Non-competitive spasmolytics as antagonists of Ca++-induced smooth muscle contraction

The spasmolytic drugs papaverine, phenpropamine, Cxn 2 (1-methyl-amino-3,3,5-trimethylcyclohexane), khellin, cyclandelate, magnesium chloride, cocaine, 2,4-dinitrophenol and KCN antagonize various types of spasmogens, such as acetylcholine or histamine, non-competitively. They are assumed to act at some level in the excitation-contraction process common to the various spasmogens. Ca++ is essential for the induction of a contraction by the spasmogens. In the non-competitive action of some spasmolytics, Ca++ is postulated to be involved. To detect possible differences in their mechanism of action the various spasmolytics were tested against Ca++ acting as a pseudo-spasmogen on the K+-primed taenia caeci of the guineapig in a Ca++-free medium. Although different mechanisms of action for the various spasmolytics are to be expected, they all behaved similarly with respect to Ca++ in that they all caused a parallel shift in the log dose-response curve of Ca++ to higher concentrations.