Acid-catalyzed ethanolysis of temazepam in anhydrous and aqueous ethanol solutions.
The benzodiazepines are a family of anxiolytic and hypnotic drugs. When taken concurrently with ethanol, a pharmacological interaction may occur, potentiating the central nervous system depression produced by either drug. In addition to this pharmacological interaction, this report describes a novel chemical reaction between temazepam (a 3-hydroxy-1,4-benzodiazepine) and ethanol under acidic conditions similar to those found in vivo, resulting in a 3-ethoxylated product. Optimal conditions, kinetics, equilibrium, and the mechanism of this acid-catalyzed ethanolysis are reported. The results raise the possibility that the ethanolysis reaction may occur in the stomach of people who consume alcohol and 3-hydroxy-1,4-benzodiazepine on a regular basis. The acid-catalyzed ethanol-drug reaction is a relatively unexplored area and may alter the pharmacological action of some drugs.
Yang
S K
SK
Department of Pharmacology, F. Edward Hébert School of Medicine, Uniformed Services, University of the Health Sciences, Bethesda, MD 20814-4799, USA.
D014151:Anti-Anxiety Agents / Q000378:metabolism*; D004347:Drug Interactions; D000431:Ethanol / Q000378:metabolism*; D006868:Hydrolysis; D007700:Kinetics; D013693:Temazepam / Q000378:metabolism*
D014151:Anti-Anxiety Agents; D000431:Ethanol; D013693:Temazepam