Effect of atropine and DMAE (a hemicholinium derivative) on contractile responses of the guinea pig ileum

A close structural analogue of hemicholinium, α,α′-bis(dimethylammoniumacetaldehyde diethylacetal)-p,p′-diacetylbiphenyl bromide (DMAE), was reported to antagonize responses to ganglionic stimulants more than responses to preganglionic nerve stimulation in the cat or dog and to possess activity both similar to and different from cocaine. The present study was concerned with the effect of DMAE and atropine on the response of the isolated guinea pig ileum to ganglionic stimulants and to transmural stimulation. Nicotine and DMPP, ganglionic stimulants, caused initial spike-like contraction, which was blocked by atropine, followed by a slow sustained contraction, which was atropine-resistant but was inhibited by DMAE. Cocaine and morphine, unlike DMAE, did not elicit a differential antagonism of the biphasic effects of the ganglionic stimulants. Contractions evoked by transmural stimulation were, however, augmented by DMAE but reduced by cocaine and atropine. DMAE could induce contractions of the ileum, by means of intrinsic excitation of the cholinergic neuronal elements and not by a direct action on cholinergic smooth muscle receptors. In conclusion, ganglionic stimulants have revealed in the guinea pig ileum an atropine-resistant noncholinergic neuronal pathway which was sensitive to DMAE blockade. Furthermore, actions of DMAE and cocaine on contractions caused by ganglionic stimulants and transmural stimulation were found to be nonparallel.