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Progress in Drug Research pp 193–229Cite as

Birkhäuser

Phosphodiesterase 4 (PDE4) inhibitors in asthma and chronic obstructive pulmonary disease (COPD)

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Part of the book series: Progress in Drug Research ((PDR,volume 53))

Summary

Phosphodiesterases (PDE) are a family of enzymes responsible for the metabolism of the intracellular second messengers cyclic AMP and cyclic GMP. PDE4 is a cyclic AMP specific PDE that is the major if not sole cyclic AMP metabolizing enzymes found in inflammatory and immune cells, and contributes significantly to cyclic AMP metabolism in smooth muscles. Based on its cellular and tissue distribution and the demonstration that selective inhibitors of this isozyme reduce bronchoconstriction in animals and suppress the activation of inflammatory cells, PDE4 has become an important molecular target for the development of novel therapies for asthma and COPD. This chapter will review the evidence demonstrating the ability of PDE4 inhibitors to modify airway obstruction, airway inflammation and airway remodelling and hyperreactivity, will present some preliminary findings obtained with theses compounds in clinical trials and and will discuss experimental approaches designed to identify novel compounds that maintain the beneficial activity of the initial selective PDE4 inhibitors but with a reduced tendency to elicit the gastrointestinal side effects observed with this class of compounds.

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Abbreviations

BAL:

bronchoalveolar lavage

CNS:

central nervous system

COPD:

chronic obstructive pulmonary disease

cyclic AMP:

3’5’ cyclic adenosine monophosphate

cyclic GMP:

3’5’ cyclic guanosine monophosphate

FEV1 :

forced expiratory volume in one second

fMLP:

formyl methionine leucine phenylalanine

GM-CSF:

granulocyte mocrophage colony stimulating factor

5-HT:

5-hydroxytryptamine

HPDE4:

high affinity phosphodiesterase4

IL:

interleukin

LPS:

lipopolysaccharide

LPDE4:

low affinity phosphodiesterase 4

LTB4 :

leukotriene B4

LTD4 :

leukotriene D4

NANC:

non-cholinergic, non adrenergic

NO:

nitric oxide

PAF:

platelet activating factor

PGE2 :

prostaglanding E2

PDE:

phosphodiesterase

RNA:

ribonucleic acid

TNF:

tumor necrosis factor

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  1. Pulmonary Pharmacology, SmithKline Beecham Pharmaceuticals, 709 Swedeland Road, King of Prussia, PA, 19406-0939, USA

    Mary S. Barnette

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    Ernst Jucker

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Barnette, M.S. (1999). Phosphodiesterase 4 (PDE4) inhibitors in asthma and chronic obstructive pulmonary disease (COPD). In: Jucker, E. (eds) Progress in Drug Research. Progress in Drug Research, vol 53. Birkhäuser, Basel. https://doi.org/10.1007/978-3-0348-8735-9_5

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