Answer: Benzodiazepines act at a special site on the GABA receptor to function as a positive allosteric modulator, increasing the action of GABA.
http://www.wikidoc.org/index.php/Benzodiazepine
Pharmacodynamics of benzodiazepines
Benzodiazepines (or benzos, BZDs, or BDZs for short) are a commonly prescribed class of drugs which can induce a relief of anxiety, muscle relaxation, and prevention of seizures for people with epilepsy. It also can induce some amnesic effects and sedation, making it useful during surgery. Some of the more common drugs in this class include Valium, Xanax, and Ativan.
The main mechanism of action of benzodiazepines are positive allosteric modulators, or PAMs. More specifically, benzodiazepines are PAMs for the GABA receptor, the most common inhibitory neurotransmitter in the brain. Positive allosteric modulators increase the action of GABA. 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.
Pharmacokinetics of benzodiazepines
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 better 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 of benzodiazepines and withdrawal
Benzodiazepines have a risk for dependence after chronic use. In people who regularly use benzodiazepines, they may experience the symptoms of withdrawal. Some of the most often reported symptoms of benzodiazepine withdrawal include:
Sleep difficulty and insomnia
Increased anxiety and irritability
Cognitive deficits, including memory loss and difficulty concentrating
In severe cases, non-epileptic seizures and manic episodes
It is theorized these withdrawal symptoms are due to pharmacological changes that the body makes while the person is taking the drug, which can lead to receptor level homeostatic adaptations. (GABAA receptor subtypes and benzodiazepine use, misuse, and abuse)
Additionally, long term use also seems to be associated with an increased risk for suicide.
