Psychology Wiki

Assessment | Biopsychology | Comparative | Cognitive | Developmental | Language | Individual differences | Personality | Philosophy | Social |
Methods | Statistics | Clinical | Educational | Industrial | Professional items | World psychology |

Biological: Behavioural genetics · Evolutionary psychology · Neuroanatomy · Neurochemistry · Neuroendocrinology · Neuroscience · Psychoneuroimmunology · Physiological Psychology · Psychopharmacology (Index, Outline)

Alprazolam chemical structure

IUPAC name
CAS number
ATC code


Chemical formula {{{chemical_formula}}}
Molecular weight 308.765
Bioavailability 80-90%
Metabolism Hepatic
Elimination half-life 6-12 hours
Excretion Renal
Pregnancy category {{{pregnancy_category}}}
Legal status {{{legal_status}}}
Routes of administration Oral

Alprazolam, also known under the trade-names Xanax and Niravam, is a short-acting drug in the benzodiazepine class used to treat severe anxiety disorders and as an adjunctive treatment for anxiety associated with depression.

Alprazolam was first synthesized by Upjohn (now a part of Pfizer) and is marketed under various trade names. Its patent (#3,987,052)[1] was filed on October 29, 1969, granted on October 19, 1976 and expired in September 1993.


Alprazolam is a triazolobenzodiazepine[2], that is, a benzodiazepine with a triazolo-ring attached to its structure. Benzodiazepines produce a variety of effects by modulating the GABAA subtype of the GABA receptor, the most prolific inhibitory receptor within the brain. The GABAA receptor is made up from 5 subunits out of a possible 19, and GABAA receptors made up of different combinations of subunits have different properties, different locations within the brain and importantly, different activities in regards to benzodiazepines.

In order for GABAA receptors to be sensitive to the action of benzodiazepines they need to contain an α and a γ subunit, where the benzodiazepine binds. Once bound, the benzodiazepine locks the GABAA receptor into a conformation where the neurotransmitter GABA has much higher affinity for the GABAA receptor, increasing the frequency of opening of the associated Chloride ion channel and hyperpolarising the membrane. This potentiates the inhibitory effect of the available GABA leading to sedatory and anxiolytic effects. As mentioned, different benzodiazepines can have different affinities for GABAA receptors made up of different collection of subunits. For instance, benzodiazepines with high activity at the α1 are associated with sedation whereas those with higher affinity for GABAA receptors containing α2 and/or α3 subunits have greater anxiolytic activity.

The binding site for benzodiazepines is distinct from the binding site for barbiturates and GABA on the GABA receptor.

There is some evidence for antidepressant treatment of major depression in out patient settings, evidence for inpatients is lacking;[3] other benzodiazepines are not known to have antidepressant activity.


Alprazolam is readily absorbed from the gastrointestinal tract. The peak plasma concentration is achieved in 1-2 hours. Most of the drug is bound to plasma protein, mainly serum albumin. Alprazolam is hydroxylated in the liver to α-hydroxyalprazolam, which is also pharmacologically active. This and other metabolites are later excreted in urine as glucuronides. Some of the drug is also excreted in unchanged form.


The main medical uses for alprazolam include:

  • Alprazolam is FDA licensed for the short term treatment (up to 8 weeks) of panic disorder, with or without agoraphobia. Alprazolam is very effective in preventing moderate to severe anxiety, essential tremor, panic attacks and other types of convulsive behaviors. Physicians who elect to prescribe alprazolam for longer than 8 weeks should be aware that continued efficacy has not been systematically demonstrated beyond 8 weeks use as tolerance to alprazolam's effects may occur after 8 weeks
  • Alprazolam is recommended for the short term treatment (2 - 4 weeks) of severe acute anxiety. Alprazolam should not generally be used for longer periods because the body becomes rapidly tolerant to the drugs effects with the risk of withdrawal symptoms when discontinuing the drug


Holographic advertisement for Xanax, 1989.

