Method of treating airway diseases with beta-adrenergic inverse agonists

Abstract

The use of β-adrenergic inverse agonists provides a new and highly efficient way of treating a number of pulmonary airway diseases, including asthma, emphysema, and chronic obstructive pulmonary diseases. In general, such a method comprises administering a therapeutically effective amount of a β-adrenergic inverse agonist to the subject to treat the pulmonary airway disease. Particularly preferred inverse agonists include nadolol and carvedilol. In addition, methods are described for long-term administration of such inverse agonists and for determining the suitability of patients for long-term inverse agonist therapy.

1 . A pharmaceutical composition comprising:
 (a) a dosage of nadolol selected from the group consisting of 1 mg, 3 mg, 5 mg, 10 mg, 15 mg, 20 mg, 25 mg, 30 mg, 40 mg, 50 mg, 60 mg, 70 mg, 80 mg, 90 mg, 100 mg, 110 mg, 120 mg, 130 mg, 140 mg, 150 mg, and 160 mg; and   (b) a pharmaceutically acceptable carrier;   
       the pharmaceutical composition being formulated for long-term treatment of a respiratory disease or condition treatable by chronic administration of a beta-adrenergic inverse agonist. 
     
     
         2 . The pharmaceutical composition of  claim 1  wherein the disease or condition treatable by chronic administration of a beta-adrenergic inverse agonist is selected from the group consisting of asthma and chronic obstructive pulmonary disease. 
     
     
         3 . The pharmaceutical composition of  claim 2  wherein the disease or condition treatable by chronic administration of a beta-adrenergic inverse agonist is asthma. 
     
     
         4 . The pharmaceutical composition of  claim 2  wherein the disease or condition treatable by chronic administration of a beta-adrenergic inverse agonist is chronic obstructive pulmonary disease. 
     
     
         5 . The pharmaceutical composition of  claim 1  wherein the composition is formulated for sustained release. 
     
     
         6 . A method of testing a patient suffering from a respiratory disease or condition treatable by administration of a beta-adrenergic inverse agonist to determine the suitability of the patient for long-term treatment with a beta-adrenergic inverse agonist comprising the steps of:
 (a) measuring at least one diagnostic parameter potentially affected by the administration of the beta-adrenergic inverse agonist in the patient to be tested;   (b) administering a minimum daily dose of the beta-adrenergic inverse agonist to the patient for a predetermined period of time; and   (c) measuring the at least one diagnostic parameter subsequent to the administration of the beta-adrenergic inverse agonist in order to determine whether the patient is suitable for long-term treatment with the beta-adrenergic inverse agonist.   
     
     
         7 . The method of  claim 6  wherein the disease or condition treatable by the beta-adrenergic inverse agonist is selected from the group consisting of asthma and chronic obstructive pulmonary disease. 
     
     
         8 . The method of  claim 7  wherein the disease or condition treatable by the beta-adrenergic inverse agonist is asthma. 
     
     
         9 . The method of  claim 7  wherein the disease or condition treatable by the beta-adrenergic inverse agonist is asthma. 
     
     
         10 . The method of  claim 6  wherein the beta-adrenergic inverse agonist is nadolol. 
     
     
         11 . A method for treating a disease or condition treatable by chronic administration of a beta-adrenergic inverse agonist, the disease or condition being a respiratory disease or condition, wherein the respiratory disease is chronic obstructive pulmonary disease (COPD). 
     
     
         12 . The method of  claim 11 , wherein the beta-adrenergic inverse agonist is ICI 118,551. 
     
     
         13 . The method of  claim 11 , wherein the beta-adrenergic inverse agonist is nadolol.