Oxazepam

Last updated
Oxazepam
Oxazepam.svg
Oxazepam3d.png
Clinical data
Pronunciation /ɒkˈsæzɪpæm/
ok-SAZ-i-pam
Trade names Serax, Alepam, Serepax, others
Addiction
liability 		Low–moderate
Routes of
administration 		By mouth
Drug class Benzodiazepine
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability 92.8%
Metabolism Hepatic (glucuronidation)
Onset of action 30 - 120 minutes
Elimination half-life 6–9 hours [3] [4] [5]
Duration of action 6 - 12 hours
Excretion Renal
Identifiers
  • (RS)-7-Chloro-3-hydroxy-5-phenyl-1,3-dihydro-1,4-benzodiazepin-2-one [6]
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.009.161 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C15H11ClN2O2
Molar mass 286.71 g·mol−1
3D model (JSmol)
Melting point 205 to 206 °C (401 to 403 °F)
  • O=C1Nc2ccc(Cl)cc2C(c2ccccc2)=NC1O
  • InChI=1S/C15H11ClN2O2/c16-10-6-7-12-11(8-10)13(9-4-2-1-3-5-9)18-15(20)14(19)17-12/h1-8,15,18,20H X mark.svgN
  • Key:IMAUTQQURLXUGJ-UHFFFAOYSA-N X mark.svgN
   (verify)

Oxazepam is a short-to-intermediate-acting benzodiazepine. [7] [8] Oxazepam is used for the treatment of anxiety, [9] [10] insomnia, and to control symptoms of alcohol withdrawal syndrome.

Contents

It is a metabolite of diazepam, prazepam, and temazepam, [11] and has moderate amnesic, anxiolytic, anticonvulsant, hypnotic, sedative, and skeletal muscle relaxant properties compared to other benzodiazepines. [12]

It was patented in 1962 and approved for medical use in 1964. [13]

Medical uses

It is an intermediate-acting benzodiazepine with a slow onset of action, [14] so it is usually prescribed to individuals who have trouble staying asleep, rather than falling asleep. It is commonly prescribed for anxiety disorders with associated tension, irritability, and agitation. It is also prescribed for drug and alcohol withdrawal, and for anxiety associated with depression. Oxazepam is sometimes prescribed off-label to treat social phobia, post-traumatic stress disorder, insomnia, premenstrual syndrome, and other conditions. [15]

Oxazepam DOJ.jpg

Side effects

The side effects of oxazepam are similar to those of other benzodiazepines, and may include dizziness, drowsiness, headache, memory impairment, paradoxical excitement, and anterograde amnesia, but does not affect transient global amnesia.[ citation needed ] Withdrawal effects due to rapid decreases in dosage or abrupt discontinuation of oxazepam may include abdominal and muscle cramps, seizures, depression, insomnia, sweating, tremors, or nausea and vomiting. [16]

In September 2020, the U.S. Food and Drug Administration (FDA) required the boxed warning be updated for all benzodiazepine medicines to describe the risks of abuse, misuse, addiction, physical dependence, and withdrawal reactions consistently across all the medicines in the class. [17]

Tolerance, dependence and withdrawal

Oxazepam, as with other benzodiazepine drugs, can cause tolerance, physical dependence, addiction, and benzodiazepine withdrawal syndrome. Withdrawal from oxazepam or other benzodiazepines often leads to withdrawal symptoms which are similar to those seen during alcohol and barbiturate withdrawal. The higher the dose and the longer the drug is taken, the greater the risk of experiencing unpleasant withdrawal symptoms. Withdrawal symptoms can occur, though, at standard dosages and also after short-term use. Benzodiazepine treatment should be discontinued as soon as possible by a slow and gradual dose reduction regimen. [18]

Contraindications

Oxazepam is contraindicated in myasthenia gravis, chronic obstructive pulmonary disease, and limited pulmonary reserve, as well as severe hepatic disease.

