides (compounds containing a para-N-benzene-sulfonyl-N- group A61K31/63) - A61K 31/185: Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids (hydroxamic acids A61K31/16; peroxy acids A61K31/327) - A61K 31/48: Ergoline derivatives, e.g. lysergic acid, ergotamine - A61K 31/517: ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - 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) ## Abstract A method of treating an ocular disorder in a subject includes administering to the subject subtherapeutic amounts of two or more agents that inhibit and/or blocks the activation of Gs- or Gq-protein coupled receptors or Gs- or Gq-signaling cascade in ocular cells of the subject, and/or activates Gi-protein coupled receptors, which is induced or triggered by light induced all-trans-retinal generation. ## Claims ### Claim 1 A method of treating an ocular disorder associated with light induced retinal degeneration, aberrant all-trans-retinal clearance, or reactive oxygen species generation in the retina of a subject, comprising: administering to the subject a subtherapeutic amounts of two or more agents that inhibit and/or blocks the activation of Gs- or Gq-protein coupled receptors or Gs- or Gq-signaling cascade in ocular cells of the subject, and/or activates Gi-protein coupled receptors, which is induced or triggered by light induced all-trans-retinal generation. ### Claim 2 (depends on 1) The method of claim 1, the agents consisting of at least two of a Gs or Gq coupled serotonin receptor antagonists, Dopamine receptor D1 antagonists, Dopamine receptor D5 antagonists, β1 adrenergic receptor antagonists, β2 adrenergic receptor antagonists, Adenosine A2B receptor antagonists, corticotropin releasing hormone receptor 1 antagonists, metabotropic glutamate receptor 1 antagonists, and tachykinin receptor 1 antagonist, and prostaglandin E receptor 1 antagonists, dopamine receptor D2 agonists, dopamine receptor D3 agonists, dopamine receptor D4 agonists, and metabotropic glutamate receptor 4 agonists, an alpha-2 adrenergic receptor agonist, an adenylyl cyclase inhibitor, an M3 receptor antagonist, or a PLC inhibitor. ### Claim 3 (depends on 1) The method of claim 1, wherein the agents comprise at least two of a Gi-coupled dopamine D2 receptor agonist, a Gs-coupled β1 adrenergic receptor antagonist, or a Gq-coupled α1 adrenergic receptor blocker. ### Claim 4 (depends on 1) The method of claim 1, wherein the agents comprise at least two of bromocriptine, metoprolol, tamsulosin, or doxazosin. ### Claim 5 (depends on 1) The method of claim 1, wherein the agents comprise bromocriptine, metoprolol, and tamsulosin. ### Claim 6 (depends on 1) The method of claim 1, wherein the agents comprise bromocriptine, metoprolol, and doxazosin. ### Claim 7 (depends on 1) The method of claim 1, the agents being delivered to the subject by at least one of topical administration, systemic administration, intravitreal injection, and intraocular delivery. ### Claim 8 (depends on 1) The method of claim 1, the agents being provided in an ocular preparation for sustained delivery. ### Claim 9 (depends on 1) The method of claim 1, the ocular disorder comprising at least one of macular degeneration, geographic atrophy (GA), Stargardt disease, retinitis pigmentosa, and diabetic retinopathy. ### Claim 10 A method of treating geographic atrophy (GA), Stargardt disease, macular degeneration, retinitis pigementosa, or diabetic retinopathy in a subject, the method comprising: administering to the subject a subtherapeutic amounts of two or more agents that inhibit and/or blocks the activation of Gs- or Gq-protein coupled receptors or Gs- or Gq-signaling cascade in ocular cells of the subject, and/or activates Gi-protein coupled receptors, which is induced or triggered by light induced all-trans-retinal generation. ### Claim 11 (depends on 10) The method of claim 10, the agents consisting of at least two of a Gs or Gq coupled serotonin receptor antagonists, Dopamine receptor D1 antagonists, Dopamine receptor D5 antagonists, β1 adrenergic receptor antagonists, β2 adrenergic receptor antagonists, Adenosine A2B receptor antagonists, corticotropin releasing hormone receptor 1 antagonists, metabotropic glutamate receptor 1 antagonists, and tachykinin receptor 1 antagonist, and prostaglandin E receptor 1 antagonists, dopamine receptor D2 agonists, dopamine receptor D3 agonists, dopamine receptor D4 agonists, and metabotropic glutamate receptor 4 agonists, an alpha-2 adrenergic receptor agonist, an adenylyl cyclase inhibitor, an M3 receptor antagonist, or a PLC inhibitor. ### Claim 12 (depends on 10) The method of claim 10, wherein agents comprise at least two of a Gi-coupled dopamine D2 receptor agonist, a Gs-coupled β1 adrenergic receptor antagonist, or a Gq-coupled α1 adrenergic receptor blocker. ### Claim 13 (depends on 10) The method of claim 10, wherein the agents comprise at least two of bromocriptine, metoprolol, tamsulosin, or doxazosin. ### Claim 14 (depends on 10) The method of claim 10, wherein the agents comprise bromocriptine, metoprolol, and tamsulosin. ### Claim 15 (depends on 10) The method of claim 10, wherein the agents comprise bromocriptine, metoprolol, and doxazosin. ### Claim 16 (depends on 10) The method of claim 10, the agents being delivered to the subject by at least one of topical administration, systemic administration, intravitreal injection, and intraocular delivery. ### Claim 17 (depends on 10) The method of claim 10, the agents being provided in an ocular preparation for sustained delivery.