How Valium works: in detail

This week, in Nature, the structure of a very important neurotransmitter receptor was revealed. The receptor, the GABA-A, allows the functioning nervous system to avoid the “brain super storms” that constitute epileptic seizures. When the neurotransmitter, GABA, binds to GABA-A, in synapses, in acts to inhibit neural activity. The inhibition of neural activity is critical to brain function because the brain can then compute in a very meta-stable state, quite like a marble on the edge of a saddle. That is one of the key design features of our brains that perhaps can be reverse-engineered someday for more power high performance computing a great energy efficiency.

It’s not surprising then, that the GABA-A receptor is also the target for some key drugs, like Valium and alcohol. Both of these drugs act to inhibit brain activity. When taken together with opioids, the effect is one of synergy and the effects can be deadly.

The paper by Zhu et al. used a technique called cryo-electron microscopy to reveal the detailed structure of GABA-A “frozen in the moment” of binding to a Valium analog. This is very important because it may reveal design hints at how to build a future Valium-like drug that relieves anxiety without sedation.