Special precautions

Benzodiazepines require special precautions if used in the elderly, during pregnancy, in children, alcohol- or drug-dependent individuals, and individuals with comorbid psychiatric disorders. [19] Benzodiazepines including oxazepam are lipophilic drugs and rapidly penetrate membranes, so rapidly crosses over into the placenta with significant uptake of the drug. Use of benzodiazepines in late pregnancy, especially high doses, may result in floppy infant syndrome. [20]

Pregnancy

Oxazepam, when taken during the third trimester, causes a definite risk to the neonate, including a severe benzodiazepine withdrawal syndrome including hypotonia, reluctance to suck, apnoeic spells, cyanosis, and impaired metabolic responses to cold stress. Floppy infant syndrome and sedation in the newborn may also occur. Symptoms of floppy infant syndrome and the neonatal benzodiazepine withdrawal syndrome have been reported to persist from hours to months after birth. [21]

Interactions

As oxazepam is an active metabolite of diazepam, an overlap in possible interactions is likely with other drugs or food, with exception of the pharmacokinetic CYP450 interactions (e.g. with cimetidine). Precautions and following the prescription are required when taking oxazepam (or other benzodiazepines) in combinations with antidepressants or opioids. Concurrent use of these medications can interact in a way that is difficult to predict. Drinking alcohol when taking oxazepam is not recommended. Concomitant use of oxazepam and alcohol can lead to increased sedation, memory impairment, ataxia, decreased muscle tone, and, in severe cases or in predisposed patients, respiratory depression and coma.

Overdose

Oxazepam is generally less toxic in overdose than other benzodiazepines. [22] Important factors which affect the severity of a benzodiazepine overdose include the dose ingested, the age of the patient, and health status prior to overdose. Benzodiazepine overdoses can be much more dangerous if a coingestion of other CNS depressants such as opiates or alcohol has occurred. Symptoms of an oxazepam overdose include: [23] [24] [25]

Pharmacology

Oxazepam is an intermediate-acting benzodiazepine of the 3-hydroxy family; it acts on benzodiazepine receptors, resulting in increased effect of GABA to the GABAA receptor which results in inhibitory effects on the central nervous system. [26] [27] The half-life of oxazepam is between 6 and 9 hours. [5] [4] [28] It has been shown to suppress cortisol levels. [29] Oxazepam is the most slowly absorbed and has the slowest onset of action of all the common benzodiazepines according to one British study. [30]

Oxazepam is an active metabolite formed during the breakdown of diazepam, nordazepam, and certain similar drugs. It may be safer than many other benzodiazepines in patients with impaired liver function because it does not require hepatic oxidation, but rather, it is simply metabolized by glucuronidation, so oxazepam is less likely to accumulate and cause adverse reactions in the elderly or people with liver disease. Oxazepam is similar to lorazepam in this respect. [31] Preferential storage of oxazepam occurs in some organs, including the heart of the neonate. Absorption by any administered route and the risk of accumulation is significantly increased in the neonate, and withdrawal of oxazepam during pregnancy and breast feeding is recommended, as oxazepam is excreted in breast milk. [32]

2 mg of oxazepam equates to 1 mg of diazepam according to the benzodiazepine equivalency converter, therefore 20 mg of oxazepam according to BZD equivalency equates to 10 mg of diazepam and 15 mg oxazepam to 7.5 mg diazepam (rounded up to 8 mg of diazepam). [33] Some BZD equivalency converters use 3 to 1 (oxazepam to diazepam), 1 to 3 (diazepam to oxazepam) as the ratio (3:1 and 1:3), so 15 mg of oxazepam would equate to 5 mg of diazepam. [34]

Chemistry

Oxazepam exists as a racemic mixture. [35] Early attempts to isolate enantiomers were unsuccessful; the corresponding acetate has been isolated as a single enantiomer. Given the different rates of epimerization that occur at different pH levels, it was determined that there would be no therapeutic benefit to the administration of a single enantiomer over the racemic mixture. [36]

Frequency of use

Oxazepam, along with diazepam, nitrazepam, and temazepam, were the four benzodiazepines listed on the pharmaceutical benefits scheme and represented 82% of the benzodiazepine prescriptions in Australia in 1990–1991. [37] It is in several countries the benzodiazepine of choice for novice users, due to a low chance of accumulation and a relatively slow absorption speed. [38]

Society and culture

Misuse

Oxazepam has the potential for misuse, defined as taking the drug to achieve a high, or continuing to take the drug in the long term against medical advice. [39] Benzodiazepines, including diazepam, oxazepam, nitrazepam, and flunitrazepam, accounted for the largest volume of forged drug prescriptions in Sweden from 1982 to 1986. During this time, a total of 52% of drug forgeries were for benzodiazepines, suggesting they were a major prescription drug class of abuse. [40]

