Soft drugs. 3. A new class of anticholinergic agents

• Published in: Journal of medicinal chemistry Vol. 23; no. 5; pp. 474 - 480
• Main Authors: Bodor, Nicholas, Woods, Ross, Raper, Colin, Kearney, Pauline, Kaminski, James J
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 01.05.1980
• Subjects: Acetylcholine - antagonists & inhibitors; Animals; Atropine - pharmacology; Blood Pressure - drug effects; Cats; Chemical Phenomena; Chemistry; Guinea Pigs; Hydrolysis; In Vitro Techniques; Kinetics; Muscle Contraction - drug effects; Muscle, Smooth - drug effects; Parasympatholytics - chemical synthesis; Parasympatholytics - metabolism
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm00179a002

A new class of antimuscarinic drugs was designed and synthesized. The compounds are "soft" quaternary ammonium esters in which there is only one carbon atom separating the ester oxygen and the quaternary head. The compounds are potent anticholinergics when derived from hindered "umbrella" acids and cholinergics when derivatives of simple aliphatic acids. The more potent anticholinergics have up to 10 times higher acetylcholine antagonist activity than atropine, but they have a much shorter duration of action. The compounds cleave hydrolytically with simultaneous destruction of the quaternary head. The compounds are promising as selective, local agents, particularly as inhibitors of eccrine sweating.