New Bronchodilator Drugs
β 2-Adrenoceptor agonists are the gold standard for the symptomatic treatment of asthma, resulting in quick and effective bronchodilator relief, although they are not completely free from side-effects. A range of different pharmacological approaches is be
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Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..
154
2 2.1 2.2 2.2.1 2.2.2 2.3
Vasoactive Intestinal Peptide. . . . . . . . . . . . . . . . . . . . . . . . . . .. Localization..................................... VIP and Airway Smooth Musc1e . . . . . . . . . . . . . . . . . . . . . . . . .. Functional Response. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. Receptor Heterogeneity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. VIP Analogues . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..
154 154 155 155 156 157
3 3.1 3.2 3.3 3.4
Nitric Oxide . . . . . . . . . . . . . Nitric Oxide Synthesis. . . . . . . . NO and Airway Smooth Musc1e . . Clinical Studies. . . . . . . . . . . . Pro-intlamrnatory Properties ofNO
.. .. .. .. ..
158 158 158 159 161
4
Atrial Natriuretic Peptide. . . . . . . . . . . . . . . . . . . . . . . . . . . . ..
162
5 5.1 5.2
Phosphodiesterase 3 Inhibitors . . . . . . . . . . . . . . . . . . . . . . . . .. In Vitro Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .. In Vivo Studies. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..
164 164 165
6 6.1 6.2 6.3 6.4
Potassium Channel Openers . . . . . . Voltage-Dependent Channels . . . . . . Calcium-Activated Potassium Channels KATP Channels . . . . . . . . . . . . . . Inward Rectifiers. . . . . . . . . . . . .
.. .. .. .. ..
165 166 166 167 169
7
Conclusion......................................
169
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . ..
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Abstract .82-Adrenoceptor agonists are the gold standard for the symptomatic treatment of asthma, resulting in quick and effective bronchodilator relief, although they are not completely free from side-effects. A range of different pharmacological approaches is being actively pursued in order to achieve relaxation of airway smooth muscle comparable to that seen with .82-adrenoceptor agonists and by mechanisms distinct from activation of the .8-adrenoceptor without atC. P. Page et al. (eds.), Pharmacology and Therapeutics of Asthma and COPD © Springer-Verlag Berlin Heidelberg 2004
154
D. Spina
tendant side-effects. These various approaches include signalling via vasoactive intestinal polypeptide (VIP) receptors, activation of soluble and particulate guanylyl cyclase, inhibition of phosphodiesterase (PDE)3 and opening of potassium channels. The pharmacology, clinical experience and merit of each of these novel approaches are discussed. Keywords VIP· Nitri
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