List of benzodiazepines

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The tables below contain a sample list of benzodiazepines and benzodiazepine analogs that are commonly prescribed, with their basic pharmacological characteristics, such as half-life and equivalent doses to other benzodiazepines, also listed, along with their trade names and primary uses. The elimination half-life is how long it takes for half of the drug to be eliminated by the body. "Time to peak" refers to when maximum levels of the drug in the blood occur after a given dose. Benzodiazepines generally share the same pharmacological properties, such as anxiolytic, sedative, hypnotic, skeletal muscle relaxant, amnesic, and anticonvulsant effects. Variation in potency of certain effects may exist amongst individual benzodiazepines. Some benzodiazepines produce active metabolites. Active metabolites are produced when a person's body metabolizes the drug into compounds that share a similar pharmacological profile to the parent compound and thus are relevant when calculating how long the pharmacological effects of a drug will last. Long-acting benzodiazepines with long-acting active metabolites, such as diazepam and chlordiazepoxide, are often prescribed for benzodiazepine or alcohol withdrawal as well as for anxiety if constant dose levels are required throughout the day. Shorter-acting benzodiazepines are often preferred for insomnia due to their lesser hangover effect. [1] [2] [3] [4] [5]

Contents

It is fairly important to note that elimination half-life of diazepam and chlordiazepoxide, as well as other long half-life benzodiazepines, is twice as long in the elderly compared to younger individuals. Due to increased sensitivity and potentially dangerous adverse events among elderly patients, it is recommended to avoid prescribing them as specified by the 2015 American Geriatrics Society Beers Criteria. [6] Individuals with an impaired liver also metabolize benzodiazepines more slowly. Thus, the approximate equivalent of doses below may need to be adjusted accordingly in individuals on short acting benzodiazepines who metabolize long-acting benzodiazepines more slowly and vice versa. The changes are most notable with long acting benzodiazepines as these are prone to significant accumulation in such individuals and can lead to withdrawal symptoms.[ citation needed ] For example, the equivalent dose of diazepam in an elderly individual on lorazepam may be half of what would be expected in a younger individual. [7] [8] Equivalent doses of benzodiazepines differ as much as 20 fold. [9] [10] [11]

Pharmacokinetic properties of various benzodiazepines

Equivalency data in the table below is taken from the Ashton "Benzodiazepine Equivalence Table". [4] [12] [13] [14]

Drug NameCommon Trade Names [lower-alpha 1] Year Approved

(US FDA)

Typical Oral Dosage Formulations

(mg)

Approx. Equivalent Oral Dose to 10 mg Diazepam [lower-alpha 2] (mg)Peak Onset of Action

(hours)

Elimination Half-life of Active Metabolite (hours)Primary Therapeutic Use
Adinazolam Deracyn Research chemical 1–23 anxiolytic, antidepressant
Alprazolam Xanax, Helex, Xanor, Trankimazin, Onax, Alprox, Misar, Restyl, Solanax, Tafil, Neurol, Frontin, Kalma, Ksalol, Farmapram19810.25, 0.5, 1, 20.51–3 [16] 11-13 [10–20] [16] anxiolytic, antidepressant [17]
Bentazepam [lower-alpha 3] Thiadipona251–32–4 anxiolytic
Bretazenil [18] 2.5 anxiolytic, anticonvulsant
Bromazepam Lexotanil, Lexotan, Lexilium, Lectopam, Lexaurin, Lexatin, Bromam19811.5, 3, 661–520–40 anxiolytic,

