The Bronchodilator Activity of AY-22093, a Prostanoic Acid Derivative

Abstract

The bronchodilator activities of AY-22093, prostaglandin E2 (PGE2), and isoproterenol were compared using in vivo and in vitro techniques. In the conscious guinea pig, an aerosol of AY-22093, PGE2, and isoproterenol afforded significant protection against histamine-induced bronchospasm; AY-22093 and isoproterenol were equally effective in protecting against antigen-induced anaphylaxis. In the anesthetized guinea pig, using the Konzett and Rössler technique, PGE2 (1 μg/kg, intravenously (i.v.)) inhibited the bronchoconstriction induced by histamine (10 μg/kg, i.v.) by 63% as compared with 37% inhibition after AY-22093 (1 μg/kg, i.v.). Larger intravenous doses of PGE2 and AY-22093 (10 and 20 μg/kg) caused almost complete inhibition of the histamine-induced bronchoconstriction. The administration of PGE2 (0.5–10 μg) or AY-22093 (5–100 μg) by aerosol inhibited the bronchoconstriction induced by histamine (10 μg/kg, i.v.) by 20–70%. Maximum bronchodilator effects occurred within 3 min and lasted for as long as 30 min after either route of administration. Both compounds caused a fall in blood pressure after intravenous but not after aerosol administration. AY-22093 relaxed the guinea pig tracheal strip where tone was induced by carbachol. This relaxation was not altered by propranolol. The results indicate that AY-22093 is a bronchodilator qualitatively similar to PGE2, having a direct effect on smooth muscle but less potent than PGE2.