title: Investigational beta-2 adrenergic agonists for the treatment of chronic obstructive pulmonary disease.
abstract: Long-acting bronchodilators are pivotal in the therapeutic management of COPD patients with moderate-to-severe airflow obstruction. New ultra-long-acting β2-agnoists (ultra-LABAs) have been developed, some of which have been licensed for use as monotherapy and/or in combination with other bronchodilators or inhaled corticosteroids, for use in COPD patients with persistent symptoms and worsening airflow limitation. These new agents are faster in onset and have a prolonged duration of action, with a similar safety profile to the traditional twice-daily bronchodilators which may have an impact on patient concordance. Areas covered: A number of these ultra-LABAs are still under development and bi-functional hybrid molecules containing regions functioning as β2-agonists, and as muscarinic agonists (MABAs) has been developed. This review summarizes these (excluding the licensed ultra-LABAs) with attention on phase II studies data available to-date on their pharmacological profiles, clinical efficacy and safety, and future perspectives. Expert opinion: Despite all the new agents' available, the challenges that persist include any differences in efficacy and safety between the various possible LAMA/LABA combinations, relative advantages of MABAs over fixed-dose LAMA/LABAs, and the impact of these new molecules in terms of long term safety, especially in certain populations in co-morbidities frequently associated with COPD.
authors.affiliation: a Department of Internal Medicine , University of Brescia and ASST Spedali Civili , Brescia , Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Malerba
authors.affiliation: b Department of Emergency , ASST Spedali Civili , Brescia , Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Radaeli
authors.affiliation: c Department of Pharmacology, Faculty of Medicine , University Hospital Agostino Gemelli Foundation Catholic University of the Sacred Heart, Pharmacology , Rome , Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Montuschi
authors.affiliation: d Department of Respiratory Medicine , Queen Alexandra Hospital, Cosham , Portsmouth , UK.
authors.forename: Kesavan S
authors.initials: KS
authors.lastname: Babu
authors.affiliation: e Department of Respiratory Medicine , Royal Brompton & Harefield NHS Trust, Harefield Hospital , Harefield , UK.
authors.forename: Jaymin B
authors.initials: JB
authors.lastname: Morjaria
mesh_terms: D058666:Adrenergic beta-2 Receptor Agonists / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D001993:Bronchodilator Agents / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D003692:Delayed-Action Preparations; D015195:Drug Design; D015507:Drugs, Investigational / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D018727:Muscarinic Antagonists / Q000009:adverse effects / Q000494:pharmacology / Q000627:therapeutic use; D029424:Pulmonary Disease, Chronic Obstructive / Q000188:drug therapy* / Q000503:physiopathology
chemical_list: D058666:Adrenergic beta-2 Receptor Agonists; D001993:Bronchodilator Agents; D003692:Delayed-Action Preparations; D015507:Drugs, Investigational; D018727:Muscarinic Antagonists
keywords: Bronchodilators; COPD; COPD treatment; long acting beta agonists