Sensitization of contracted tracheal smooth muscle to beta-adrenergic spasmolysis by subthreshold doses of papaverine.

In certain cases beta-adrenergic substances cause little or no relaxation of tracheal or bronchiolar smooth muscles contracted by spasmogenic mediators. This phenomenon is explained on the basis of the model of functional antagonism, with the suppositions that the spasmogenic system has a reserve and the spasmogen concentrations are much higher than the concentration which would cause a just-maximal contraction. If this is correct, the model predicts that it should be possible to restore the effectiveness of the beta-adrenergic spasmolytics with low doses of a non-competitive (metactoid) spasmolytic, provided that this substance acts by depressing the subeffect curve. Such a metactoid antagonist should cause the desired result in subthreshold concentrations, i.e. concentrations which as such do not cause relaxation of the contracted muscles. In a series of experiments on the isolated tracheal chain of the guinea-pig the results agreed with this expectation. This provides additional proof for the model of functional interaction and suggests that the combination of beta-adrenergics with low doses of a metactoid spasmolytic may be of clinical interest.