The beta-adrenoceptor stimulant properties of OPC-2009 on guinea-pig isolated tracheal, right atrial and left atrial preparations.
1. The beta-adrenoceptor stimulant properties of 5-(1-hydroxy-2-isopropylaminobutyl)-8-hydroxy-carbostyril hydrochloride hemihydrate (OPC-2009) were compared with those of isoprenaline and salbutamol on guinea-pig isolated tissues. 2. In producing tracheal relaxation, OPC-2009 was approximately 7 times more potent and salbutamol 5 times less potent than isoprenaline. Both compounds were less potent than isoprenaline in increasing either the rate of beating of isolated right atria or the contractile force of left atria, OPC-2009 being 4 and 127 times and salbutamol being 100 and 700 times less potent on the respective preparations. 3. Selectivity calculated from EC50 ratio indicates that OPC-2009 was approximately 26 times and salbutamol approximately 21 times more selective than isoprenaline for tracheal smooth muscle as compared to right atrial muscle, whereas OPC-2009 was approximately 850 times and salbutamol 140 times more selective than isoprenaline for tracheal smooth muscle as compared to left atria. 4. The responses to OPC-2009 on trachea and right atria were not altered by treatment of animals with reserpine 24 h previously. Propranolol was a competitive antagonist of OPC-2009 on these tissues. 5. OPC-2009 at high concentrations competitively antagonized the positive chronotropic and inotropic responses to isoprenaline, indicating that OPC-2009 like salbutamol, may be classified as a partial agonist. 6. The results indicate that the action of OPC-2009 is more selective for tracheal smooth muscle than cardiac muscle and are interpreted in the light of subdivisions of beta-adrenoceptors.
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D002217:Carbachol / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006912:Hydroxyquinolines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects; D011433:Propranolol / Q000494:pharmacology; D013268:Stimulation, Chemical; D014132:Trachea / Q000187:drug effects*
D000318:Adrenergic beta-Agonists; D006912:Hydroxyquinolines; D002217:Carbachol; D011433:Propranolol; D007545:Isoproterenol; D000420:Albuterol