Some pharmacological properties of the false cholinergic transmitter acetylpyrrolidinecholine and its precursor...

The acetylchline analogue acetylpyrrolidinecholine as well as the choline analogue pyrrolidinecholine were synthesized and the cholinergic properties of both substances were investigated on the guinea-pig ileum, rat blood pressure and frog rectus abdominis muscle. Acetylpyrrolidinecholine was 3-5 times less potent than acetylcholine on the three preparations tested. The dose-response curves to acetylpyrrolidinecholine were shifted to the right in a parallel manner by atropine and (+)-tubocurarine. The dissociation constants for atropine and (+)-tubocurarine obtained with acetylpyrrolidinecholine as agonist were not different from those obtained with acetylcholine. This indicates that acetylpyrrolidinecholine specifically stimulates muscarine and nicotine receptors. Eserine potentiated the effects of acetylcholine more than those of acetylpyrrolidinecholine. Pyrrolidinecholine was only a weak agonist on the guinea-pig ileum. It caused a rise of rat blood pressure in doses higher than 10 mumol per rat. Neuromuscular transmission of the phrenic nerve-diaphragm preparation of the rat was not impaired during a 150 min incubation period with 1 mM pyrrolidinecholine. It is suggested that the possible formation and release of acetylpyrrolidinecholine as a false cholinergic transmitter does not modify neuromuscular transmission in skeletal muscle.