Studies using KWD 2058, a derivative of terbutaline in isolated atrial and tracheal preparations from the guinea-pig.
KWD 2058 is a derivative of terbutaline in which the ring hydroxy groups are esterified with isobutyric acid. In guinea-pig atrial and tracheal preparations KWD 2058 produced slowly developing beta-receptor mediated actions which were absent in preparations pretreated with physostigmine. Incubation of KWD 2058 with guinea-pig plasma resulted in the production of a compound which was indistinguishable from terbutaline on both a qualitative and quantitative basis. KWD 2058 produced negative inotropic and chronotropic actions and increased the effective refractory period of guinea-pig atria. In addition, KWD 2058 produced a non-competitive antagonism of chronotropic responses to (--)-isoprenaline in atria. It is concluded that KWD 2058 has no affinity for beta-adrenoreceptors and that any beta-agonistic activity displayed is due to its hydrolysis product, terbutaline.
D000818:Animals; D002087:Butyrates / Q000494:pharmacology; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects*; D009200:Myocardial Contraction / Q000187:drug effects; D010830:Physostigmine / Q000494:pharmacology; D011941:Receptors, Adrenergic / Q000187:drug effects; D012032:Refractory Period, Electrophysiological / Q000187:drug effects; D013268:Stimulation, Chemical; D013726:Terbutaline / Q000031:analogs & derivatives* / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects
D002087:Butyrates; D011941:Receptors, Adrenergic; C011287:ibuterol; D010830:Physostigmine; D007545:Isoproterenol; D013726:Terbutaline