ASSESSMENT OF THE SELECTIVITY OF OPC‐2009, A NEW β2‐ADRENOCEPTOR STIMULANT, BY THE USE OF THE BLOOD‐PERFUSED TRACHEA in situ AND OF THE ISOLATED BLOOD‐PERFUSED PAPILLARY MUSCLE OF THE DOG

1 The potency and selectivity of 5‐(1‐hydroxy‐2‐isopropylamino)butyl‐8‐hydroxy carbostyril hydrochloride hemihydrate (OPC‐2009), a new β2‐adrenoceptor stimulant, was compared with those of isoprenaline, trimetoquinol and salbutamol by the use of blood‐perfused tracheal preparations in situand of blood‐perfused papillary muscle preparations of the dog. All drugs were injected intra‐arterially. 2 All the four drugs decreased tracheal intraluminal pressure (tracheal relaxation) and increased tracheal blood flow in a dose‐dependent manner. The four drugs produced a dose‐dependent increase in developed tension of papillary muscles. In both preparations the duration of action of isoprenaline and salbutamol was short, whereas that of OPC‐2009 and trimetoquinol was long. These effects were antagonized by propranolol. 3 Dose‐response curves to the four drugs for tracheal relaxation were almost parallel. OPC‐2009 was 2.4 times more potent, and trimetoquinol and salbutamol were 2.2 and 6.2 times less potent than isoprenaline in causing tracheal relaxation. 4 Dose‐response curves to the four drugs for tracheal vasodilatation were also parallel. OPC‐2009, trimetoquinol and salbutamol were 3.9, 6.7 and 23 times less potent than isoprenaline. 5 Slopes of the dose‐response curves to the four drugs for increased developed tension were not parallel; that of OPC‐2009 was the least steep, whereas that of isoprenaline was the steepest. Trimetoquinol, salbutamol and OPC‐2009 were about 18, 570 and 2400 times less potent than isoprenaline. 6 Selectivity calculated from relative potencies indicate that OPC‐2009 was about 6000 times, salbutamol about 92 times and trimetoquinol about 8.2 times more selective than isoprenaline for tracheal smooth muscle as compared to ventricular muscle. 7 The high potency and selectivity of OPC‐2009 for tracheal smooth muscle and its long duration of action suggest its potential usefulness for treatment of bronchial asthma. 8 The present results are also compatible with the concept that β1‐adrenoceptors in cardiac muscle and β2‐adrenoceptors in tracheal and vascular smooth muscle can be distinguished. Furthermore, the results revealed that the β‐adrenoceptors mediating tracheal relaxation and vasodilatation may also be different.