Development of benzodiazepines for out-of-hospital management of seizure emergencies.

Management of seizure emergencies substantially changed after the introduction of rectal diazepam in Europe in the 1970s and in the United States in the 1990s. Although safe and effective, social objections and legal concerns have limited use of rectal diazepam products in out-of-hospital treatment of seizure emergencies. Shortly after the introduction of Diastat (diazepam rectal gel), commercial development of innovative formulations began involving several benzodiazepines and routes of administration, including buccal, IM, nasal, and subcutaneous. All benzodiazepines have the same mechanism of action; however, there are major differences in physicochemical properties and pharmacokinetic characteristics, which affect the choice of drug and route. This article highlights some of those differences and their effect on selection of therapies for treating seizure emergencies. We also present results from key clinical studies of these drugs and provide an update on current status of new products under development.