Interaction of Atropine with the Muscarinic Receptor

WE report here the crystal structures of two muscarinic antagonists of acetylcholine, (−)-( S )-hyoscine hydrobromide 1 and (−)-( S )-hyoscyamine hydrobromide (atropine). Correlation of these two structures and that of quinuclidinyl benzilate hydrobromide 2 shows marked similarities among the three molecules although they are subjected to very different crystal packing forces. This suggests that intramolecular forces impose a preferred conformation on many such antagonist molecules. The structural correlations may be used to derive a set of rules for predicting the conformation relevant to muscarinic antagonism of acetylcholine for many molecules which at first sight are rather dissimilar to atropine (T. J. P., in preparation).