However, due to its slow rate of absorption and its slow onset of action, [30] oxazepam has a relatively low potential for abuse compared to some other benzodiazepines, such as temazepam, flunitrazepam, or triazolam. This is similar to the varied potential for abuse between different drugs of the barbiturate class. [41]

Oxazepam is a Schedule IV drug under the Convention on Psychotropic Substances. [42]

Brand names

It is marketed under many brand names worldwide, including: Alepam, Alepan, Anoxa, Anxiolit, Comedormir, durazepam, Murelax, Nozepam, Oksazepam, Opamox, Ox-Pam, Oxa-CT, Oxabenz, Oxamin, Oxapam, Oxapax, Oxascand, Oxaze, Oxazepam, Oxazépam, Oxazin, Oxepam, Praxiten, Purata, Selars, Serax, Serepax, Seresta, Séresta, Serpax, Sobril, Tazepam, Vaben, and Youfei. [43]

It is also marketed in combination with hyoscine as Novalona and in combination with alanine as Pausafrent T. [43]

Environmental concerns

In 2013, a laboratory study which exposed European perch to oxazepam concentrations equivalent to those present in European rivers (1.8 μg/L) found that they exhibited increased activity, reduced sociality, and higher feeding rate. [44] In 2016, a follow-up study which exposed salmon smolt to oxazepam for seven days before letting them migrate observed increased intensity of migratory behaviour compared to controls. [45] A 2019 study associated this faster, bolder behaviour in exposed smolt to increased mortality due to a higher likelihood of being predated on. [46]

On the other hand, a 2018 study from the same authors, which kept 480 European perch and 12 northern pikes in 12 ponds over 70 days, half of them control and half spiked with oxazepam, found no significant difference in either perch growth or mortality. However, it suggested that the latter could be explained by the exposed perch and pike being equally hampered by oxazepam, rather than the lack of an overall effect. [47] Lastly, a 2021 study built on these results by comparing two whole lakes filled with perch and pikes - one control while the other was exposed to oxazepam 11 days into experiment, at concentrations between 11 and 24 μg/L, which is 200 times greater than the reported concentrations in the European rivers. Even so, there were no measurable effects on pike behaviour after the addition of oxazepam, while the effects on perch behaviour were found to be negligible. The authors concluded that the effects previously attributed to oxazepam were instead likely caused by a combination of fish being stressed by human handling and small aquaria, followed by being exposed to a novel environment. [48]

Related Research Articles

<span class="mw-page-title-main">Benzodiazepine</span> Class of depressant drugs

Benzodiazepines, colloquially known as "benzos", are a class of depressant drugs whose core chemical structure is the fusion of a benzene ring and a diazepine ring. They are prescribed to treat conditions such as anxiety disorders, insomnia, and seizures. The first benzodiazepine, chlordiazepoxide (Librium), was discovered accidentally by Leo Sternbach in 1955, and was made available in 1960 by Hoffmann–La Roche, which followed with the development of diazepam (Valium) three years later, in 1963. By 1977, benzodiazepines were the most prescribed medications globally; the introduction of selective serotonin reuptake inhibitors (SSRIs), among other factors, decreased rates of prescription, but they remain frequently used worldwide.

<span class="mw-page-title-main">Diazepam</span> Benzodiazepine sedative

Diazepam, sold under the brand name Valium among others, is a medicine of the benzodiazepine family that acts as an anxiolytic. It is used to treat a range of conditions, including anxiety, seizures, alcohol withdrawal syndrome, muscle spasms, insomnia, and restless legs syndrome. It may also be used to cause memory loss during certain medical procedures. It can be taken orally, as a suppository inserted into the rectum, intramuscularly, intravenously or used as a nasal spray. When injected intravenously, effects begin in one to five minutes and last up to an hour. When taken by mouth, effects begin after 15 to 60 minutes.

<span class="mw-page-title-main">Temazepam</span> Insomnia medication

Temazepam, sold under the brand name Restoril among others, is a medication of the benzodiazepine class which is generally used to treat severe or debilitating insomnia. It is taken by mouth. Temazepam is rapidly absorbed, and significant hypnotic effects begin in less than 30 minutes and can last for up to eight hours. Prescriptions for hypnotics such as temazepam have seen a dramatic decrease since 2010, while anxiolytics such as alprazolam, clonazepam, and lorazepam have increased or remained stable. Temazepam and similar hypnotics, such as triazolam (Halcion) are generally reserved for severe and debilitating insomnia. They have largely been replaced by z-drugs and atypical antidepressants as first line treatment for insomnia.

