Acid-catalyzed ethanolysis of temazepam in anhydrous and aqueous ethanol solutions

Article abstract of DOI:10.1002/jps.2600830628

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.