Effects of cularine and other isoquinoline alkaloids on guinea-pig trachea and human bronchus.

The relaxant effects of the isoquinoline alkaloids, cularine, antioquine, obaberine and 6, 7-dimethoxy-1, 2, 3, 4-tetrahydroisoquinoline, with structures related to that of papaverine, have been studied on the guinea-pig isolated trachea and human bronchus against contractions induced by acetylcholine (ACh), histamine, neurokinin A (NKA) and KCl. These effects were compared with those of papaverine and theophylline. Among the alkaloids tested, the most potent was cularine, the relaxant activity of which, in terms of pD2, was between those of papaverine and theophylline. The results showed that for the guinea-pig isolated trachea and the human bronchus, the cularine concentrations required to inhibit K(+)-induced contractions were close to those necessary to counteract ACh-, histamine- and NKA-induced contractions. The relaxant activity of cularine was not modified when it was tested on tracheal preparations under resting tone or after epithelium removal. In addition, cularine was able to inhibit Ca2(+)-induced contractions in a Ca2(+)-free, K(+)-enriched solution at the same concentrations as those which inhibited the action of the different contractile agents in normal Krebs solution. All these data show that cularine displays non-specific antispasmogenic activity on guinea-pig and human airways. The lower relaxant activity (pD2) of cularine compared with papaverine suggests the importance of free rotation of the isoquinoline-benzyl ring linkage as well as of the degree of hydrogenation of the heterocyclic ring in the spasmolytic effects of isoquinoline compounds.