Inhibition of intestinal smooth muscle function by tamoxifen and clomiphene

The acute in vitro effects of the oestrogen antagonists clomiphene (a racemic mixture) and tamoxifen were examined upon spasmogen induced contractions of the guinea pig ileum. Both oestrogen antagonists inhibited the contractions produced by acetylcholine, the muscarinic agonist beta-methylcholine, histamine and bradykinin in a manner which suggests non competitive antagonism. Concentration effect curves to each of the spasmogens were unaffected using 0.1 mumoles/litre of either of the oestrogen antagonists. Clomiphene at 1 mumole/litre reduced the maximum response to the spasmogens by 20 to 50%. Tamoxifen at the same concentration also inhibited the contractions but to a much smaller extent. Clomiphene at the highest concentration tested 10 mumoles/litre completely suppressed contractions to all the spasmogens. Tamoxifen at 10 mumoles/litre completely suppressed contractions to beta-methylcholine and bradykinin. A residue of a response to acetylcholine and histamine remained and this was abolished by raising the concentration to 100 mumoles/litre. The data indicated that clomiphene was more potent than tamoxifen upon the inhibition of the contractions of the ileum. The results demonstrate a non specific effect of the oestrogen antagonists upon smooth muscle function and do not substantiate early reports of specific anticholinergic activity. The possibility of these effects contributing to both the side effects and the antitumor activity of the oestrogen antagonists is discussed.