<span class="mw-page-title-main">Alprazolam</span> Benzodiazepine medication

Alprazolam, sold under the brand name Xanax among others, is a fast-acting, potent tranquilizer of moderate duration within the triazolobenzodiazepine group of chemicals called benzodiazepines. Alprazolam is most commonly prescribed in the management of anxiety disorders, especially panic disorder and generalized anxiety disorder (GAD). Other uses include the treatment of chemotherapy-induced nausea, together with other treatments. GAD improvement occurs generally within a week. Alprazolam is generally taken orally.

<span class="mw-page-title-main">Lorazepam</span> Benzodiazepine medication

Lorazepam, sold under the brand name Ativan among others, is a benzodiazepine medication. It is used to treat anxiety, trouble sleeping, severe agitation, active seizures including status epilepticus, alcohol withdrawal, and chemotherapy-induced nausea and vomiting. It is also used during surgery to interfere with memory formation and to sedate those who are being mechanically ventilated. It is also used, along with other treatments, for acute coronary syndrome due to cocaine use. It can be given orally, transdermally, intravenously (IV), or intramuscularly When given by injection, onset of effects is between one and thirty minutes and effects last for up to a day.

<span class="mw-page-title-main">Clonazepam</span> Benzodiazepine medication

Clonazepam, sold under the brand name Klonopin among others, is a benzodiazepine medication used to prevent and treat anxiety disorders, seizures, bipolar mania, agitation associated with psychosis, obsessive–compulsive disorder (OCD), and akathisia. It is a long-acting tranquilizer of the benzodiazepine class. It possesses anxiolytic, anticonvulsant, sedative, hypnotic, and skeletal muscle relaxant properties. It is typically taken orally but is also used intravenously. Effects begin within one hour and last between eight and twelve hours in adults.

<span class="mw-page-title-main">Bromazepam</span> Benzodiazepine drug

Bromazepam, sold under many brand names, is a benzodiazepine. It is mainly an anti-anxiety agent with similar side effects to diazepam. In addition to being used to treat anxiety or panic states, bromazepam may be used as a premedicant prior to minor surgery. Bromazepam typically comes in doses of 3 mg and 6 mg tablets.

<span class="mw-page-title-main">Clobazam</span> Benzodiazepine class medication

Clobazam, sold under the brand names Frisium, Onfi and others, is a benzodiazepine class medication that was patented in 1968. Clobazam was first synthesized in 1966 and first published in 1969. Clobazam was originally marketed as an anxioselective anxiolytic since 1970, and an anticonvulsant since 1984. The primary drug-development goal was to provide greater anxiolytic, anti-obsessive efficacy with fewer benzodiazepine-related side effects.

<span class="mw-page-title-main">Nordazepam</span> Benzodiazepine derivative medication

Nordazepam is a 1,4-benzodiazepine derivative. Like other benzodiazepine derivatives, it has amnesic, anticonvulsant, anxiolytic, muscle relaxant, and sedative properties. However, it is used primarily in the treatment of anxiety disorders. It is an active metabolite of diazepam, chlordiazepoxide, clorazepate, prazepam, pinazepam, and medazepam.

<span class="mw-page-title-main">Clorazepate</span> Benzodiazepine medication

Clorazepate, sold under the brand name Tranxene among others, is a benzodiazepine medication. It possesses anxiolytic, anticonvulsant, sedative, hypnotic, and skeletal muscle relaxant properties. Clorazepate is an unusually long-lasting benzodiazepine and serves as a prodrug for the equally long-lasting desmethyldiazepam, which is rapidly produced as an active metabolite. Desmethyldiazepam is responsible for most of the therapeutic effects of clorazepate.

<span class="mw-page-title-main">Loprazolam</span> Benzodiazepine

Loprazolam (triazulenone) marketed under many brand names is a benzodiazepine medication. It possesses anxiolytic, anticonvulsant, hypnotic, sedative and skeletal muscle relaxant properties. It is licensed and marketed for the short-term treatment of moderately-severe insomnia.

