Mechanism

How does alprazolam (Xanax) act at receptors?

Answer: Xanax is a drug that belongs to the class of benzodiazepines that functions as a positive allosteric modulator at the GABAA receptors.

alprazolam xanax receptors GABA

Xanax is one of the most commonly prescribed and misused benzodiazepine drug in the US. It has medical use for treatment of generalized anxiety disorder, major insomnia and sleep disorders, epilepsy, and chemotherapy related nausea. However, due to the risk of addiction or dependence, Xanax is a Schedule IV rated drug under the Controlled Substances Act as set forth by the Food and Drug Administration and Drug Enforcement Agency. Between 2002 and 2012, the number of people who are seeking addiction help for Xanax abuse has increased ten fold from 3,000 to 30,000. While this indicates that there is a better infrastructure for helping those who want the help, it also likely means that Xanax abuse is rapidly rising.

The GABAA receptor is strongly expressed throughout the brain. The receptor itself has a main site of action where molecules of GABA, the inhibitory neurotransmitter can bind. This site is called the orthosteric site. Also on the receptor are different sites where the other drugs might bind. These are the allosteric sites. One allosteric site binds a class of drugs called benzodiazepines, which includes Xanax and valium, for example. These drugs potentiate the action of GABA when it binds. Drugs that modify signaling of the neurotransmitter are called allosteric modulators.

Xanax is a positive allosteric modulator, meaning that it increases signaling when molecules of GABA activate the receptor. Because GABA is almost always being released, this signaling is enhanced when Xanax is on board.

Alprazolam was first introduced into the American market in 1981. One of the major advantages of the drug for the therapy of anxiety is that it has a very rapid effect of therapy, with the anxiety generally improving within a week. Additionally, it usually shows no loss of efficacy, even after chronic use of the substance.

Behavioral consequence of Xanax

Like many other benzodiazepine drugs, Xanax is also known to cause anterograde amnesia. For example, in human studies, it was found that treatment with alprazolam for two weeks resulted in decreased scores on a Paired Associates Learning (PAL) task and a Delayed Matching to Sample (DMS) task. Both the PAL and the DMS task evaluate a person’s nonverbal visual memory, but the PAL task is also measures new learning.

In the Paired Associates Learning task, the subject looks at a screen. On the screen, there are places for 8 boxes to appear. Some of the boxes will open up in some order. Inside some of the boxes is a pattern. In the testing phase, various patterns will be shown in the center of the screen. The experimenter will then be asked which box contains the pattern. If a person’s new memory learning and recognition were impaired, they would perform worse on matching the pattern with the appropriate box. This is observed after daily alprazolam at 0.5 mg for two weeks.

The other behavioral test that was performed by this group was the Delayed Matching to Sample task. In this test, a complex visual stimulus is presented to the subject. After a delay of 0, 4, or 12 seconds, the subject is shown four visual stimuli, of which one of them matches the one they recently saw. After exposure to Xanax, the subjects performed worse and scored fewer accurate answers.

After long term use of Xanax, there may be symptoms that develop that are indicative of withdrawal. A person who stops using the drug may develop anxiety, difficulty sleeping, or seizures. When taken under the care of a medical professional, they will often slowly decrease the dosage of Xanax that the patient receives in order to minimize the risk of a sudden and possibly lethal withdrawal syndrome. As with most withdrawal symptoms, the symptoms that may appear are often the opposite of the intended function of the drug.