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- Title
Inhibition by viozan of extravasation induced in rat trachea by capsaicin is mediated exclusively by β<sub>2</sub>-adrenoceptors.
- Authors
Fozard, John R.; Baur, François; Wolber, Cedric; Collingwood, Stephen P.
- Abstract
The mechanism by which 2(3H)-benzothiazolone, 4-hydroxy-7-[2-[[2-[[3-(2-phenylethoxy)propyl]sulphonyl]ethyl]amino]ethyl]-monohydrochloride (AR-C68397AA; viozan), a dual dopamine D2/β2-adrenoceptor agonist which has shown promise in the treatment of chronic obstructive pulmonary disease (COPD), inhibits the extravasation of plasma protein induced by capsaicin in the tracheas of Brown Norway rats has been re-evaluated. Viozan (10–30 µg/kg given intratracheally; i.t.) inhibited dose-dependently the extravasation of plasma protein tagged with Evans Blue into rat trachea induced by capsaicin (10 µg/kg i.t.). Similar effects were seen with the selective β2-adrenoceptor agonist, salbutamol (3–10 µg/kg i.t.), but the selective dopamine D2 receptor agonist, quinagolide (10–30 µg/kg i.t.), was inactive. The effects of viozan and salbutamol were abolished by propranolol (3 mg/kg) given intraperitoneally (i.p.) but unaffected by sulpiride (3 mg/kg i.p.). Thus, in contrast to claims in the literature, a functional response to dopamine D2 receptor activation in a preclinical model of oedema arising from sensory nerve fibre activation in the rat lung could not be demonstrated. Moreover, no qualitative difference could be demonstrated between the response to a dual D2/β2-adrenoceptor agonist and a selective β2-adrenoceptor agonist. The observations call into question whether a dual D2/β2-adrenoceptor agonist such as viozan would bring added benefit over established selective β2-adrenoceptor agonists in the therapy of COPD.
- Subjects
RESPIRATORY organs; OBSTRUCTIVE lung diseases; NEUROTRANSMITTERS; CATECHOLAMINES; ADRENERGIC receptors; BLOOD proteins; LUNG diseases
- Publication
Naunyn-Schmiedeberg's Archives of Pharmacology, 2001, Vol 364, Issue 6, p570
- ISSN
0028-1298
- Publication type
Article
- DOI
10.1007/s00210-001-0488-8