hypnotic, muscle relaxant

Bromazolam Research chemical2 , 42 anxiolytic
Brotizolam [lower-alpha 4] Lendormin, Dormex, Sintonal, Noctilan0.250.50.5–24–5 hypnotic
Camazepam Albego, Limpidon40 [19] 1–36–11 anxiolytic
Chlordiazepoxide Librium, Risolid, Elenium19605, 10, 25251.5–636–200 anxiolytic
Cinazepam Levana0.5, 1, 22–460 hypnotic, anxiolytic
Cinolazepam Gerodorm400.5–29 hypnotic
Clobazam Onfi, Frisium, Urbanol20115, 10, 20201–58–60 anxiolytic, anticonvulsant
Clonazepam Rivatril, Rivotril, Klonopin, Iktorivil, Paxam19750.5, 1, 20.5-11–519.5–50 anticonvulsant, anxiolytic
Clonazolam Research chemical0.25, 0.50.20.5-13-4 [20] hypnotic, anticonvulsant
Clorazepate Tranxene, Tranxilium19723.75, 5, 7.515Variable32–152 anxiolytic, anticonvulsant
Clotiazepam [lower-alpha 3] Veratran, Clozan, Rize5, 10101–34 anxiolytic
Cloxazolam Cloxam, Sepazon, Olcadil1, 2, 41.5 [19] 2–555–77 [19] anxiolytic, anticonvulsant
Delorazepam Dadumir0.5, 1, 21-1.51–279< [21] anxiolytic, amnesic
Deschloroetizolam [lower-alpha 4] Research chemical1, 24 anxiolytic
Diazepam Antenex, Apaurin, Apzepam, Apozepam, Diazepan, Hexalid, Normabel, Pax, Stesolid, Stedon, Tranquirit, Valium, Vival, Valaxona19632, 5, 10101–1.532–205 anxiolytic, anticonvulsant, muscle relaxant, amnesic
Diclazepam [22] Research chemical1, 221.5–342 anxiolytic, muscle relaxant
Estazolam ProSom, Nuctalon19901, 22 [19] 3–510–24 hypnotic, anxiolytic
Ethyl carfluzepate Not approved21–511–24 hypnotic
Etizolam [lower-alpha 4] Etilaam, Etizest, Pasaden, DepasOften sold as a research chemical, but is approved for human use in many countries. Controlled substance in some US states, Canada, Germany, Austria, and others. [23] [24] 121–35-7 anxiolytic, muscle relaxant, anticonvulsant
Ethyl loflazepate Victan, Meilax, Ronlax2 [19] 2.5–373–119 anxiolytic
Flualprazolam Research chemical0.5, 10.251-212-22 anxiolytic, hypnotic
Flubromazepam [25] TemplexResearch chemical4, 8, 1241.5–8100–220 anxiolytic, hypnotic, amnesic, muscle relaxant, anticonvulsant
Flubromazolam RemnonResearch chemical0.25, 0.50.0750.5-510-20 [26] hypnotic
Fluclotizolam [lower-alpha 4] Research chemical0.25-0.5 anxiolytic
Flunitrazepam Rohypnol, Hipnosedon, Vulbegal, Fluscand, Flunipam, Ronal, Rohydorm, Hypnodorm19721, 21.50.5–318–200 hypnotic
Flunitrazolam Research chemical0.25, 0.50.10.5-15-13 hypnotic
Flurazepam Dalmadorm, Dalmane, Fluzepam19703020-251–1.540–250 hypnotic
Flutazolam Coreminal4101-347-100 hypnotic
Flutemazepam Research chemical10.5-58-20 hypnotic, anxiolytic, anticonvulsant, muscle relaxant [27]
Flutoprazepam Restas19841, 22.50.5–987 [28] hypnotic, anticonvulsant, muscle relaxant
Halazepam Alapryl, Paxipam198120, 40403–615-35 [30-100] anxiolytic
Ketazolam Anxon, Sedotime198015, 30, 45202.5–630-100 [36-200] anxiolytic
Loprazolam Dormonoct, Havlane19831, 21.52–56–20 [29] hypnotic
Lorazepam Ativan, Orfidal, Lorenin, Lorsilan, Temesta, Tavor, Lorabenz19770.5, 1, 2, 2.512–410–20 anxiolytic, anticonvulsant, hypnotic, muscle relaxant [30] [14] [31]
Lormetazepam Loramet, Noctamid, Pronoctan19841, 21.50.5–210-12 hypnotic, anxiolytic
Meclonazepam Research chemical6 anxiolytic
Medazepam Nobrium, Ansilan, Mezapam, Rudotel, Raporan10104-836–200 anxiolytic
Metizolam [lower-alpha 4] Research chemical1, 2, 42–412 anxiolytic
Mexazolam Melex, Sedoxil0.5, 11–2 anxiolytic
Midazolam Dormicum, Flormidal, Versed, Hypnovel, Dormonid19857.5, 1510 (oral)

4 (IV)

