What is the pharmacological site of action of benzodiazepines?

Answer: Benzodiazepines act at a special site on the GABA receptor to function as a positive allosteric modulator, increasing the action of GABA.



Benzodiazepines are a commonly prescribed class of drugs which can induce a relief of anxiety, muscle relaxation, and prevention of epileptic seizures. It also can induce some amnesic effects and sedation, making it useful during surgery. Some drugs in this class include Valium, Xanax, or Ativan.

As a positive allosteric modulator, benzodiazepines increase the action of GABA, the most common neurotransmitter in the brain. GABA is generally inhibitory in the adult brain, so while a benzodiazepine is present, there is more inhibition in various networks in the brain. Positive allosteric modulators do not compete with GABA to act on the primary GABA binding site. Instead, they bind to a unique site, and once doing so, they cause a change in formation of the ion channel. This conformational shift causes GABA to be more inhibitory, possibly through allowing more chloride ions to move through the open ion channel, or to cause the ion channel to remain open longer than normal.

The benzodiazepine drugs are cleared out of the system by metabolism. Enzymes in the liver called cytochrome P450s break down the chemicals into metabolites, some of which may also be active. There is much variability in the half life of some of these compounds. Short acting benzodiazepines have a half-life between 1 and 12 hours, making them good for treating insomnia. On the other hand, other benzodiazepines can have a half-life up to 250 hours, making them ideal for treatment of anxiety disorders.

Side effects

Benzodiazepines (or benzos for short) have a risk for dependence after chronic use. Additionally, long term use also seems to be associated with an increased risk for suicide.