The pharmacological properties of
8-hexyloxy-3-(1H-tetrazol-5-yl)-2H-chromen-2-one,
KP-136 were compared with those of an
antiallergic medicament,
disodium cromoglycate (DSCG) in experimental
asthma models.
KP-136 (0.125-1 mg/kg i.v., 0.5-2 mg/kg p.o.) produced a dose-dependent inhibition to allergic
asthma of rats and was more potent than DSCG (1-5 mg/kg i.v.).
KP-136 (1 mg/kg, i.v.) was also effective on allergic
asthma of guinea pigs, although DSCG was ineffective even at a high dose of 50 mg/kg (i.v.). In rats, both
KP-136 and DSCG significantly blocked the reduction of
histamine content of the trachea after allergic
asthma and inhibited the
antigen-induced histamine release from lung fragments (
KP-136 0.5 micrograms/ml, DSCG 50 micrograms/ml) and peritoneal exudate cells (
KP-136 0.1 micrograms/ml, DSCG 10 micrograms/ml).
KP-136 also showed relaxation activity for isolated guinea pig trachea at high doses of 2 and 5 micrograms/ml. The major mechanism of the potent
antiasthmatic activity of
KP-136 is postulated to be the blocking of bronchoactive mediator release. The relaxation of smooth muscle is also suggested to be an additive mechanism.