Today, γ-aminobutyric acid (GABA) is recognized as the most important inhibitory neurotransmitter in the mammalian CNS comprising 40% of inhibitory synaptic processing. As its receptor GABAA is largely responsible for effects of alcohol, it can be argued that it is one of the oldest drug targets known.

In the 1870s, chloral hydrate, whose metabolite modulates the GABA receptor complex, was widely used as a sedative and as a treatment for insomnia. Although effective, abuse and dependence were major issues and by the 1920s its use had been almost entirely supplanted by the barbiturates which work on the GABAA receptor.

Unfortunately, it soon became apparent that barbiturates also carry the risk of abuse, dependence, severe withdrawal symptoms, and lethal overdose. Although still used in some situations, the barbiturates were replaced by benzodiazepines with the advent of Librium in 1960. By the late 1970s, benzodiazepines were the most commonly prescribed drugs in the world.