Effects on tracheal smooth muscle of adenosine and methylxanthines, and their interaction

Abstract
The relaxant effects of xanthine and 15 different methylxanthines were studied in a guinea-pig isolated tracheal ring preparation. Substitution in the 3- and 1-positions of the xanthine molecule were found to be of greatest importance for improving tracheal relaxant potency. The unsubstituted xanthine and all 9-methylated xanthines were weakly active. Adenosine occasionally contracted (slightly) the tracheae but a concentration-dependent relaxation was always recorded. Endogenous adenosine did not seem to contribute to the tracheal tone. Xanthines methylated in the 1-position consistently antagonized the relaxant effect of adenosine and produced graded rightward shifts of the concentration-response line to adenosine (competitive antagonism). Xanthines with an unsubstituted 1-position or with comethylation in the 9-position were generally without antagonism. The results support our view that bronchodilating xanthine derivatives lacking universal adenosine antagonism can be produced.

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