0.5–11.8-6 hypnotic, anticonvulsant
Nifoxipam Research chemical0.5, 1, 2 hypnotic
Nimetazepam Erimin, Lavol198452.5-50.5–314–30 hypnotic
Nitemazepam Research chemical20.5-510-27 hypnotic, anticonvulsant
Nitrazepam Mogadon, Alodorm, Pacisyn, Dumolid, Nitrazadon19655, 1050.5–717–48 hypnotic, anticonvulsant
Nitrazolam Research chemical0.5, 1 hypnotic
Nordazepam Madar, Stilny5, 7.5, 1510-1530–150 anxiolytic
Norflurazepam Research chemical547-100 hypnotic
Oxazepam Seresta, Serax, Serenid, Serepax, Sobril, Oxabenz, Oxapax, Oxascand, Ox-Pam, Opamox, Alepam, Medopam, Murelax, Noripam, Purata196510, 15, 30, 50303–44–11 anxiolytic
Phenazepam Phenazepam, PhenzitatResearch chemical1.5–460 anxiolytic, anticonvulsant
Pinazepam Domar, Duna5, 1040–100 anxiolytic
Prazepam Demetrin, Lysanxia, Prazene, Centrax197610, 20, 3015-202–636–200 anxiolytic
Premazepam Not approved152–610–13 anxiolytic
Pyrazolam Research chemical0.25, 0.5, 11–1.516–18 [32] anxiolytic, amnesic
Quazepam Doral, Quiedorm198515201–539–120 hypnotic
Rilmazafone Rhythmy11 hypnotic
Temazepam Restoril, Normison, Euhypnos, Temaze, Tenox198110, 2015-200.5–34–11 hypnotic, anxiolytic, muscle relaxant
Tetrazepam Myolastan, Clinoxam, Epsipam, Musaril501–33–26 muscle relaxant, anxiolytic
Triazolam Halcion, Rilamir, Notison, Somese19800.125, 0.250.50.5–22 hypnotic
Drug NameCommon Trade NamesYear ApprovedTypical Dosages of Oral Tablets

(mg)

Approx. Equivalent Oral Dose to 10mg Diazepam (mg)Peak onset of action (hours)Elimination Half-life of Active Metabolite (hours)Primary Therapeutic Use

Atypical benzodiazepine receptor ligands

Drug NameCommon Trade NamesYear approved (US FDA)Elimination Half-life of Active Metabolite (hours)Primary Therapeutic Use
DMCM anxiogenic, convulsant
Flumazenil [lower-alpha 5] Anexate, Lanexat, Mazicon, Romazicon1 antidote
Eszopiclone §Lunesta20046 hypnotic
Zaleplon §Sonata, Starnoc19991 hypnotic
Zolpidem §Ambien, Nytamel, Sanval, Stilnoct, Stilnox, Sublinox (Canada), Xolnox, Zoldem, Zolnod19922.6 hypnotic
Zopiclone §Imovane, Rhovane, Ximovan; Zileze; Zimoclone; Zimovane; Zopitan; Zorclone, Zopiklone4–6 hypnotic
  1. ↑ Not all trade names are listed.
  2. ↑ An alternative table published by the state of South Australia uses equivalent approximate oral dosages to 5 mg diazepam. [15]
  3. 1 2 Technically this is a thienodiazepine, but produces very similar effects as benzodiazepines.
  4. 1 2 3 4 5 Technically this is a thienotriazolodiazepine, but produces very similar effects as benzodiazepines.
  5. ↑ Flumazenil is an imidazobenzodiazepine derivative, [33] and in layman's terms, it is a benzodiazepine overdose antidote that is given intravenously in Intensive Care Units (ICUs) to reverse the effects of benzodiazepine overdoses, as well for overdoses of the non-benzodiazepine "Z-drugs" such as zolpidem. [34] Flumazenil is contraindicated for benzodiazepine-tolerant patients in overdose cases. [34] In such cases, the benefits are far outweighed by the risks, which include potential and severe seizures. [33] [35] The method by which flumazenil acts to prevent non-benzodiazepine tolerant overdose from causing potential harm is via preventing the benzodiazepines and Z-drugs from binding to the GABAA receptors via competitive inhibition which the flumazenil creates. Clinical observation notating the patient's oxygen levels, respiratory, heart and blood pressure rates are used, as they are much safer than the potential seizure effects from flumazenil. Supportive care to mediate any problems resulting from abnormal rates of the pulmonary, respiratory, and cardiovascular systems is typically the only treatment that is required in benzodiazepine-only overdoses. [36] In most cases, activated charcoal/carbon is often used to prevent benzodiazepines from being absorbed by the gastrointestinal tract, and the use of stomach-pumping/gastric lavage is no longer commonly used nor suggested by some toxicologists. [37] Even in cases where other central nervous system (CNS) depressants (such as in combined benzodiazepine and tricyclic antidepressant/TCA overdoses) are detected and/or suspected, endotrachial intubation for the airway path and supportive oxygen are typically implemented and are much safer than flumazenil. [36]

Controversy

In 2015 the UK's House of Commons attempted to get a two to four week limit mandate for prescribing benzodiazepines to replace the two to four week benzodiazepine prescribing guidelines, which are merely recommended. [38]

Binding data and structure-activity relationship

A variety of Benzodiazepines along with their molecular structure. Benzodiazepines en France.jpg
A variety of Benzodiazepines along with their molecular structure.

