The Biological Basis of Benzodiazepine Actions

In spite of intensive research during the decade following the introduction of chlordiazepoxide into clinical medicine, the mechanism(s) of actions of benzodiazepines remained obscure. An important breakthrough occurred with the discovery of the role of gamma -amino-butyric acid (GABA) as the main inhibitory neurotransmitter in the mammalian central nervous system (CNS). Demonstration that there was a close association between benzodiazepine actions and GABAergic mechanisms (Polc, Mohler & Haefely, 1974; Costa, Guidotti & Mao, 1975; Haefelyet at., 1975) led to massive amounts of research which clarified the relationship between GABA and benzodiazepines and resulted in a number of fundamental neurochemical discoveries. This chapter reviews current understanding of the biological basis of benzodiazepine actions and builds on earlier comprehensive reviews (Haefely, 1977, 1978, 1980, 1983b; Haefelyet al., 1975, 1978, 1981, 1983a).