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  • Title: Dual-pharmacology muscarinic antagonist and β₂ agonist molecules for the treatment of chronic obstructive pulmonary disease.
    Author: Hughes AD, Jones LH.
    Journal: Future Med Chem; 2011 Oct; 3(13):1585-605. PubMed ID: 21942250.
    Abstract:
    Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death in the world today. Bronchodilators, particularly muscarinic antagonists and β(2) agonists, are recommended for patients with moderate to severe COPD. Dual-pharmacology muscarinic antagonist- β(2) agonist (MABA) molecules present an exciting new approach to the treatment of COPD by combining muscarinic antagonism and β(2) agonism in a single entity. They have the potential to demonstrate additive or synergistic bronchodilation over either pharmacology alone. Due to this enticing prospect, several companies have now reported MABA discovery efforts through a conjugated/linked strategy with one candidate (GSK-961081) demonstrating clinical proof of concept. Several MABA crystal forms have been identified, satisfying the requirements for inhaled dosing devices. There are significant challenges in designing MABAs, but the potential to achieve enhanced bronchoprotection in patients and facilitate 'triple therapy' makes this an extremely important and exciting area of pharmaceutical research.
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