Pharmacological studies in animals of beta-hydroxyethyltheophylline, the major metabolite of doxofylline in humans.
beta-HET (beta-Hydroxyethyltheophylline), the major metabolite of the antibronchospastic, antiasthmatic drug doxofylline was studied in several in vitro and in vivo trials to characterize its pharmaco-toxicological profile. When compared to the parent compound, beta-HET was found to be significantly less active. It was also discovered to be a very weak inhibitor of phosphodiesterase activity. Its affinity for A1- and A2-adenosine receptors was even lower than that of doxofylline, which was quite low. The oral toxicity of beta-HET was about three times lower than that of doxofylline. The pharmacological activity of doxofylline is due to the drug in its original form and not to its major metabolite.
Franzone
J S
JS
Istituto Biologico Chemioterapico ABC S.p.A., Research Laboratories, Torino, Italy.
Cirillo
R
R
Reboani
M C
MC
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000187:drug effects; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000996:Antitussive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D001986:Bronchial Spasm / Q000188:drug therapy; D001993:Bronchodilator Agents / Q000494:pharmacology*; D004562:Electrocardiography / Q000187:drug effects; D004837:Epinephrine / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D007082:Ileum / Q000187:drug effects; D007928:Lethal Dose 50; D008297:Male; D009068:Movement / Q000187:drug effects; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D011817:Rabbits; D051381:Rats; D011983:Receptors, Purinergic / Q000378:metabolism; D012701:Serotonin / Q000494:pharmacology; D013268:Stimulation, Chemical; D013806:Theophylline / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000097:blood / Q000494:pharmacology / Q000633:toxicity; D014132:Trachea / Q000187:drug effects; D014630:Vagus Nerve / Q000187:drug effects
D000996:Antitussive Agents; D001993:Bronchodilator Agents; D011983:Receptors, Purinergic; D012701:Serotonin; D013806:Theophylline; D015105:3',5'-Cyclic-AMP Phosphodiesterases; C008749:etofylline; C029797:doxofylline; D000109:Acetylcholine; D004837:Epinephrine