Antitussive compositions and methods

Abstract

Disclosed herein are compositions which include nicotinic receptor agonists, specifically of the α7 nAChR subtype, and methods for suppressing cough.

What is claimed is: 
     
         1 .- 20 . (canceled) 
     
     
         21 . A method of suppressing cough in a subject comprising administering to the subject in need thereof a therapeutically effective amount of an α7 nicotinic receptor agonist. 
     
     
         22 . The method of  claim 21 , wherein the α7 nicotinic receptor agonist is chosen from Octahydro-2-methyl-5-(6-phenyl-3-pyridazinyl)-pyrrolo[3,4-c]pyrrole (A 582941), N-[(3R)-1-azabicyclo[2.2.2]oct-3-yl]-7-[2-(methoxy)phenyl]-1-benzofuran-2-carboxamide (ABBF), ABT-418 hydrochloride (CAS 147388-83-8), acetylcholine, anabaseine, (2S)-2′H-spiro[4-azabicyclo[2.2.2]octane-2,5′-[1,3]oxazolidin]-2′-one (AR-R17779), 3′H-4-Azaspiro[bicyclo[2.2.2]octane-2,2′-furo[2,3-b]pyridine] (AZD0328), choline, cytosine, 3-(2,4-dimethoxybenzylidene)anabaseine (DMXB-A; DMBX-anabaseine, GTS-21 dihydrochloride), epibatidine, imidacloprid, lobeline, (S)-(1-aza-bicyclo[2.2.2]oct-3-yl)carbamic acid (S)-1-(2-fluorophenyl)ethyl ester HCl salt (JN403), R3487/MEM 3454, nicotine, N-(3R)-1-Azabicyclo[2.2.2]oct-3-yl-furo[2,3-c]pyridine-5-carboxamide hydrochloride (PHA-543613), N-(3R)-1-Azabicyclo[2.2.2]oct-3-yl-4-chlorobenzamide (PNU-282987), pyridol, N-[4-(3-pyridinyl)phenyl]-4-morpholinepentanamide (SEN12333, WAY 317538), 1,4-Diazabicyclo[3.2.2]nonane-4-carboxylic acid, 4-bromophenyl ester (SSR180711), (R,R; R,S; S,R; and S,S)—N-(2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)benzofuran-2-carboxamide (TC-5619), (2S,3R)—N-2-((3-pyridinyl)methyl)-1-azabicyclo[2.2.2]oct-3-yl)-3,5-difluorobenzamide (TC-6987),varenicline, 4-(4-Bromophenyl)-3a,4,5,9b-tetrahydro-3H-cyclopenta[c]quinoline-8-sulfonamide (4BP-TQS), 2-(Hexahydro-5-methylpyrrolo[3,4-c]pyrrol-2(1H)-yl)-9H-xanthen-9-one (A 844606), (2S)-2′H-spiro[4-azabicyclo[2.2.2]octane-2,5′-[1,3]oxazolidin]-2′-one (AR-R 17779), 3-Bromocytisine, 4-[(5,6-Dihydro[2,3′-bipyridin]-3 (4H)-ylidene)methyl]-N,N-dimethylbenzenamine dihydrochloride (DMAB-anabaseine dihydrochloride), N-(3R)-1-Azabicyclo[2.2.2]oct-3-yl-furo[2,3-c]pyridine-5-carboxamide hydrochloride (PHA 543613 hydrochloride), N-(3R)-1-Azabicyclo[2.2.2]oct-3-yl-2,3-dihydro-1,4-benzodioxin-6-carboxamide fumarate (PHA 568487), 2-[2-(4-Bromophenyl)-2-oxoethyl]-1-methylpyridinium iodide (S 24795), N-[4-(3-pyridinyl)phenyl]-4-morpholinepentanamide (SEN 12333, WAY 317538), h2-(3-Pyridinyl)-1-azabicyclo[3.2.2]nonane dihydrochloride (TC-1698 dihydrochloride). 
     
     
         23 . The method of  claim 21  further comprising administering to said subject one or more additional pharmaceutically active ingredients chosen from antitussives other than nicotine or a derivative thereof, antipyretics, expectorants, mucolytics, nasal decongestants, antihistamines, opioid analgesics, or non-opiate analgesics. 
     
     
         24 . The method of  claim 23  wherein the antitussive is chosen from ambroxol, apomorphine hydrochloride, beechwood creosote, benzonatate, camphor ethanedisulfonate, caramiphen edisylate, carbetapentane citrate, chlophendianol hydrochloride, codeine, codeine phosphate, codeine sulfate, dextromethorphan, dextromethorphan hydrobromide, diphenhydramine, diphenhydramine hydrochloride, fentanyl, fentanyl citrate, hydrocodone, hydromorphone hydrochloride, levorphanol tartrate, menthol, methadone hydrochloride, morphine, morphine sulfate, noscapine, noscapine hydrochloride, oxycodone hydrochloride, oxymorphone hydrochloride or zinc gluconate. 
     