<span class="mw-page-title-main">Prazepam</span> Benzodiazepine drug

Prazepam is a benzodiazepine derivative drug developed by Warner-Lambert in the 1960s. It possesses anxiolytic, anticonvulsant, sedative and skeletal muscle relaxant properties. Prazepam is a prodrug for desmethyldiazepam which is responsible for the therapeutic effects of prazepam.

<span class="mw-page-title-main">Tofisopam</span> Anxiolytic medication

Tofisopam is an anxiolytic that is marketed in several European countries. Chemically, it is a 2,3-benzodiazepine. Unlike other anxiolytic benzodiazepines however, tofisopam does not have anticonvulsant, sedative, skeletal muscle relaxant, motor skill-impairing or amnestic properties. While it may not be an anticonvulsant in and of itself, it has been shown to enhance the anticonvulsant action of classical 1,4-benzodiazepines and muscimol, but not sodium valproate, carbamazepine, phenobarbital, or phenytoin. Tofisopam is indicated for the treatment of anxiety and alcohol withdrawal, and is prescribed in a dosage of 50–300 mg per day divided into three doses. Peak plasma levels are attained two hours after an oral dose. Tofisopam is not reported as causing dependence to the same extent as other benzodiazepines, but is still recommended to be prescribed for a maximum of 12 weeks.

<span class="mw-page-title-main">Bretazenil</span> Chemical compound

Bretazenil (Ro16-6028) is an imidazopyrrolobenzodiazepine anxiolytic drug which is derived from the benzodiazepine family, and was invented in 1988. It is most closely related in structure to the GABA antagonist flumazenil, although its effects are somewhat different. It is classified as a high-potency benzodiazepine due to its high affinity binding to benzodiazepine binding sites where it acts as a partial agonist. Its profile as a partial agonist and preclinical trial data suggests that it may have a reduced adverse effect profile. In particular bretazenil has been proposed to cause a less strong development of tolerance and withdrawal syndrome. Bretazenil differs from traditional 1,4-benzodiazepines by being a partial agonist and because it binds to α1, α2, α3, α4, α5 and α6 subunit containing GABAA receptor benzodiazepine receptor complexes. 1,4-benzodiazepines bind only to α1, α2, α3 and α5GABAA benzodiazepine receptor complexes.

<span class="mw-page-title-main">Chlordiazepoxide</span> Benzodiazepine class sedative and hypnotic medication

Chlordiazepoxide, trade name Librium among others, is a sedative and hypnotic medication of the benzodiazepine class; it is used to treat anxiety, insomnia and symptoms of withdrawal from alcohol, benzodiazepines, and other drugs.

<span class="mw-page-title-main">Benzodiazepine withdrawal syndrome</span> Signs and symptoms due to benzodiazepine discontinuation in physically dependent persons

Benzodiazepine withdrawal syndrome is the cluster of signs and symptoms that may emerge when a person who has been taking benzodiazepines as prescribed develops a physical dependence on them and then reduces the dose or stops taking them without a safe taper schedule.

<span class="mw-page-title-main">Alcohol detoxification</span> Abrupt cessation of alcohol intake

Alcohol detoxification is the abrupt cessation of alcohol intake in individuals that have alcohol use disorder. This process is often coupled with substitution of drugs that have effects similar to the effects of alcohol in order to lessen the symptoms of alcohol withdrawal. When withdrawal does occur, it results in symptoms of varying severity.

<span class="mw-page-title-main">Benzodiazepine dependence</span> Medical condition

Benzodiazepine dependence defines a situation in which one has developed one or more of either tolerance, withdrawal symptoms, drug seeking behaviors, such as continued use despite harmful effects, and maladaptive pattern of substance use, according to the DSM-IV. In the case of benzodiazepine dependence, the continued use seems to be typically associated with the avoidance of unpleasant withdrawal reaction rather than with the pleasurable effects of the drug. Benzodiazepine dependence develops with long-term use, even at low therapeutic doses, often without the described drug seeking behavior and tolerance.

<span class="mw-page-title-main">Benzodiazepine overdose</span> Medical condition

Benzodiazepine overdose describes the ingestion of one of the drugs in the benzodiazepine class in quantities greater than are recommended or generally practiced. The most common symptoms of overdose include central nervous system (CNS) depression, impaired balance, ataxia, and slurred speech. Severe symptoms include coma and respiratory depression. Supportive care is the mainstay of treatment of benzodiazepine overdose. There is an antidote, flumazenil, but its use is controversial.

