DIMENSIONS OF THE ION CHANNEL IN NEURONAL NICOTINIC ACETYLCHOLINE-RECEPTOR AS ESTIMATED FROM ANALYSIS OF CONFORMATION-ACTIVITY RELATIONSHIPS OF OPEN-CHANNEL BLOCKING-DRUGS

Relationship between the size of the molecule in the series of organic ions Et3N-(CH2)5-NR1R2R3 (R(i) - alkyl or cycloalkyl substituents) and their abilities to block nicotinic acetylcholine receptors (AChRs) due to their open-channel blockade in the neurons of autonomic ganglia and in frog end-plate was analyzed. All low-energy equilibrium conformations of the drugs were calculated by the molecular mechanics method. A unique rectangular channel profile 6.1 x 8.3 A. for which the best correlation between blocking activity of the drugs and total population of their conformations being able to penetrate into the channel, was deduced from all those tested.