Offset rate of action of muscarinic antagonists depends on their structural flexibility

Summary Time course measurements of the action of muscarinic antagonists were performed in the spontaneously beating carp atrium. Several high affinity drugs, which embody the quinuclidine structure were examined. The structural flexibility of these molecules was reflected in the dissociation of the drugs from the muscarinic receptor. The dissociation of rigid drugs was very much prolonged as compared to flexible drugs of the same affinity.We thank Prof. S. Lifson for helpful discussion and Mrs M. Bendikovsky for technical assistance. This work was supported by a USA-Israel Binational Science Foundation (BSF-Jerusalem) grant to Y. Lass.