The β2-adrenoceptor agonist bronchodilators terbutaline and orciprenaline are also weak α1-adrenoceptor antagonists

• Published in: European journal of pharmacology 2020-09, Vol.882, p.173304-173304, Article 173304
• Main Authors: Khammy, Makhala M., Truong, Cindy Kha Han, Wright, Christine E., Angus, James A.
• Format: Article
• Language: English
• Subjects: Clark plot; Competitive α1-adrenoceptor antagonism; Orciprenaline; Rat small mesenteric arteries; Terbutaline
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2020.173304

Recently, the β2-adrenoceptor agonist terbutaline was shown to have α1-adrenolytic activity in mouse isolated pulmonary arteries in vitro and to lower pulmonary artery pressure in anaesthetised mice. The aim of our study was to determine the α1-adrenoceptor antagonist activity of terbutaline and its structurally close resorcinol, orciprenaline, in rat isolated small mesenteric arteries set up for myography. Their α1-adrenoceptor antagonist potency was then compared with their potency as β2-adrenoceptor agonists. Concentration-response curves to methoxamine were competitively antagonised by terbutaline (30–300 μM) or orciprenaline (30–300 μM) with a pKB of 4.70 ± 0.09 or 4.79 ± 0.17, respectively. Both terbutaline and orciprenaline fulfilled the criteria for simple, silent competitive antagonism. Terbutaline (30–300 μM) had no effect on endothelin-1 concentration-contraction curves. Our findings suggest that after oral dosing of terbutaline, the maximum plasma levels would NOT reach levels to show α1-adrenoceptor antagonist activity. In conclusion, our work has provided additional quantitative evidence that terbutaline and orciprenaline are weak competitive α1-adrenoceptor antagonists, but this additional property is probably not therapeutically important in the clinical treatment of asthma or pulmonary artery hypertension with these more potent β2-adrenoceptor agonists.