MOLECULAR MECHANISMS IN THE RECEPTOR ACTION OF BENZODIAZEPINES

An action that clearly distinguishes benzodiazepines from other psychotropic agents is their ability to increase the behavioral output that is depressed by response-contingent punishment or conditioned fear. This specific action has been very useful to establish screening procedures for anxiolytics but has created a number of barriers for studies of the mode of action of benzodiazepines at the molecular level. The traditional classification of benzodiazepines as anxiolytics does not take into account important pharmacological effects such as the myorelaxant and anticonvulsant action. Therefore it fails to underline that a most relevant behavioral and pharmacological effect of benzodiazepines, which clearly distinguishes them from other psychoactive agents, is the lack of sedative effects for anxiolytic doses. In fact, benzodiazepines in doses that cause the specific increase in punished behavior increase rather than reduce motor activity. The appearance of a large group of benzodiazepine analogues that associate a number of diversified behavioral effects to the antianxiety action has prompted an attempt to define the different benzodiazepines according to their mechanism of action rather than operationally. The present review is an account of the progress made in this effort, but a classification of benzodiazepines based on their molecular activity on transmitter mechanisms is not yet available.