Action of some purin derivatives on the isolated bronchus

Abstract

In connection with a study of the effects of various drugs on the isolated bronchi of pigs the authors studied a number of purin derivatives. The effects of caffein or trimethyl xanthin in doses of 1-20 mgm. in 25 c.c. of Locke's solution gave the following results; small doses produced no effect on bronchial muscle or occasionally a very slight constriction. After large doses of caffein a little relaxation of the normal bronchial preparations was noted. When, however, such bronchial preparations were first brought into a state of high tonus or contraction, as for instance on treatment with muscarin, the relaxing effect of a subsequent dose of caffein was much more marked. On the whole, however, the results obtained indicated that caffein has a very weak dilator effect on the bronchus.

Following experiments with caffein, observations were made on the effects of theobromin or 1-3 dimethyl-xanthin and theocin or 3-7 dimethyl-xanthin. It was found that both dimethyl-xanthins produced much greater broncho-dilatation than trimethyl-xanthin or caffein. The authors were unable to obtain a mono-methyl xanthin but they did study the effects of xanthin itself. Although xanthin is very slightly soluble nevertheless even very minute quantities of the substance (1 c.c. of 1-200,000 solution) introduced into 25 c.c. of Locke's solutions in which the preparation was suspended were found to produce a very marked relaxation. Hypoxanthin acted in the same way. Going a step further experiments were made with minute quantities of guanidin and adenin and both of these were found to produce relaxation of the bronchus and seemed to be comparatively more potent even than xan thin. Passing to the nucleosid guanosin, the pharmacological action became different. Guanosin produced no effect. A few experiments with adenin nucleotid showed that it also was inactive.