<span class="mw-page-title-main">Benzodiazepine use disorder</span> Illicit use of benzodiazepine drugs

Benzodiazepine use disorder (BUD), also called misuse or abuse, is the use of benzodiazepines without a prescription and/or for recreational purposes, which poses risks of dependence, withdrawal and other long-term effects. Benzodiazepines are one of the more common prescription drugs used recreationally. When used recreationally benzodiazepines are usually administered orally but sometimes they are taken intranasally or intravenously. Recreational use produces effects similar to alcohol intoxication.

References

  1. ↑ Anvisa (2023-03-31). "RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial" [Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control] (in Brazilian Portuguese). Diário Oficial da União (published 2023-04-04). Archived from the original on 2023-08-03. Retrieved 2023-08-16.
  2. ↑ "FDA-sourced list of all drugs with black box warnings (Use Download Full Results and View Query links.)". nctr-crs.fda.gov. FDA . Retrieved 22 Oct 2023.
  3. ↑ Encadré 1. Anxiolytiques à demi-vie courte (< 20 heures) et sans métabolite actif par ordre alphabétique de DCI
  4. 1 2 Sonne J, Loft S, Døssing M, Vollmer-Larsen A, Olesen KL, Victor M, et al. (1988). "Bioavailability and pharmacokinetics of oxazepam". European Journal of Clinical Pharmacology. 35 (4): 385–389. doi:10.1007/bf00561369. PMID   3197746. S2CID   31007311.
  5. 1 2 Sonne J, Boesgaard S, Poulsen HE, Loft S, Hansen JM, Døssing M, Andreasen F (November 1990). "Pharmacokinetics and pharmacodynamics of oxazepam and metabolism of paracetamol in severe hypothyroidism". British Journal of Clinical Pharmacology. 30 (5): 737–742. doi:10.1111/j.1365-2125.1990.tb03844.x. PMC   1368175 . PMID   2271373.
  6. ↑ CID 4616 from PubChem
  7. ↑ "Benzodiazepine Names". non-benzodiazepines.org.uk. Archived from the original on 2008-12-08. Retrieved 2008-12-29.
  8. ↑ "FASS". Läkemedelsindustriföreningens Service AB. Archived from the original on 2011-10-01. Retrieved 2011-02-03.
  9. ↑ Janecek J, Vestre ND, Schiele BC, Zimmermann R (December 1966). "Oxazepam in the treatment of anxiety states: a controlled study". Journal of Psychiatric Research. 4 (3): 199–206. doi:10.1016/0022-3956(66)90007-0. PMID   20034170.
  10. ↑ Sarris J, Scholey A, Schweitzer I, Bousman C, Laporte E, Ng C, et al. (May 2012). "The acute effects of kava and oxazepam on anxiety, mood, neurocognition; and genetic correlates: a randomized, placebo-controlled, double-blind study". Human Psychopharmacology. 27 (3): 262–269. doi:10.1002/hup.2216. PMID   22311378. S2CID   44801451.
  11. ↑ "Oxazepam (IARC Summary & Evaluation, Volume 66, 1996)". IARC. Archived from the original on 2008-09-07. Retrieved 2009-03-12.
  12. ↑ Mandrioli R, Mercolini L, Raggi MA (October 2008). "Benzodiazepine metabolism: an analytical perspective". Current Drug Metabolism. 9 (8): 827–844. doi:10.2174/138920008786049258. PMID   18855614. Archived from the original on 2009-03-17.
  13. ↑ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 536. ISBN   9783527607495.
  14. ↑ Galanter M, Kleber HD (1 July 2008). The American Psychiatric Publishing Textbook of Substance Abuse Treatment (4th ed.). United States of America: American Psychiatric Publishing Inc. p. 216. ISBN   978-1-58562-276-4.
  15. ↑ "Serax (oxazepam)" (PDF). Archived from the original (PDF) on 2011-07-15. Retrieved 2009-04-22.
  16. ↑ "Oxazepam Uses, Side Effects & Warnings - Drugs.com". drugs.com. Archived from the original on 2009-06-04.