     
         25 . The method of  claim 23  wherein the expectorant is chosen from acetylcysteine, ammonium carbonate, ammonium chloride, antimony potassium tartrate, glycerin, guaifenesin, potassium iodide, sodium citrate, terpin hydrate, or tolu balsam. 
     
     
         26 . The method of  claim 23  wherein the mucolytic is chosen from acetylcysteine, ambroxol, bromhexine, carbocisteine, domiodol, dornase alfa, eprazinone, erdosteine, letosteine, mesna, neltenexine, sobrerol, stepronin, or tiopronin. 
     
     
         27 . The method of  claim 23  wherein the nasal decongestant is chosen from ephedrine, ephedrine hydrochloride, ephedrine sulfate, epinephrine bitartrate, hydroxyamphetamine hydrobromide, mephentermine sulfate, methoxamine hydrochloride, naphazoline hydrochloride, oxymetalozine hydrochloride, phenylpropanolamine hydrochloride, propylhexedrine, psuedoephedrine hydrochloride, tetrahydrozoline hydrochloride, or xylometazoline hydrochloride. 
     
     
         28 . The method of  claim 23  wherein the antihistamine is chosen from antazoline, azatadine, brompheniramine, brompheniramine mepyramine, carbinoxamine, chlorcyclizine, chlorpheniramine, chlorpheniramine, clemastine, cyclizine, cyproheptadine, dexchlorpheniramine, dimenhydrinate, dimetindene, diphenhydramine, diphenhydramine, doxylamine, doxylamine, hydroxyzine, ketotifen, meclizine, pheniramine, promethazine, trimeprazine, or triprolidine. 
     
     
         29 . The method of  claim 23  wherein the opioid analgesic is chosen from codeine, diphenoxylate, fentanyl, hydrocodone, hydromorphone, levorphanol, meperidine, methadone, morphine, oxycodone, oxymorphone, or propoxyphene. 
     
     
         30 . The method of  claim 23  wherein the non-opioid analgesic is chosen from memantine, acetaminophen, aspirin, ibuprofen, or naproxen. 
     
     
         31 . The method of  claim 21  wherein the nicotinic receptor agonist is administered in the form of a capsule, elixir, fast-melt strip, gum, lozenge, liquid, lotion, nasal-inhaled spray, oral-inhaled spray, orally disintegrating tablet, syrup, tablet, or transdermal patch. 
     
     
         32 . The method of  claim 21  wherein the subject is a human. 
     
     
         33 . The method of  claim 21  wherein the nicotinic receptor agonist is administered once a day. 
     
     
         34 . The method of  claim 21  wherein the nicotinic receptor agonist is administered twice a day. 
     
     
         35 . The method of  claim 21  wherein the nicotinic receptor agonist is administered at least three times a day. 
     
     
         36 . The method of  claim 21  wherein the cough is a symptom of one or more conditions chosen from sneezing, rhinorrhea, nasal obstruction, nasal congestion, nasal pruritus, rhinorrhea, allergies, allergic vasomotor rhinitis (hay fever), seasonal allergic vasomotor rhinitis, perennial allergic vasomotor rhinitis, a respiratory disease, a cold, acute bronchitis, chronic bronchitis, asthmatic bronchitis, bronchiectasis, pneumonia, lung tuberculosis, silicosis, silicotuberculosis, pulmonary cancer, upper respiratory inflammation, pharyngitis, laryngitis, nasal catarrh, asthma, bronchial asthma, infantile asthma, pulmonary emphysema, pneumoconiosis, pulmonary fibrosis, pulmonary silicosis, pulmonary suppuration, pleuritis, tonsillitis, cough hives, post-viral cough, gastreoesophageal reflux disease, post-nasal drip, nasal congestion, sinusitis, whooping cough or the cough results from a procedure chosen from a bronchography or a bronchoscopy. 
     
     
         37 . The method of  claim 21  wherein the cough is acute. 
     
     
         38 . The method of  claim 21  wherein the cough is subacute. 
     
     
         39 . The method of  claim 21  wherein the cough is chronic. 
     
     
         40 . The method of  claim 21  wherein the nicotinic receptor agonist is administered orally or by intramuscular injection, subcutaneous injection, intraperitoneal injection, intrathecal, sublingual. 
     
     
         41 . A method of suppressing or reducing cough by orally consuming a cough suppressing or reducing amount of a nicotinic receptor agonist.