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Methylxanthines in Asthma

  • Stephen L. TilleyEmail author
Chapter
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 200)

Abstract

Methylxanthines represent a unique class of drugs for the treatment of asthma. The methylxanthine theophylline has demonstrated efficacy in attenuating the three cardinal features of asthma – reversible airflow obstruction, airway hyperresponsiveness, and airway inflammation. At doses achieving relatively high serum levels in which toxic side effects are sometimes observed, direct bronchodilatory effects of theophylline are recognized. At lower serum concentrations, theophylline is a weak bronchodilator but retains its capacity as an immunomodulator, anti-inflammatory, and bronchoprotective drug. Intense investigation into the molecular mechanisms of action of theophylline has identified several different points of action. Phosphodiesterase inhibition and adenosine receptor antagonism have both been implicated in promoting airway smooth muscle relaxation and bronchodilation. Similar mechanisms of action may explain the inhibitory effects of theophylline on immune cells. At lower concentrations that fail to inhibit phosphodiesterase, effects on histone deacetylase activity are believed to contribute to the immunomodulatory actions of theophylline. Since anti-inflammatory and immunomodulatory effects of methylxanthines are realized at lower serum concentrations than are required for bronchodilation, theophylline’s predominant role in asthma treatment is as a controller medication for chronic, persistent disease.

Keywords

Adenosine receptors Airway smooth muscle Asthma Mast cell Methylxanthines Phosphodiesterase Theophylline 

Abbreviations

ASM

Airway smooth muscle

cAMP

Cyclic AMP

cGMP

Cyclic GMP

HDAC

Histone deacetylase

ICS

Inhaled corticosteroids

PDE

Phosphodiesterase

PPARγ

Peroxisome-proliferator-activated receptor γ

RyR

Ryanodine receptor

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© Springer Berlin Heidelberg 2011

Authors and Affiliations

  1. 1.Department of Medicine, Division of Pulmonary and Critical Care Medicine, and Center for Environmental Medicine, Asthma, and Lung BiologyUniversity of North CarolinaChapel HillUSA

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