In addition to a distinct binding site for the neurotransmitter GABA, the GABAa receptor has a second recognition site at which certain drugs can bind. In 1957, quite by accident, scientists at a drug company discovered that an unknown compound reduced fear in animals. When tested on humans with anxiety disorders, this drug, called Librium, was found to be a powerful tranquilizer. Since then, many other drug companies have made minor chemical changes in the structure of Librium, producing a large number of similarly-shaped drugs called Benzodiazepines. Two well known Benzodiazepines are Valium and Xanax, tranquilizers which work to reduce fear and anxiety.
Because they do not bind to the GABA recognition site, the Benzodiazepines do not work as directly as GABA in allowing the free passage of chloride ions through the pore of the receptor. Instead, when a drug like Valium of Xanax binds to its specific recognition site, the 3-dimensional shape of the GABAa receptor changes in such a way as to allow GABA to bind more easily to its own binding site. Increased GABA-binding leads to an increased influx of choride ions at the post-synaptic cell. Whether this increase in chloride influx is due to an increase in the amount of time that the channel stays open, or to a greater affinity for the GABA molecule at its binding site is not currently known. It is, however, clear that increased chloride influx causes an increased number of inhibitory inputs (IPSPs) at the post-synaptic neuron. This increase in IPSPs makes it difficult for any excitatory inputs (EPSPs) to cause an action potential in the post-synaptic cell. When the excitatory signals caused by fear or stress are inhibited in this way, the result is a marked decrease in anxiety and a greater feeling of calm.