Lorazepam is a benzodiazepine that works through activation of GABAA to increase the activity of GABA which in turn reduces neuronal firing in the brain.
The metabolism of lorazepam is different than other benzodiazepines as it is metabolized in the liver by the process of glucuronidation. There are two other benzodiazepines metabolized in this fashion and they are temazepam and oxazepam. The useful pneumonic “LOT” can help you to remember which benzodiazepines are metabolized through glucuronidation. Glucuronidation is when a glucuronic acid is added to a substrate from UDP-glucuronic acid via a UDP glucuronosyltransferase. The interesting and important fact about the benzodiazepines that are metabolized through glucuronidation is that there are no active metabolites and they are rarely susceptible to drug-drug interactions unlike other benzodiazepines such as midazolam and diazepam that are metabolized through the Cytochrome P450 (microsomal oxidation) pathway and potentially have many more drug-drug interactions.
Defined by: Lauren G. Powlovich, MD