Xanax is the main and most commonly known brand name for alprazolam. There is a large variety of generic brand names for Alprazolam in use throughout the world. In English speaking countries alprazolam is sold under the following brand names: Alprax, Alprox, Alzam, Anxirid, Apo-Alpraz, Azor, Calmax, Gerax, Kalma, Novo-Alprazol, Nu-Alpraz, Xanax, Xanor, Zopax.[4]


Alprazolam is generally sold in generic form in the United States. It is also sold under many other brand names, depending on the country:

  • Xanax® - United States, Australia, United Kingdom, Turkey, Portugal, Ireland, Greece
  • Xanax XR® - (an extended release formulation) United States
  • Niravam® - (formulary that dissolves on the tongue) United States
  • Apo-Alpraz® - Canada (also made by other companies under different names)
  • Xanor® - Finland, Philippines, South Africa, Sweden, Norway
  • Kalma® - Australia, New Zealand
  • Ralozam® - Australia, New Zealand
  • Zamhexal® - Australia
  • Alplax® - Argentina
  • Alviz® - Indonesia
  • Alzolam® - India, Malaysia
  • Alprax® - India
  • Tranax® - India
  • Restyl® - Bahrain, Cyprus, Egypt, Iran, Iraq, Jordan, Kuwait, Lebanon, Libya, Oman, Qatar, Republic of Yemen, Saudi Arabia, Syria, United Arab Emirates
  • Tranquinal® - Ecuador, Peru
  • Trankimazin® - Spain
  • Tafil® - Costa Rica, Denmark, El Salvador, Germany, Guatemala, Honduras, Mexico, Nicaragua, Panama, Venezuela
  • Tafil AP® - (an extended release formulation) Mexico
  • Constan® - Japan
  • Solanax® - Japan
  • Zolarem® - Bahrain, Benin, Burkina-Faso, Cyprus, Egypt, Ethiopia, Gambia, Ghana, Guinea, Iran, Iraq, Israel, Ivory Coast, Jordan, Kenya, Kuwait, Lebanon, Liberia, Libya, Malawi, Mali, Mauritania, Mauritius, Morocco, Niger, Nigeria, Oman, Qatar, Republic of Yemen, Saudi Arabia, Senegal, Seychelles, Sierra-Leone, South Africa, Sudan, Syria, Tanzania, Tunia, Uganda, United Arab Emirates, Zambia, Zimbabwe
  • Zoldac® - Benin, Burkina-Faso, Ethiopia, Gambia, Ghana, Guinea, India, Ivory Coast, Kenya, Liberia, Malawi, Mali, Mauritania, Mauritius, Morocco, Niger, Nigeria, Senegal, Seychelles, Sierra-Leone, South Africa, Sudan, Tanzania, Tunia, Uganda, Zambia, Zimbabwe
  • Calmax® - Ireland

Side effects

Side effects of alprazolam may occur in patients and are more likely the higher the dosage taken. If signs of an allergic reaction occur such as hives, difficulty breathing, swelling of face, lips, tongue or throat occur medical attention should be sought immediately. Medical attention should also be sought immediately if signs of jaundice appear such as yellowing of the skin or eyes. Other side effects which may occur are as follows: [5][6][7]

Side effects other than those listed here may also occur. Talk to your doctor about any side effect that seems unusual or that is especially troublesome.

Physical dependence and withdrawal There is now a general consensus among psychiatrists that alprazolam and other benzodiazepines can cause withdrawal symptoms after long-term treatment and should be done slowly over a period of months (or even up to a year) to avoid serious withdrawal symptoms such as agitation, panic attacks, rebound anxiety, muscle cramps and seizures.[8] Some patients may benefit from a substitution with diazepam or clonazepam as these drugs remain in the bloodstream longer and therefore have less potential for abuse and dependence.

Patients taking a dosing regimen larger than 4 mg per day have an increased potential for dependence. This medication may cause withdrawal symptoms, which in some cases have been known to cause seizures. The discontinuation of this medication may also cause a reaction called rebound anxiety. Other withdrawal effects reported from discontinuing alprazolam therapy include homicidal ideation, rage reactions, hyperalertness, increased nightmares, and intrusive thoughts.[9]

When a patient discontinues use, they may experience the symptoms they had before taking medication. Symptoms may also be accompanied by other reactions including changes in mood, anxiety or sleep. Rebound anxiety is usually a result of abrupt discontinuation of this medication; patients who taper off are less likely to experience these symptoms.

