The smooth muscle relaxant effects of the novel
potassium channel opener,
HOE 234, were investigated in guinea pig airways and compared with those of
lemakalim (
BRL 38227). Both agents evoked concentration-related reduction in spontaneous tracheal tone or in the tone induced by
histamine,
prostaglandin E2 or
carbachol.
HOE 234 was more potent, particularly against
carbachol, and was considerably longer acting than
lemakalim in a wash-out experiment. On testing for preventive efficacy against
histamine-induced bronchoconstriction in anaesthetized animals a dose-related decrease of pulmonary resistance (RL) was observed.
HOE 234 given either intravenously (i.v.) or by inhalation was longer acting and 3 and 6 times more potent than
lemakalim. Administration of 30 micrograms/kg i.v.
HOE 234 during continuous bronchoconstriction maintained by infusion of
histamine decreased RL for more than 20 min whereas the effect of 100 micrograms/kg i.v. lemakalin disappeared within 4 min. These results show that
HOE 234 is effective against contractile response induced by
asthma mediators in guinea pig airways and compares favourably with
lemakalim. Moreover it acts on acute existing
bronchospasm and therefore has the potential to act against
asthma attacks.