A large number of benzodiazepine derivatives have been synthesised and their structure-activity relationships explored in detail. [39] [40] [41] [42] This chart contains binding data for benzodiazepines and related drugs investigated by Roche up to the late 1990s (though in some cases the compounds were originally synthesised by other companies such as Takeda or Upjohn). [43] [44] [45] [46] [47] [48] Other benzodiazepines are also listed for comparison purposes, [49] [50] [51] but it does not however include binding data for;

While binding or activity data are available for most of these compounds also, the assay conditions vary between sources, meaning that in many cases the values are not suitable for a direct comparison. Many older sources used animal measures of activity (i.e. sedation or anticonvulsant activity) but did not measure in vitro binding to benzodiazepine receptors. [57] [58] See for instance Table 2 vs Table 11 in the Chem Rev paper, Table 2 lists in vitro pIC50 values matching those below, while Table 11 has pEC50 values derived from in vivo assays in mice, which show the same activity trends but cannot be compared directly, and includes data for compounds such as diclazepam and flubromazepam which are not available in the main data set.


Also note;

Table

See also

Related Research Articles

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

Benzodiazepines, colloquially called "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">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">Zolpidem</span> Hypnotic medication

Zolpidem, sold under the brand name Ambien among others, is a medication primarily used for the short-term treatment of sleeping problems. Guidelines recommend that it be used only after cognitive behavioral therapy for insomnia and after behavioral changes, such as sleep hygiene, have been tried. It decreases the time to sleep onset by about fifteen minutes and at larger doses helps people stay asleep longer. It is taken by mouth and is available in conventional tablets, sublingual tablets, or oral spray.

<span class="mw-page-title-main">Flumazenil</span> GABA receptor antagonist drug and benzodiazepine antidote

Flumazenil is a selective GABAA receptor antagonist administered via injection, otic insertion, or intranasally. Therapeutically, it acts as both an antagonist and antidote to benzodiazepines, through competitive inhibition.

<span class="mw-page-title-main">Zopiclone</span> Hypnotic medication

Zopiclone, sold under the brand name Imovane among others, is a nonbenzodiazepine, specifically a cyclopyrrolone, used to treat difficulty sleeping. Zopiclone is molecularly distinct from benzodiazepine drugs and is classed as a cyclopyrrolone. However, zopiclone increases the normal transmission of the neurotransmitter gamma-aminobutyric acid (GABA) in the central nervous system, via modulating GABAA receptors similarly to the way benzodiazepine drugs do inducing sedation but not with the anti-anxiety properties of the benzodiazepines.

<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">Eszopiclone</span> Hypnotic medication

Eszopiclone, sold under the brand name Lunesta among others, is a medication used in the treatment of insomnia. Evidence supports slight to moderate benefit up to six months. It is taken by mouth.

<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">Alpidem</span> Anxiolytic medication

Alpidem, sold under the brand name Ananxyl, is a nonbenzodiazepine anxiolytic medication which was briefly used to treat anxiety disorders but is no longer marketed. It was previously marketed in France, but was discontinued due to liver toxicity. Alpidem is taken by mouth.

<span class="mw-page-title-main">Adinazolam</span> Triazolobenzodiazepine drug

Adinazolam is a tranquilizer of the triazolobenzodiazepine (TBZD) class, which are benzodiazepines (BZDs) fused with a triazole ring. It possesses anxiolytic, anticonvulsant, sedative, and antidepressant properties. Adinazolam was developed by Jackson B. Hester, who was seeking to enhance the antidepressant properties of alprazolam, which he also developed. Adinazolam was never FDA approved and never made available to the public market; however, it has been sold as a designer drug.

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

Etizolam is a thienodiazepine derivative which is a benzodiazepine analog. The etizolam molecule differs from a benzodiazepine in that the benzene ring has been replaced by a thiophene ring and triazole ring has been fused, making the drug a thienotriazolodiazepine.

<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">Ro15-4513</span> Chemical compound

Ro15-4513(IUPAC: Ethyl-8-azido-5,6-dihydro-5-methyl-6-oxo-4H-imidazo-1,4-benzodiazepine-3-carboxylate) is a weak partial inverse agonist of the benzodiazepine class of drugs, developed by Hoffmann–La Roche in the 1980s. It acts as an inverse agonist, and can therefore be an antidote to the acute impairment caused by alcohols, including ethanol, isopropanol, tert-butyl alcohol, tert-amyl alcohol, 3-methyl-3-pentanol, methylpentynol and ethchlorvynol.

