Inhibition by viozan of extravasation induced in rat trachea by capsaicin is mediated exclusively by beta(2)-adrenoceptors

The mechanism by which 2(3H)-benzothiazolone, 4-hydroxy-7-[2-[[2-[[3-(2-phe nylethoxy)propyl]sulphonyl]ethyl]amino]ethyl]-monohydrochloride (ARC68397AA ; viozan), a dual dopamine D-2/beta (2)-adrenoceptor agonist which has show n promise in the treatment of chronic obstructive pulmonary disease (COPD), inhibits the extravasation of plasma protein induced by capsaicin in the t racheas of Brown Norway rats has been re-evaluated. Viozan (10-30 mug/kg given intratracheally; i.t.) inhibited dose-dependentl y the extravasation of plasma protein tagged with Evans Blue into rat trach ea induced by capsaicin (10 mug/kg i.t.). Similar effects were seen with th e selective beta (2)-adrenoceptor agonist, salbutamol (3-10 mug/kg i.t.), b ut the selective dopamine D-2 receptor agonist, quinagolide (10-30 mug/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 sulp iride (3 mg/kg i.p.). Thus, in c,ontrast to claims in the literature, a functional response to do pamine D-2 receptor activation in a preclinical model of oedema arising fro m sensory nerve fibre activation in the rat lung could not be demonstrated. Moreover, no qualitative difference could be demonstrated between the resp onse to a dual D-2/beta (2)-adrenoceptor agonist and a selective beta (2)-a drenoceptor agonist. The observations call into question whether a dual D-2 /beta (2)-adrenoceptor agonist such as viozan would bring added benefit ove r established selective beta (2)-adrenoceptor agonists in the therapy of CO PD.