Pharmacologic potency and selectivity of a new bronchodilator agent, 2,3-dihydro-7-methyl-9-phenyl-1H-pyrazolo [1,2-a] indazolium bromide (FKK) on canine tracheal preparations "in vivo" and "in vitro".
In tracheal preparations of dogs anesthetized with pentobarbital, the bronchodilating activity and selectivity of FKK were compared with those of aminophylline and isoproterenol. When administered by either the i.a., i.v. or i.d. route in blood-perfused or nonperfused tracheal preparations, FKK produced a dose-dependent and long-lasting tracheal dilatation through all the administration routes, but unlike aminophylline and isoproterenol it hardly affected systemic blood pressure (SBP), heart rate (HR) and tracheal blood flow (TBF). The ability of i.a. and i.v. FKK to reduce the tracheal intraluminal pressure (ILP) (bronchodilation) by 50% (ED50), was approximately 5.4-6.2 times more potent than aminophylline and 1/3000-1/4500 as potent as isoproterenol. In the isolated canine tracheal preparations contracted with carbachol, the relaxing action produced by FKK was 1/60 and 10 times as potent as those caused by isoproternol and aminophylline, respectively. FKK has neither anti-cholinergic, ganglion blocking, alpha-adrenergic blocking nor beta-adrenergic stimulating properties. Acute lethal toxicity of FKK determined in rats by the oral route was considerably less than that of aminophylline.
D000109:Acetylcholine / Q000494:pharmacology; D000628:Aminophylline / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001993:Bronchodilator Agents / Q000494:pharmacology*; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology; D004285:Dogs; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007191:Indazoles / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D011720:Pyrazoles / Q000494:pharmacology*; D051381:Rats; D014132:Trachea / Q000187:drug effects*
D001993:Bronchodilator Agents; D007191:Indazoles; D011720:Pyrazoles; D000628:Aminophylline; D004246:Dimethylphenylpiperazinium Iodide; C037569:2,3-dihydro-7-methyl-9-phenyl-1H-pyrazolo(1,2-a)indazolium; D007545:Isoproterenol; D000109:Acetylcholine; D009638:Norepinephrine