PHARMACOLOGIC POTENCY AND SELECTIVITY OF A NEW BRONCHODILATOR AGENT, 2, 3-DIHYDRO-7-METHYL-9-PHENYL-1H-PYRAZORO [1,2-A] INDAZOLIUM BROMIDE (FKK) ON CANINE TRACHEAL PREPARATIONS INVIVO AND INVITRO

  • 1 January 1983
    • journal article
    • research article
    • Vol. 262  (1) , 150-163
Abstract
In tracheal preparations of dogs anesthetized with pentobarbital, the bronchodilating activity and selectivity of FKK [2,3-dihydro-7-methyl-9-phenyl-1H-pyrazoro[1,2-a]indazolium bromide] were compared with those of aminophylline and isoproterenol. When administered by either the i.a. [intraarterial], i.v. or i.d. [intradermal] route in blood-perfused or non-perfused 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 isoproterenol 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.