  17. ↑ "FDA expands Boxed Warning to improve safe use of benzodiazepine drug". U.S. Food and Drug Administration (FDA). 23 September 2020. Retrieved 23 September 2020.PD-icon.svg This article incorporates text from this source, which is in the public domain .
  18. ↑ MacKinnon GL, Parker WA (1982). "Benzodiazepine withdrawal syndrome: a literature review and evaluation". The American Journal of Drug and Alcohol Abuse. 9 (1): 19–33. doi:10.3109/00952998209002608. PMID   6133446.
  19. ↑ Authier N, Balayssac D, Sautereau M, Zangarelli A, Courty P, Somogyi AA, et al. (November 2009). "Benzodiazepine dependence: focus on withdrawal syndrome". Annales Pharmaceutiques Françaises. 67 (6): 408–413. doi:10.1016/j.pharma.2009.07.001. PMID   19900604.
  20. ↑ Kanto JH (May 1982). "Use of benzodiazepines during pregnancy, labour and lactation, with particular reference to pharmacokinetic considerations". Drugs. 23 (5): 354–380. doi:10.2165/00003495-198223050-00002. PMID   6124415. S2CID   27014006.
  21. ↑ McElhatton PR (Nov–Dec 1994). "The effects of benzodiazepine use during pregnancy and lactation". Reproductive Toxicology. 8 (6): 461–475. Bibcode:1994RepTx...8..461M. doi:10.1016/0890-6238(94)90029-9. PMID   7881198.
  22. ↑ Buckley NA, Dawson AH, Whyte IM, O'Connell DL (January 1995). "Relative toxicity of benzodiazepines in overdose". BMJ. 310 (6974): 219–221. doi:10.1136/bmj.310.6974.219. PMC   2548618 . PMID   7866122.
  23. ↑ Gaudreault P, Guay J, Thivierge RL, Verdy I (1991). "Benzodiazepine poisoning. Clinical and pharmacological considerations and treatment". Drug Safety. 6 (4): 247–265. doi:10.2165/00002018-199106040-00003. PMID   1888441. S2CID   27619795.
  24. ↑ Perry HE, Shannon MW (June 1996). "Diagnosis and management of opioid- and benzodiazepine-induced comatose overdose in children". Current Opinion in Pediatrics. 8 (3): 243–247. doi:10.1097/00008480-199606000-00010. PMID   8814402. S2CID   43105029.
  25. ↑ Busto U, Kaplan HL, Sellers EM (February 1980). "Benzodiazepine-associated emergencies in Toronto". The American Journal of Psychiatry. 137 (2): 224–227. doi:10.1176/ajp.137.2.224. PMID   6101526.
  26. ↑ Skerritt JH, Johnston GA (May 1983). "Enhancement of GABA binding by benzodiazepines and related anxiolytics". European Journal of Pharmacology. 89 (3–4): 193–198. doi:10.1016/0014-2999(83)90494-6. PMID   6135616.
  27. ↑ Oelschläger H (July 1989). "[Chemical and pharmacologic aspects of benzodiazepines]". Schweizerische Rundschau für Medizin Praxis = Revue Suisse de Médecine Praxis. 78 (27–28): 766–772. PMID   2570451.
  28. ↑ https://www.has-sante.fr/upload/docs/application/pdf/2011-11/mama_troubles_comportement_encadre_1_anxiolitiques.pdf%5B%5D
  29. ↑ Christensen P, Lolk A, Gram LF, Kragh-Sørensen P (1992). "Benzodiazepine-induced sedation and cortisol suppression. A placebo-controlled comparison of oxazepam and nitrazepam in healthy male volunteers". Psychopharmacology. 106 (4): 511–516. doi:10.1007/BF02244823. PMID   1349754. S2CID   29331503.
  30. 1 2 Serfaty M, Masterton G (September 1993). "Fatal poisonings attributed to benzodiazepines in Britain during the 1980s". The British Journal of Psychiatry. 163 (3): 386–393. doi:10.1192/bjp.163.3.386. PMID   8104653. S2CID   46001278.
  31. ↑ Sabath LD (December 1975). "Current status of treatment of pneumonia". Southern Medical Journal. 68 (12): 1507–1511. doi:10.1097/00007611-197512000-00012. PMID   0792. S2CID   20789345.
  32. ↑ Olive G, Dreux C (January 1977). "[Pharmacologic bases of use of benzodiazepines in peréinatal medicine]". Archives Françaises de Pédiatrie. 34 (1): 74–89. PMID   851373.