Physical dependence is the major limiting factor against long term use of alprazolam and other benzodiazepines.

Factors which determine the severity of the benzodiazepine withdrawal syndrome experienced during dose reduction of alprazolam include:[10]

  • dosage
  • length of use
  • frequency of dosing
  • method of withdrawal[11]
  • personality characteristics of the individual
  • previous use of cross dependent/cross tolerant drugs (alcohol or other sedative hypnotic drugs)
  • current use of cross dependent/cross tolerant drugs (alcohol or other sedative hypnotic drugs)
  • Use of short acting high potency benzodiazepines for example alprazolam or lorazepam

Alprazolam has an exceptional history insofar soon after its introduction a large number of case reports were published in the medical literature of severe withdrawal symptoms related case reports of withdrawal psychoses, seizures and intense rebound anxiety upon discontinuation of alprazolam. In the United States a survey of physicians showed that 84% of physicians reported alprazolam as being extremely problematic in terms of the severity and prolonged nature of the benzodiazepine withdrawal syndrome after discontinuation. The benzodiazepines diazepam (Valium) and oxazepam were found to produce less severe withdrawal symptoms than alprazolam (Xanax) or lorazepam (Ativan).[10]

Alprazolam should never be abruptly discontinuated if take regularly for any length of time as severe withdrawal symptoms may occur. Severe psychosis has been reported in the medical literature from abrupt alprazolam withdrawal and death occurred from withdrawal related seizures after gradual dose reduction, which suggests that alprazolam when being discontinued should be done so very slowly over a prolonged period of time to avoid severe withdrawal symptoms.[12]


Use of alprazolam should be avoided in individuals with the following conditions:[13][14]


Women who are pregnant or are planning on becoming pregnant should avoid alprazolam.[16]


Teratogenic effects: Pregnancy Category D.

Nonteratogenic Effects

Nonteratogenic Effects: It should be considered that the child born of a mother who is receiving benzodiazepines may be at risk of developing withdrawal symptoms from the drug during the postnatal period. Also, neonatal flaccidity and respiratory problems have been reported in children born of mothers who have been receiving benzodiazepines.[17]

Labor and Delivery

Alprazolam has no established use in labor or delivery.

Nursing Mothers/Neonatal

Benzodiazepines, including alprazolam are known to be excreted in human milk.[18] Chronic administration of diazepam to nursing mothers has been reported to cause their infants to become lethargic and to lose weight. As a general rule, nursing should not be undertaken by mothers who use alprazolam.

Children of mothers who are taking alprazolam are considered at risk for withdrawal symptoms during the postnatal period. Some children born under these conditions have been reported to have neonatal flaccidity and respiratory problems. Likewise, nursing mothers should avoid alprazolam due to the fact that benzodiazepines are known to be passed into breast milk. This can cause infants to become lethargic and lose weight.[19]

Geriatric use

Elderly individuals should be cautious in the use of alprazolam due to the possibility of increased sensitivity to side effects, especially loss of coordination and drowsiness.[9]

Food and drug interactions

Eating grapefruits or drinking grapefruit juice while using alprazolam increases blood concentrations by inhibiting the intestinal metabolism.[20]

In fact, any drug that inhibits CYP3A4, for which alprazolam is a substrate, will increase serum concentrations of alprazolam significantly if administered prior or concurrently. Tagamet (cimetidine) is a widely used H2 blocker antacid that inhibits numerous cytochrome P450 enzymes.

Recreational use

alprazolam 2mg tablets

Alprazolam, like all benzodiazepines, has the potential for abuse. Although it is not manufactured illegally, it is often diverted to the black market. The state of relaxation, anxiolysis, and disinhibition induced by benzodiazepines is the main reason for their illicit use.

Improper injection of alprazolam is considered especially dangerous by medical professionals[21] due to the fact that, when crushed in water it will not fully dissolve (40µg/ml of H2O at pH 7, and 12 mg/mL at pH 1.2 per 1mg of alprazolam,[22]) potentially causing severe damage to arteries if not filtered properly. While it is somewhat soluble in alcohol, the combination of the two, particularly when injected, has the potential to cause a serious, and potentially fatal overdose. Alprazolam may also be insufflated; clinical testing dispels the rumor about less activity via insufflation.

Alprazolam is sometimes used with other recreational drugs to relieve the panic or distress of dysphoric reactions to psychedelics such as LSD and also to promote sleep in the "come-down" period following use of recreational drugs with stimulant or insomniac properties (such as LSD, cocaine, amphetamines, DXM, and MDMA along with the related amphetamines). It is also often used in conjunction with marijuana or heroin to potentiate the relaxing effect.

Patients at a High Risk for Abuse and Dependence

At a particularly high risk for misuse, abuse, and dependence are:

  • Patients with a history of alcohol or drug abuse and/or dependence
  • Emotionally unstable patients
  • Patients with severe personality disorders
  • Patients with chronic pain or other physical disorders

Patients from the aforementioned group should be monitored very closely during therapy for signs of abuse and development of dependence. Discontinue therapy if any of these signs are noted. Long-term therapy in these patients is not recommended.

Legal status

In the United States, alprazolam is a prescription drug and is assigned to Schedule IV of the Controlled Substances Act by the Drug Enforcement Administration. Under the UK drug misuse classification system benzodiazepines are class C drugs.[23] Internationally, alprazolam is included under the United Nations Convention on Psychotropic Substances as Schedule IV.[24]

See also


  1. Patent 3,987,052
  2. J Med. Chem. Vol. 14, p. 1078-1081 (1971) DOI: 10.1021/jm00293a015
  3. [1]
  4. [2]
  5. ALPRAZOLAM - ORAL (Xanax) side effects, medical uses, and drug interactions..
  6. Alprazolam – Complete medical information regarding this treatment of anxiety disorders on
  7. alprazolam Side Effects, Interactions and Information -
  8. Xanax side effects, medical uses, and withdrawal..
  9. Risse SC, Whitters A, Burke J, Chen S, Scurfield RM, Raskind MA. (1990). Severe withdrawal symptoms after discontinuation of alprazolam in eight patients with combat-induced posttraumatic stress disorder.. The Journal of clinical psychiatry. 51 (5): 206-9.
  10. 10.0 10.1 Wolf B, Griffiths RR. (1991). Physical dependence on benzodiazepines: differences within the class.. Drug and alcohol dependence. 29 (2): 153-6.
  11. [3]
  12. Haque W, Watson DJ, Bryant SG. (Jan 1990). Death following suspected alprazolam withdrawal seizures: a case report.. Texas medicine. 86 (1): 44-7.
  13. (2007). Alprazolam. British National Formulary.
  14. (2007). Alprazolam.
  15. Hori A. (Feb 1998). Pharmacotherapy for personality disorders.. Psychiatry and clinical neurosciences. 52 (1): 13-9.
  16. [4]
  17. García-Algar O, López-Vílchez MA, Martín I, Mur A, Pellegrini M, Pacifici R, Rossi S, Pichini S. (2007). Confirmation of gestational exposure to alprazolam by analysis of biological matrices in a newborn with neonatal sepsis.. Clinical toxicology (Philadelphia, Pa.). 45 (3): 295-8.
  18. Oo CY, Kuhn RJ, Desai N, Wright CE, McNamara PJ. (Sep 1995). Pharmacokinetics in lactating women: prediction of alprazolam transfer into milk.. British journal of clinical pharmacology. 40 (3): 231-6.
  19. [5][6]
  21. Eric C, Wang, Felix S, Chew. (2006). MR Findings of Alprazolam Injection into the Femoral Artery with Microembolization and Rhabdomyolysis. Radiology Case Reports 1 (3).
  22. [7]
  23. [8]
  24. List of psychotropic substances under international control

External links

This page uses Creative Commons Licensed content from Wikipedia (view authors).