A STUDY OF THE PERIPHERAL AND CENTRAL ACTIONS OF DIBROMOPYRUVIC ACID

¹ Department of Pharmacology, University of Illinois College of Medicine, Chicago

Two actions of dibromopyruvic acid have been differentiated in vivo and in vitro; it produces a wide variety of cholinergic effects and is also toxic to all tissues and organ systems studied. The toxic effects have been related to its inhibitory action on oxidative metabolism. The in vivo and in vitro evidence indicates that dibromopyruvic acid produces its cholinergic activity by reacting with cholinergic receptors and that its anticholinesterase activity plays only a contributory role. Dibromopyruvic acid has been characterized as a drug with predominantly muscarinelike activity. It has been differentiated from muscarinelike drugs by its failure to produce bradycardia. Its actions on the central nervous system are similar to the actions of acetylcholine mind anticholinesterases (as reported by other investigators). Because it possesses predominantly muscarinelike peripheral activity, its action on the central nervous system has been interpreted as evidence for the existence of nonnicotinic cholinergic synapses in the central nervous system. Atropine was ineffective in antagonizing the spinal cord activity of dibromopyruvic acid, while mephenesin was an effective antagonist. These observations have suggested that there are nonnicotinic cholinergic interneurones that are not depressed by atropine.