  33. ↑ "benzo.org.uk : Benzodiazepine Equivalence Table".
  34. ↑ "Benzodiazepine equivalent dosage converter". GlobalRPH. Retrieved 2019-09-21.
  35. ↑ Aso Y, Yoshioka S, Shibazaki T, Uchiyama M (May 1988). "The kinetics of the racemization of oxazepam in aqueous solution". Chemical & Pharmaceutical Bulletin. 36 (5): 1834–1840. doi: 10.1248/cpb.36.1834 . PMID   3203421.
  36. ↑ Crossley RJ (1995). Chirality and Biological Activity of Drugs. CRC Press. ISBN   978-0849391408.
  37. ↑ Mant A, Whicker SD, McManus P, Birkett DJ, Edmonds D, Dumbrell D (December 1993). "Benzodiazepine utilisation in Australia: report from a new pharmacoepidemiological database". Australian Journal of Public Health. 17 (4): 345–349. doi: 10.1111/j.1753-6405.1993.tb00167.x . PMID   7911332.
  38. ↑ "Oxazepam".
  39. ↑ Griffiths RR, Johnson MW (2005). "Relative abuse liability of hypnotic drugs: a conceptual framework and algorithm for differentiating among compounds". The Journal of Clinical Psychiatry. 66 Suppl 9: 31–41. PMID   16336040.
  40. ↑ Bergman U, Dahl-Puustinen ML (1989). "Use of prescription forgeries in a drug abuse surveillance network". European Journal of Clinical Pharmacology. 36 (6): 621–623. doi:10.1007/BF00637747. PMID   2776820. S2CID   19770310.
  41. ↑ Griffiths RR, Wolf B (August 1990). "Relative abuse liability of different benzodiazepines in drug abusers". Journal of Clinical Psychopharmacology. 10 (4): 237–243. doi:10.1097/00004714-199008000-00002. PMID   1981067. S2CID   28209526.
  42. ↑ "List of psychotropic substances under international control" (PDF). Vienna Austria: International Narcotics Control Board. August 2003. Archived (PDF) from the original on 2005-12-05. Retrieved 2005-11-19.
  43. 1 2 "Oxazepam - International Brand Names". Drugs.com. Archived from the original on 5 January 2017. Retrieved 4 January 2017.
  44. ↑ Brodin T, Fick J, Jonsson M, Klaminder J (February 2013). "Dilute concentrations of a psychiatric drug alter behavior of fish from natural populations". Science. 339 (6121): 814–815. Bibcode:2013Sci...339..814B. doi:10.1126/science.1226850. PMID   23413353. S2CID   38518537.
  45. ↑ Hellström G, Klaminder J, Finn F, Persson L, Alanärä A, Jonsson M, et al. (December 2016). "GABAergic anxiolytic drug in water increases migration behaviour in salmon". Nature Communications. 7 (13460): 13460. Bibcode:2016NatCo...713460H. doi:10.1038/ncomms13460. PMC   5155400 . PMID   27922016.
  46. ↑ Klaminder J, Jonsson M, Leander J, Fahlman J, Brodin T, Fick J, Hellström G (October 2019). "Less anxious salmon smolt become easy prey during downstream migration". The Science of the Total Environment. 687: 488–493. Bibcode:2019ScTEn.687..488K. doi:10.1016/j.scitotenv.2019.05.488. PMID   31212157. S2CID   195065107.
  47. ↑ Lagesson A, Brodin T, Fahlman J, Fick J, Jonsson M, Persson J, et al. (February 2018). "No evidence of increased growth or mortality in fish exposed to oxazepam in semi-natural ecosystems". The Science of the Total Environment. 615: 608–614. Bibcode:2018ScTEn.615..608L. doi:10.1016/j.scitotenv.2017.09.070. PMID   28988097.
  48. ↑ Fahlman J, Hellström G, Jonsson M, Fick JB, Rosvall M, Klaminder J (March 2021). "Impacts of Oxazepam on Perch (Perca fluviatilis) Behavior: Fish Familiarized to Lake Conditions Do Not Show Predicted Anti-anxiety Response". Environmental Science & Technology. 55 (6): 3624–3633. Bibcode:2021EnST...55.3624F. doi:10.1021/acs.est.0c05587. PMC   8031365 . PMID   33663207.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.