PHARMACOLOGIC EVALUATION OF A NEW SERIES OF CHOLINERGIC ANTAGONISTS CONTAINING AN AGONIST MOIETY

¹ Departments of Pharmacology and Chemistry and Pharmaceutical Chemistry, Medical College of Virginia, Richmond, Virginia

Seven derivatives of dimethylaminoethyl benzilate ethiodide (lachesine) have been prepared and evaluated for antagonistic activity against acetylcholine and carbachol on isolated segments of rat jejunum and against histamine and phenylephrine on isolated aortic strips from rabbits. These compounds were designed to combine structural features of classical antagonists with those of the most potent muscarinic agonists in order to improve the affinity of the resulting compound for the receptor. This approach was attempted in order to provide information concerning configuration and structural requirements of agents acting on the cholinergic receptor. The present modifications did not yield an agent with augmented antagonistic activity.