[Cholinomimetic activity of acetylcholine and sebacinyldicholine derivatives with differing cationic group...

The intrinsic alpha activities and the D2 (frog, m, rectus abdominalis) concentrations were estimated for different acetylcholine and sebacinylcholine derivatives. So were also the A2 values for antagonists and the affinity constants Kc for some partial agonists. The results obtained disprove Paton's "rate-theory". The relationship between the cholinergic activity and the volume of cationic groups was studied and it could not possibly be explained by the steric hindrance alone. It is suggested that certain hydrophobic radicals of the cationic groups contact the receptor surface outside the anionic centre. Such contacts prevent the cholinoreceptor to change its conformation and thus inhibit the depolarization of the membrane. An approximate estimation of the anionic site dimensions is given.