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

Imidazenil is an experimental anxiolytic drug which is derived from the benzodiazepine family, and is most closely related to other imidazobenzodiazepines such as midazolam, flumazenil, and bretazenil.

<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">Pyrazolam</span> Benzodiazepine

Pyrazolam (SH-I-04) is a benzodiazepine derivative originally developed by a team led by Leo Sternbach at Hoffman-La Roche in the 1970s. It has since been "rediscovered" and sold as a designer drug since 2012.‹The template Excessive citations inline is being considered for deletion.› 

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

Diclazepam (Ro5-3448), also known as chlorodiazepam and 2'-chloro-diazepam, is a benzodiazepine and functional analog of diazepam. It was first synthesized by Leo Sternbach and his team at Hoffman-La Roche in 1960. It is not currently approved for use as a medication, but rather sold as an unscheduled substance. Efficacy and safety have not been tested in humans.

<span class="mw-page-title-main">Flubromazolam</span> Triazolobenzodiazepine drug

Flubromazolam (JYI-73) is a triazolobenzodiazepine (TBZD), which are benzodiazepine (BZD) derivatives. Flubromazolam is reputed to be highly potent, and concerns have been raised that clonazolam and flubromazolam in particular may pose comparatively higher risks than other designer benzodiazepines, due to their ability to produce strong sedation and amnesia at oral doses of as little as 0.5 mg. Life-threatening adverse reactions have been observed at doses of only 3 mg of flubromazolam.

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

Desmethylflunitrazepam (also known as norflunitrazepam, Ro05-4435 and fonazepam) is a benzodiazepine that is a metabolite of flunitrazepam and has been sold online as a designer drug. It has an IC50 value of 1.499 nM for the GABAA receptor.

