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  • Title: Evaluation of the novel potassium channel activator BRL 55834 as an inhaled bronchodilator in guinea-pigs and rats: comparison with levcromakalim and salbutamol.
    Author: Arch JR, Bowring NE, Buckle DR.
    Journal: Pulm Pharmacol; 1994 Apr; 7(2):121-8. PubMed ID: 8081072.
    Abstract:
    The novel potassium channel activator BRL 55834 and the prototype compound levcromakalim have been compared as inhaled bronchodilators in guinea-pigs and rats. Salbutamol was included in the guinea-pig studies. In anaesthetized guinea-pigs, inhaled BRL 55834 [ED50 = 0.9 (0.5-1.5) micrograms per animal] was equipotent with salbutamol and about tenfold more potent than levcromakalim as an inhibitor of the increase in airways resistance in response to iv histamine. In anaesthetized rats, BRL 55834 [ED50 = 0.5 (0.4-0.7) micrograms] was about eightfold more potent than levcromakalim in inhibiting the response to inhaled methacholine. BRL 55834 had no effect on blood pressure in anaesthetized guinea-pigs or rats, whereas levcromakalim lowered blood pressure in rats at a dose level that had less effect on the airways than one tenth of the highest dose of BRL 55834 used. In conscious guinea-pigs, BRL 55834 (ED100 = 5 micrograms) was twice as potent as levcromakalim and one sixth as potent as salbutamol in delaying the onset of dyspnoea in response to inhaled histamine. In each model each compound was effective at the earliest time studied, but the peak effect of BRL 55834 tended to be delayed and it was longer acting than levcromakalim or salbutamol. Thus inhaled BRL 55834 is a potent bronchodilator, with a rapid but prolonged duration of action that lacks significant systemic vascular activity.
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