How do benzodiazepines work?

Benzodiazepines are commonly used by doctors; examples include diazepam (Valium) and midazolam.

Benzodiazepines are classically remembered as having three main effects:

• Sedation
• Anxiolysis (reducing anxiety)
• Muscle relaxation

The difference between sedation and anxiolysis can be difficult to appreciate. Anxiolytics are used in anxiety disorders, like panic attacks, where they greatly reduce the symptoms. 'Sedation' refers more to a general dimming of cognitive function and awareness. For example, in extreme pain (e.g. extensive burns) or with cerebral oedema (brain swelling), it may be useful to sedate the patient. Psychotic patients also require sedation in this manner.

But how do they work? Let's start from the basics and work our way up.

Neurones (nerve cells; 'neurons' in American spelling) communicate with each other by means of neurotransmitters. These are substances that one neurone secretes into a tiny space between itself and the next neurone, called the synaptic cleft. On the receiving neurone's side of the synaptic cleft are neurotransmitter receptors that take the message in.

Now neurotransmitters can make a neurone either more or less likely to fire. 'More likely' neurotransmitters work by increasing the voltage of the inside of the cell. If the cell's inner voltage becomes positive enough, the nerve fires, sending an electric message all the way to its tip (axon), which promptly releases its own neurotransmitter to the next neurone. And so on, making elaborate circuits.

Amongst the 'become less likely to fire' neurotransmitters that can be sent, the major one is what is known as GABA. If you're interested in what that stands for, there's something deeply wrong with you, but I'll mention it anway: Gamma-Amino Butyric Acid.

GABA works by opening up a chloride channel into the neurone. Basically this is like opening up a little window that chloride (alone) can pass through, going either in or out the cell. As it happens, the chloride concentration is higher outside the cell than inside, and therefore if there is free passage either way, more chloride comes in than goes out.

Since chloride is a negatively charged ion (Cl-) , more of it coming in means that the cell's becomes more negative inside. But a neurone will only fire if it becomes sufficiently positive, remember? Therefore, opening up a chloride channel makes the cell less likely to fire. We say that the cell has become hyperpolarised.

Are you keeping up? Finally, we come to benzodiazepines. These bind to benzodiazepine receptors, which are complexed with the GABA receptors. When the bezodiazepine molecules bind, they change the shape of the GABA receptor in such a way that it is becomes exceptionally attractive to GABA (neurotransmitter) molecules floating in the synaptic cleft. Suddenly, they are more likely than before to bind to their receptors, and less likely to leave. Scientists call this an 'increased affinity'.

And, with GABA having an increased affinity to bind to its receptor, more chloride channels are opened, and the cell becomes hyperpolarised and less likely to fire.

And, by hyperpolarising neurones, benzodiazepines bring about their effects. Somehow. Seriously, no one really knows how.