References

  1. ↑ Golombok S, Lader M (August 1984). "The psychopharmacological effects of premazepam, diazepam and placebo in healthy human subjects". British Journal of Clinical Pharmacology. 18 (2): 127–133. doi:10.1111/j.1365-2125.1984.tb02444.x. PMC   1463527 . PMID   6148956.
  2. ↑ de Visser SJ, van der Post JP, de Waal PP, Cornet F, Cohen AF, van Gerven JM (January 2003). "Biomarkers for the effects of benzodiazepines in healthy volunteers". British Journal of Clinical Pharmacology. 55 (1): 39–50. doi:10.1046/j.1365-2125.2002.t01-10-01714.x. PMC   1884188 . PMID   12534639.
  3. ↑ "Benzodiazepine Names". non-benzodiazepines.org.uk. Archived from the original on 2008-12-08. Retrieved 2009-04-05.
  4. 1 2 Ashton CH (March 2007). "Benzodiazepine Equivalence Table". benzo.org.uk. Retrieved 2009-04-05.
  5. ↑ Hsiung R (July 1995). "Benzodiazepine Equivalence Charts". dr-bob.org. Archived from the original on 2009-02-09. Retrieved 2009-04-05.
  6. ↑ By the American Geriatrics Society 2015 Beers Criteria Update Expert Panel; et al. (American Geriatrics Society 2015 Beers Criteria Update Expert Panel) (November 2015). "American Geriatrics Society 2015 Updated Beers Criteria for Potentially Inappropriate Medication Use in Older Adults". Journal of the American Geriatrics Society. 63 (11): 2227–2246. doi: 10.1111/jgs.13702 . PMID   26446832. S2CID   38797655.{{cite journal}}: CS1 maint: numeric names: authors list (link)
  7. ↑ Salzman C (15 May 2004). Clinical geriatric psychopharmacology (4th ed.). USA: Lippincott Williams & Wilkins. pp. 450–453. ISBN   978-0-7817-4380-8.
  8. ↑ Delcò F, Tchambaz L, Schlienger R, Drewe J, Krähenbühl S (2005). "Dose adjustment in patients with liver disease". Drug Safety. 28 (6): 529–545. doi:10.2165/00002018-200528060-00005. PMID   15924505. S2CID   9849818.
  9. ↑ Riss J, Cloyd J, Gates J, Collins S (August 2008). "Benzodiazepines in epilepsy: pharmacology and pharmacokinetics". Acta Neurologica Scandinavica. 118 (2): 69–86. doi: 10.1111/j.1600-0404.2008.01004.x . PMID   18384456. S2CID   24453988.
  10. ↑ Ashton H (July 1994). "Guidelines for the rational use of benzodiazepines. When and what to use". Drugs. 48 (1): 25–40. doi:10.2165/00003495-199448010-00004. PMID   7525193. S2CID   46966796.
  11. ↑ "benzo.org.uk : Benzodiazepines: How They Work & How to Withdraw, Prof C H Ashton DM, FRCP, 2002". benzo.org.uk. Retrieved 2019-12-19.
  12. ↑ "Benzodiazepine Equivalence Chart". www.mental-health-today.com. Archived from the original on 30 January 2023.
  13. ↑ "Benzodiazepine Equivalence Table". www.bcnc.org.uk. April 2007. Archived from the original on 2015-02-06.
  14. 1 2 Farinde A (31 July 2018). "Benzodiazepine Equivalency Table". Medscape.
  15. ↑ "Benzodiazepines Information for GPs" (PDF). Drug and Alcohol Services South Australia.
  16. 1 2 Moylan S, Giorlando F, Nordfjærn T, Berk M (March 2012). "The role of alprazolam for the treatment of panic disorder in Australia". The Australian and New Zealand Journal of Psychiatry. 46 (3): 212–224. doi:10.1177/0004867411432074. PMID   22391278. S2CID   11006795.
  17. ↑ Ashton Manual
  18. ↑ van Steveninck AL, Gieschke R, Schoemaker RC, Roncari G, Tuk B, Pieters MS, et al. (June 1996). "Pharmacokinetic and pharmacodynamic interactions of bretazenil and diazepam with alcohol". British Journal of Clinical Pharmacology. 41 (6): 565–573. doi:10.1046/j.1365-2125.1996.38514.x. PMC   2042631 . PMID   8799523.
  19. 1 2 3 4 5 "Benzodiazepine Names". non-benzodiazepines.org.uk. Archived from the original on 2008-12-08. Retrieved 2009-05-31.
  20. ↑ N. Edinoff, Amber; A. Nix, Catherine; S. Odisho, Amira; P. Babin, Caroline; G. Derouen, Alyssa; C. Lutfallah, Salim; M. Cornett, Elyse; Murnane, Kevin S.; M. Kaye, Adam (22 August 2022). Müller, Thomas; Yamauchi, Junji (eds.). "Novel Designer Benzodiazepines: Comprehensive Review of Evolving Clinical and Adverse Effects". Neurology International. 14 (3): 652. doi: 10.3390/neurolint14030053 . PMC   9397074 . PMID   35997362.
  21. ↑ "NMS Labs Report" (PDF). NMS Labs. Retrieved 19 April 2022.
  22. ↑ Moosmann B, Bisel P, Auwärter V (2014). "Characterization of the designer benzodiazepine diclazepam and preliminary data on its metabolism and pharmacokinetics". Drug Testing and Analysis. 6 (7–8): 757–763. doi:10.1002/dta.1628. PMID   24604775.
  23. ↑ Health Santé Canada, Federal Government of Canada (January 20, 2012). "Status Decision of Controlled and Non-Controlled Substances" (PDF). Controlled Drugs and Substances Act. 1: 2.
  24. ↑ Indiana General Assembly. "House Bill 1019 - Controlled substances". Indiana General Assembly. Retrieved 2018-02-22.
  25. ↑ Moosmann B, Huppertz LM, Hutter M, Buchwald A, Ferlaino S, Auwärter V (November 2013). "Detection and identification of the designer benzodiazepine flubromazepam and preliminary data on its metabolism and pharmacokinetics". Journal of Mass Spectrometry. 48 (11): 1150–1159. Bibcode:2013JMSp...48.1150M. doi:10.1002/jms.3279. PMID   24259203.
  26. ↑ Huppertz LM, Moosmann B, Auwärter V (January 2018). "Flubromazolam - Basic pharmacokinetic evaluation of a highly potent designer benzodiazepine". Drug Testing and Analysis. 10 (1): 206–211. doi:10.1002/dta.2203. PMID   28378533.
  27. ↑ Esmailian M, Ahmadi O, Taheri M, Zamani M (September 2015). "Comparison of haloperidol and midazolam in restless management of patients referred to the Emergency Department: A double-blinded, randomized clinical trial". Journal of Research in Medical Sciences. 20 (9): 844–849. doi:10.1002/14651858.CD003079.pub4. PMC   6486117 . PMID   29219171.
  28. ↑ Barzaghi N, Leone L, Monteleone M, Tomasini G, Perucca E (1989). "Pharmacokinetics of flutoprazepam, a novel benzodiazepine drug, in normal subjects". European Journal of Drug Metabolism and Pharmacokinetics. 14 (4): 293–298. doi:10.1007/BF03190114. PMID   2633923. S2CID   20710732.
  29. ↑ Swift CG, Swift MR, Ankier SI, Pidgen A, Robinson J (August 1985). "Single dose pharmacokinetics and pharmacodynamics of oral loprazolam in the elderly". British Journal of Clinical Pharmacology. 20 (2): 119–128. doi:10.1111/j.1365-2125.1985.tb05041.x. PMC   1400680 . PMID   2864049.
  30. ↑ Shah D, Borrensen D (2011). "Benzodiazepines: A Guide to Safe Prescribing" (PDF). The Carlat Report: Psychiatry. Archived from the original (PDF) on 2015-07-01. Retrieved 2015-06-28.
  31. ↑ Vancouver Hospital Pharmaceutical Sciences. "Comparison of Benzodiazepines".
  32. ↑ Moosmann B, Hutter M, Huppertz LM, Auwärter V. "Characterization of the designer benzodiazepines pyrazolam and flubromazepam and study on their detectability in human serum and urine samples" (PDF). Archived from the original (PDF) on 2014-11-05. Retrieved 2014-11-05.
  33. 1 2 "Romazicon 2 (flumazenil) 3 Injection" (PDF). Genentech, Inc.
  34. 1 2 "Flumazenil Injection, Solution [App Pharmaceuticals, Llc]". DailyMed. U.S. National Library of Medicine. Retrieved 2014-08-15.
  35. ↑ Fleisher GR, Ludwig S, Silverman BK (2002). Synopsis of pediatric emergency medicine. Lippincott Williams & Wilkins. p. 409. ISBN   978-0-7817-3274-1.
  36. 1 2 "Toxicological analyses" . Retrieved 21 March 2013.
  37. ↑ Vale JA, Kulig K (2004). "Position paper: gastric lavage". Journal of Toxicology. Clinical Toxicology. 42 (7): 933–943. doi:10.1081/CLT-200045006. PMID   15641639. S2CID   29957973.
  38. ↑ "APPG for Involuntary Tranquilliser Addiction". benzo.org.uk. Retrieved 21 March 2015.
  39. ↑ Sternbach LH (January 1979). "The benzodiazepine story". Journal of Medicinal Chemistry. 22 (1): 1–7. doi:10.1021/jm00187a001. PMID   34039.
  40. ↑ Hadjipavlou-Litina D, Hansch C (1994). "Quantitative structure-activity relationships of the benzodiazepines. a review and reevaluation". Chemical Reviews. 94 (6): 1483–1505. doi:10.1021/cr00030a002.
  41. ↑ Edinoff AN, Nix CA, Odisho AS, Babin CP, Derouen AG, Lutfallah SC, Cornett EM, Murnane KS, Kaye AM, Kaye AD. Novel Designer Benzodiazepines: Comprehensive Review of Evolving Clinical and Adverse Effects. Neurol Int. 2022 Aug 22;14(3):648-663. doi : 10.3390/neurolint14030053 PMID   35997362
  42. ↑ Yu X, Greenblatt HK, Greenblatt DJ. Designer benzodiazepines: an update. Expert Rev Clin Pharmacol. 2023 Feb;16(2):109-117. doi : 10.1080/17512433.2023.2170349 PMID   36649662
  43. ↑ Haefely W, Kyburz E, Gerecke M, Mohler H (1985). "Recent advances in the molecular pharmacology of benzodiazepine receptors and in the structure-activity relationships of their agonists and antagonists". Adv. Drug Res. 1985 (14): 165–322.
  44. ↑ Winkler DA, Burden FR, Watkins AJ (January 1998). "Atomistic Topological Indices Applied to Benzodiazepines using Various Regression Methods". Quantitative Structure-Activity Relationships. 17 (1): 14–19. doi:10.1002/(SICI)1521-3838(199801)17:01<14::AID-QSAR14>3.0.CO;2-U.
  45. ↑ Thakur A, Thakur M, Khadikar P (November 2003). "Topological modeling of benzodiazepine receptor binding". Bioorganic & Medicinal Chemistry. 11 (23): 5203–5207. doi:10.1016/j.bmc.2003.08.014. PMID   14604684.
  46. ↑ So SS, Karplus M (December 1996). "Genetic neural networks for quantitative structure-activity relationships: improvements and application of benzodiazepine affinity for benzodiazepine/GABAA receptors". Journal of Medicinal Chemistry. 39 (26): 5246–5256. doi:10.1021/jm960536o. PMID   8978853.
  47. ↑ Braestrup C, Nielsen M (1983). "Benzodiazepine receptors. Biochemical Studies of CNS Receptors". In Iversen LL, Iversen SD, Snyder SH (eds.). Handbook of Psychopharmacology. Springer. ISBN   9781468443615.
  48. ↑ Zhang W, Diaz-Arauzo H, Allen MS, Koehler KF, Cook JM (1996). "Chapter 7: Chemical and computer assisted development of the inclusive pharmacophore of benzodiazepine receptors.". In Choudhary MI (ed.). Studies in Medicinal Chemistry. CRC Press. p. 303. ISBN   9783718658794.
  49. ↑ Obradović AL, Joksimović S, Poe MM, Ramerstorfer J, Varagic Z, Namjoshi O, et al. (March 2014). "Sh-I-048A, an in vitro non-selective super-agonist at the benzodiazepine site of GABAA receptors: the approximated activation of receptor subtypes may explain behavioral effects". Brain Research. 1554: 36–48. doi:10.1016/j.brainres.2014.01.036. PMC   3996760 . PMID   24472579.
  50. ↑ Cornett EM, Novitch MB, Brunk AJ, Davidson KS, Menard BL, Urman RD, Kaye AD (June 2018). "New benzodiazepines for sedation". Best Practice & Research. Clinical Anaesthesiology. 32 (2): 149–164. doi:10.1016/j.bpa.2018.06.007. PMID   30322456. S2CID   53501694.
  51. ↑ Clayton T, Poe MM, Rallapalli S, Biawat P, Savić MM, Rowlett JK, et al. (2015). "A Review of the Updated Pharmacophore for the Alpha 5 GABA(A) Benzodiazepine Receptor Model". International Journal of Medicinal Chemistry. 2015: 430248. doi: 10.1155/2015/430248 . PMC   4657098 . PMID   26682068.
  52. ↑ Moosmann B, King LA, Auwärter V (June 2015). "Designer benzodiazepines: A new challenge". World Psychiatry. 14 (2): 248. doi:10.1002/wps.20236. PMC   4471986 . PMID   26043347.
  53. ↑ Moosmann B, Auwärter V (2018). "Designer Benzodiazepines: Another Class of New Psychoactive Substances". In Maurer H, Brandt S (eds.). New Psychoactive Substances. Handbook of Experimental Pharmacology. Vol. 252. pp. 383–410. doi:10.1007/164_2018_154. ISBN   978-3-030-10560-0. PMID   30367253.
  54. ↑ Manchester KR, Lomas EC, Waters L, Dempsey FC, Maskell PD (January 2018). "The emergence of new psychoactive substance (NPS) benzodiazepines: A review". Drug Testing and Analysis. 10 (1): 37–53. doi: 10.1002/dta.2211 . PMID   28471096.
  55. ↑ Waters L, Manchester KR, Maskell PD, Haegeman C, Haider S (May 2018). "The use of a quantitative structure-activity relationship (QSAR) model to predict GABA-A receptor binding of newly emerging benzodiazepines". Science & Justice. 58 (3): 219–225. doi:10.1016/j.scijus.2017.12.004. PMID   29685303.
  56. ↑ Zawilska JB, Wojcieszak J (July 2019). "An expanding world of new psychoactive substances-designer benzodiazepines". Neurotoxicology. 73: 8–16. doi:10.1016/j.neuro.2019.02.015. PMID   30802466. S2CID   73461430.
  57. ↑ Blair T, Webb GA (September 1977). "Electronic factors in the structure-activity relationship of some 1,4-benzodiazepin-2-ones". Journal of Medicinal Chemistry. 20 (9): 1206–1210. doi:10.1021/jm00219a019. PMID   926122.
  58. ↑ Biagi GL, Barbaro AM, Guerra MC, Babbini M, Gaiardi M, Bartoletti M, Borea PA (February 1980). "Rm values and structure-activity relationship of benzodiazepines". Journal of Medicinal Chemistry. 23 (2): 193–201. doi:10.1021/jm00176a016. PMID   7359533.
  59. ↑ Catalani V, Floresta G, Botha M, Corkery JM, Guirguis A, Vento A, Abbate V, Schifano F. In silico studies on recreational drugs: 3D quantitative structure activity relationship prediction of classified and de novo designer benzodiazepines. Chem Biol Drug Des. 2023 Jan;101(1):40-51. doi : 10.1111/cbdd.14119 PMID   35838189
  60. ↑ Spencer J, Rathnam RP, Chowdhry BZ (September 2010). "1,4-Benzodiazepin-2-ones in medicinal chemistry". Future Medicinal Chemistry. 2 (9): 1441–1449. doi:10.4155/fmc.10.226. PMID   21426139.

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