# US 2010/0168030 A1 · Methods and compositions for treatment of organophosphate-caused pathology > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2010/0168030 A1 - Document ID: US20100168030A1 - Status: Published application - Kind: A1 - Application number: 11/288,269 - Filed: 2005-11-29 - Published: 2010-07-01 - Earliest claimed: 2005-11-29 - Inventors: Csaba K. Zoltani; Gennady E. Platoff; Steven I. Baskin - Web page: https://patentgrep.com/patent/US20100168030A1 ## CPC - A61K 31/136: having the amino group directly attached to the aromatic ring, e.g. benzeneamine - A61K 31/00: Medicinal preparations containing organic active ingredients - A61K 31/138: Aryloxyalkylamines, e.g. propranolol, tamoxifen, phenoxybenzamine (atenolol A61K31/165; pindolol A61K31/404; timolol A61K31/5377) - 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 31/44: Non condensed pyridines; Hydrogenated derivatives thereof - A61K 45/06: Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca - A61P 9/06: Antiarrhythmics - 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 A method of treating an organophosphate toxin-caused cardiac abnormality is described which includes administering a pharmaceutical composition including a therapeutically effective amount of a chloride current modulator to an individual subject having a cardiac abnormality caused by intoxication with an organophosphate toxin. The chloride current modulator is effective to modulate a chloride conductance and thereby reduce a symptom or sign of an organophosphate toxin-caused cardiac abnormality, thus treating the toxin-caused cardiac abnormality. Optionally, included is administering a therapeutic agent to inhibit an organophosphate toxin-caused distortion of the action potential of myocytes, support restoration of usual intracellular ionic concentrations, and support an increase in cardiac contractility. A composition according to the invention is described which includes a chloride current modulator; and a therapeutic agent to inhibit an organophosphate toxin-induced distortion of the action potential of myocytes, support restoration of usual intracellular ionic concentrations, and support an increase in cardiac contractility. ## Claims ### Claim 1 A method of treating an organophosphate toxin-caused cardiac abnormality in an individual subject, comprising: administering a pharmaceutical composition comprising a therapeutically effective amount of a chloride current modulator to an individual subject having a cardiac abnormality caused by intoxication with an organophosphate toxin, the chloride current modulator effective to modulate a chloride conductance, thereby reducing a symptom or sign of a toxin-caused cardiac abnormality and treating the toxin-induced cardiac abnormality. ### Claim 2 (depends on 1) The method of claim 1 wherein the chloride current modulator is a modulator of IC1, swell. ### Claim 3 (depends on 1) The method of claim 1 wherein the chloride current modulator is selected from the group consisting of: a disulfonic stilbene, an arylaminobenzoate, a fenamate, an anthracene carboxylate, an indanylalkanoic acid, clofibric acid, a clofibric acid derivative, a sulfonylurea, a calixarene, suramin, and tamoxifen. ### Claim 4 (depends on 2) The method of claim 2 wherein the modulator of IC1, swell is selected from the group consisting of: 4,4′-diisothiocyanostilbene-2,2′-disulfonic acid (DIDS); 4,4′-dinitrostilbene-2,2′-disulfonic acid (DNDS); 4-acetamindo-4′-isothiocyanostilbene-2,2′-disulfonic acid (SITS); tamoxifen; 5-nitro-2-(3-phenylpropylamino) benzoic acid (NPPB); niflumic acid (NFA); flufenamic acid; anthracene-9-carboxylate (9AC); diphenylaminecarboxylate (DPC); 2-(p-chlorophenoxy)propionic acid (CPP); and indanyloxyacetic acid (IAA-94). ### Claim 5 (depends on 1) The method of claim 1 further comprising administering a therapeutic agent to inhibit organophosphate-induced distortion of the action potential of myocytes, support restoration of usual intracellular ionic concentrations, and support an increase in cardiac contractility. ### Claim 6 (depends on 5) The method of claim 5 wherein the therapeutic agent is a second current modulator. ### Claim 7 (depends on 5) The method of claim 5 wherein the therapeutic agent is an antiarrhythmic drug. ### Claim 8 (depends on 5) The method of claim 5 wherein the therapeutic agent is a modulator of a mitochondrial membrane moiety selected from the group consisting of: an ion channel, an ion pump, an ion exchanger, and a combination thereof. ### Claim 9 (depends on 5) The method of claim 5 wherein the therapeutic agent is an inhibitor of protein kinase C. ### Claim 10 (depends on 5) The method of claim 5 wherein the therapeutic agent is an anticonvulsant. ### Claim 11 (depends on 5) The method of claim 5 wherein the therapeutic agent is an organophosphate clearing agent. ### Claim 12 (depends on 11) The method of claim 11 wherein the organophosphate clearing agent is selected from the group consisting of: obidoxime, asoxime, pralidoxime, a salt thereof; and a combination thereof. ### Claim 13 (depends on 1) The method of claim 1 wherein the cardiac abnormality is ventricular fibrillation. ### Claim 14 (depends on 1) The method of claim 1 wherein the cardiac abnormality is cardiogenic shock. ### Claim 15 (depends on 6) The method of claim 6 wherein the second current modulator is an inhibitor of a muscarinic potassium channel. ### Claim 16 (depends on 15) The method of claim 15 wherein the inhibitor of a muscarinic potassium channel is selected from the group consisting of: tertiapin, tertiapin-Q, and a combination thereof. ### Claim 17 (depends on 5) The method of claim 5 wherein the therapeutic agent is an acetylcholine receptor antagonist. ### Claim 18 A pharmaceutically effective amount of a composition consisting of: a chloride current modulator of IC1 swell; and a combination therapeutic agent limited to the class of agents that in a single dose inhibit organophosphate-caused distortion of the action potential of myocytes, support restoration of usual intracellular ionic concentrations, and support an increase in cardiac contractility. ### Claim 19 (canceled) ### Claim 20 (depends on 18) The composition of claim 18 wherein the therapeutic agent is selected from the group consisting of: a second current modulator, an antiarrhythmic drug, an acetylcholine receptor antagonist, an anticonvulsant, an organophosphate clearing agent, an inhibitor of protein kinase C, a modulator of a mitochondrial membrane moiety, and a combination thereof.