On the biochemical mechanism of action of 1-propyl-3-methyl-7-(5-hydroxy-hexyl)-xanthine (HWA 153), a new bronchospasmolytically active methyl xanthine derivative.
1-Propyl-3-methyl-7-(5-hydroxy-hexyl)-xanthine (HWA 153) is a new bronchospasmolytic agent with a significant influence on the cAMP system of lungs and bronchi. In in vitro experiments HWA 153 inhibits cAMP phosphodiesterase (PDE) isolated from bovine bronchi more than does theophylline. HWA 153 is (in conc. 5 x 10(-4) mol/l) 1.8 and 4.3 times more active as a PDE inhibitor of guinea pig lungs and bronchi, respectively, than theophylline-ethylenediamine. HWA 153 also stabilizes rat erythrocyte membrane against hypoosmotic shock. In isolated guinea pig bronchi HWA 153 (in conc. 5 x 10(-4) mol/l) decreases by 77% bronchial spasm induced by the addition of histamine (5 x 10(-5) mol/l). A significant increase in cAMP level of bronchi was simultaneously observed. In in vivo experiments HWA 153 (25 mg/kg p.o.) inhibits PDE of lungs and bronchi of guinea pigs. Simultaneously, a significant increase in cAMP level in these organs was observed. In in vivo experiments with hypoxic rats, HWA 153 (25 mg/kg p.o.) increases ATP, ATP/ADP ratio and adenylate energy charge (AEC) in hypoxic rats, 1 h after administration. This indicates a positive influence of HWA 153 on the energy metabolism of red blood cells.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000818:Animals; D001993:Bronchodilator Agents / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D004910:Erythrocyte Membrane / Q000187:drug effects; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D000860:Hypoxia / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D051381:Rats; D014970:Xanthines / Q000494:pharmacology*
D001993:Bronchodilator Agents; D014970:Xanthines; D006632:Histamine; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases