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Systematic (IUPAC) name
CAS number 28981-97-7
ATC code N05BA12
PubChem 2118
DrugBank APRD00280
Chemical data
Formula C17H13ClN4 
Mol. mass 308.765
Pharmacokinetic data
Bioavailability 80-90%
Metabolism Hepatic
Half life 6-12 hours
Excretion Renal
Therapeutic considerations
Pregnancy cat.


Legal status

Schedule IV(US)

Routes 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 clinical depression.



"[The public often does] underestimate the extent to which certain disorders affect the general populace. When you treat them, it can make a tremendous amount of difference in their lives." (David Sheehan, first discovered alprazolam's efficacy in treating panic disorder.[1])

Alprazolam was first synthesized by Upjohn (now a part of Pfizer). Its patent (#3,987,052)[2] was filed on October 29, 1969, granted on October 19, 1976 and expired in September 1993. It was released in 1983 to international market and its use began around 1990 in Europe. The first indication for which alprazolam was approved was panic disorder. Upjohn took this direction at the behest of a young psychiatrist David Sheehan. Sheehan's suggestion was to use the confusion DSM-III created in the classification of anxiety disorders (a distinction had just been made in DSM-III between generalized anxiety disorder (GAD) and panic disorder). Panic disorder was, at that point, perceived to be rare and treatable only with tricyclic antidepressants; benzodiazepines were thought to be ineffective. However, from his clinical experience, Sheehan knew panic disorder to be both widespread among the populace and well responding to benzodiazepines. He suggested to Upjohn that marketing alprazolam for panic disorder will both cover new diagnostic territory and stress the unique potency of this drug. Sheehan describes that the first group of patients treated by alprazolam was so impressed by its action that they knew outright—this drug was going to be a hit. A few of them pooled their money and bought the Upjohn’s stock. Several months later, when alprazolam was approved by the FDA, they sold out and made a profit.[3]


Alprazolam is a triazolobenzodiazepine[4], 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 clinical depression in out patient settings, evidence for inpatients is lacking;[5] 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-approved 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 and necessitate discontinuation or physician-directed dose escalation.[6] However, long-term maintenance therapy on alprazolam is not unheard-of in the medical community, and, if a genuine therapeutic need exists, benefits must be weighed against risks.
  • Alprazolam is recommended for the short-term treatment (2-4 weeks) of severe acute anxiety. Alprazolam should only very rarely be used for longer periods of time -- the body becomes rapidly tolerant to the drug's effects, which may translate to decreased efficacy.[7][8] Decreased efficacy can lead to dose escalation, and the use of high doses puts the patient at higher risk for withdrawal if the drug is discontinued suddenly.



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, Helex, Kalma, Kinax, Neurol, Novo-Alprazol, Nu-Alpraz, Restyl, Xanax, Xanor, Zopax, Trika It is also commonly known as "Ladders" or "Bars" or "yellow buses" when laced, when sold or used illegally.[9]


  Imprints vary depending on drug manufacturer. The imprints above refer to the name-brand design in the United States and other first world countries,[10] however, every variety of alprazolam is generically available and thus individual pill design is left up to the manufacturer.

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:[11][12][13][14]

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 discontinuation should be done gradually 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.[citation needed] 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.[15]

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:[16]

  • dosage
  • length of use
  • frequency of dosing
  • method of withdrawal[17]
  • 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).[16]

Alprazolam should never be abruptly discontinued if taken regularly for any length of time because 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.[18]


Use of alprazolam should be avoided, or carefully monitored by medical professionals, in individuals with the following conditions:[19][20]


Overdoses can be mild to severe depending on how much of the drug is taken and if any other depressants have been taken. Xanax overdose reflect the central nervous system depresson of the brain and may include one or more of the following symptoms:

  • Somnolence (difficulty staying awake)
  • Mental confusion
  • Respiratory depression
  • Hypotension
  • Impaired motor functions
    • Impaired or absent reflexes
    • Impaired coordination
    • Impaired balance
    • Dizziness
  • Hypoventilation
  • Coma
  • Death

it is more likely that a person will die if alcohol is mixed with this drug, but still there has been cases of death with Aprozolam alone which have been fatal. Coma in severe cases especially with other central nervous system depressants may lead to death.


Women who are pregnant or are planning on becoming pregnant should avoid starting alprazolam.[22] If you are currently planning to become pregnant, discuss this and all medicines with your obstetrician or other doctor.

Teratogenicity classification

Marked Pregnancy Category D by the U.S. FDA.

Effects on the fetus

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.[23]

Labor and delivery

Alprazolam has no established use in labor or delivery.

Nursing mothers (neonates)

Benzodiazepines, including alprazolam are known to be excreted in human milk.[24] 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. Benzodiazepines are known to be passed into breast milk. This can cause infants to become lethargic and lose weight.[25]

Geriatric use

Elderly individuals should be cautious in the use of alprazolam due to the possibility of increased susceptibility to side effects, especially loss of coordination and drowsiness.[26]

Food and drug interactions

Eating grapefruits or drinking grapefruit juice while using alprazolam increases blood concentrations by inhibiting the intestinal metabolism.[27]

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.

Oral contraceptive pills, reduce the clearance of alprazolam which may lead to increased plasma levels of alprazolam and accumulation.[28]

Special precautions

Like all central nervous system depressants, including alcohol, alprazolam in doses of 0.5 mg and above can cause significant deterioration in alertness, combined with increased feelings of sleepiness.[29] People driving or conducting activities which require vigilance should exercise caution in using alprazolam or any other depressant.

Recreational use

  Alprazolam, like all benzodiazepines, has the potential for abuse. Although it is not manufactured illegally, and its misuse and abuse is dwarfed by benzodiazepines like flunitrazepam and temazepam, it is still often diverted to the black market, particularily in the United States where alprazolam is the most widely prescribed benzodiazepine. The state of relaxation, anxiolysis, and disinhibition induced by benzodiazepines is the main reason for their illicit use.

Most alprazolam abusers "are generally but not entirely limited to patients involved in a polydrug use pattern"[30] In fact, according to an April 2004 report by the U.S. SAMHSA, "over three-quarters (78%) of benzodiazepine-related (emergency room) visits involved 2 or more drugs."[31].

Injection of alprazolam is considered especially dangerous by medical professionals[32] because, 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[33]), 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 indicates potent activity through insufflation.[34]

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 polydrug abusers (someone who already uses at least one substance in a recreational context). However, the following can also indicate potential problems in the future:

  • Patients with a history of alcohol or drug abuse and/or dependence
  • Patients with severe personality disorders or emotional instability
  • 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 because it may cause addiction. Discontinue therapy if any of these signs are noted. Long-term therapy in these patients is not recommended, unless the net benefit to the patient outweighs the net risk.

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.[35] Internationally, alprazolam is included under the United Nations Convention on Psychotropic Substances as Schedule IV.[36]


  1. ^ [1]
  2. ^ Patent 3,987,052
  3. ^ Healy, David (2000). The Psychopharmacologists, Vol. III: Interviews. London: Arnold, 479-504. ISBN 0-340-761105. 
  4. ^ J Med. Chem. Vol. 14, p. 1078-1081 (1971) DOI: 10.1021/jm00293a015
  5. ^ [2]
  6. ^ FDA (23rd). FDA APPROVED LABELING FOR XANAX XR (pdf) 4. Federal Drug Administration. Retrieved on 2nd Aug 2007. “The longer-term efficacy of XANAX XR has not been systematically evaluated. Thus, the physician who elects to use this drug for periods longer than 8 weeks should periodically reassess the usefulness of the drug for the individual patient.”
  7. ^ NetDoctor (1). Xanax. Retrieved on 2nd Aug 2007.
  8. ^ The British National Formulary (2007). Alprazolam. BNF. Retrieved on 2nd Aug 2007.
  9. ^ [3]
  10. ^ [4]
  11. ^ Complete Alprazolam information from Retrieved on 2nd Aug 2007.
  12. ^ ALPRAZOLAM - ORAL (Xanax) side effects, medical uses, and drug interactions.. Retrieved on 2nd Aug 2007.
  13. ^ Alprazolam – Complete medical information regarding this treatment of anxiety disorders on Retrieved on 2nd Aug 2007.
  14. ^ alprazolam Side Effects, Interactions and Information - Retrieved on 2nd Aug 2007.
  15. ^ 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. PMID 2335496.
  16. ^ a b Wolf B; Griffiths RR. (1991). "Physical dependence on benzodiazepines: differences within the class.". Drug and alcohol dependence. 29 (2): 153-6. PMID 1686752.
  17. ^ The Ashton Manual - Benzodiazepines: How They Work and How to Withdraw by professor Heather Ashton
  18. ^ Haque W; Watson DJ, Bryant SG. (Jan 1990). "Death following suspected alprazolam withdrawal seizures: a case report.". Texas medicine. 86 (1): 44-7. PMID 2300914.
  19. ^ Alprazolam. British National Formulary (2007). Retrieved on 3rd Aug 2007.
  20. ^ (2007). Alprazolam. Retrieved on 3rd Aug 2007.
  21. ^ Hori A. (Feb 1998). "Pharmacotherapy for personality disorders.". Psychiatry and clinical neurosciences. 52 (1): 13-9. PMID 9682928.
  22. ^ [5]
  23. ^ 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. PMID 17453885.
  24. ^ 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. PMID 8527284.
  25. ^ [6][7]
  26. ^]
  27. ^
  28. ^ Back DJ; Orme ML. (Jun 1990). "Pharmacokinetic drug interactions with oral contraceptives.". Clin Pharmacokinet. 18 (6): 472-84. PMID 2191822.
  29. ^ Kozená L; Frantik E, Horváth M. (May 1995). "Vigilance impairment after a single dose of benzodiazepines.". Psychopharmacology (Berl). 119 (1): 39-45. PMID 7675948.
  30. ^ Landry, J. Understanding Drugs of Abuse: The Processes of Addiction, 1994.
  31. ^
  32. ^ Eric C; Wang, Felix S, Chew. (2006). "MR Findings of Alprazolam Injection into the Femoral Artery with Microembolization and Rhabdomyolysis" (pdf). Radiology Case Reports 1 (3).
  33. ^ [8]
  34. ^
  35. ^ [9]
  36. ^ List of psychotropic substances under international control
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Alprazolam". A list of authors is available in Wikipedia.
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