Differentiation between bronchodilation and universal adenosine antagonism among xanthine derivatives.
Relaxant effects and adenosine-antagonism of 3-propyl-xanthine (enprofylline) and 10 different methyl-xanthines were examined in isolated guinea-pig tracheas. The chemical structural requirements for tracheal relaxation were found to be different from those for adenosine antagonism by the xanthine derivatives. All xanthines produced relaxation: Enprofylline was about 5 times more potent than theophylline. However, only xanthines with a methyl in the 1-position consistently antagonized the relaxant effect of adenosine. --Theophylline over a wide range of concentrations (30-900 microM) produced a concentration dependent and surmountable antagonism at nervous adenosine receptors (isolated guinea-pig myenteric-plexus preparations). The same concentrations of enprofylline were almost devoid of antagonism at these adenosine receptors. In mice theophylline (6-24 mg/kg given intraperitoneally) dose-dependently increased locomotor activity while enprofylline (2-48 mg/Kg) was without effect on behaviour. "Non-blocking" xanthines such as enprofylline may be potent bronchodilators but lack many theophylline-like actions. We, therefore, forward the hypothesis that universal adenosine antagonism is both unnecessary and undesirable with xanthine antiasthmatics.
D000241:Adenosine / Q000037:antagonists & inhibitors* / Q000502:physiology; D000818:Animals; D001993:Bronchodilator Agents / Q000494:pharmacology*; D004176:Dipyridamole / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D006801:Humans; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009197:Myenteric Plexus / Q000187:drug effects; D011956:Receptors, Cell Surface / Q000187:drug effects*; D011983:Receptors, Purinergic; D013806:Theophylline / Q000008:administration & dosage / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects; D014970:Xanthines / Q000494:pharmacology*
D001993:Bronchodilator Agents; D011956:Receptors, Cell Surface; D011983:Receptors, Purinergic; D014970:Xanthines; D004176:Dipyridamole; D013806:Theophylline; C034347:enprofylline; D000241:Adenosine