| 词条 | Etizolam |
| 释义 |
| Verifiedfields = changed | Watchedfields = changed | verifiedrevid = 443854261 | IUPAC_name = 4-(2-Chlorophenyl)-2-ethyl-9-methyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine | tradename = Etilaam, Etizest | image = Etizolam.svg | width = 150 | image2= EtizXtal3.png | KEGG_Ref = {{keggcite|correct|kegg}} | KEGG = D01514 | ChemSpiderID = 3191 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | smiles = ClC1=CC=CC=C1C2=NCC3=NN=C(C)N3C4=C2C=C(CC)S4 | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C17H15ClN4S/c1-3-11-8-13-16(12-6-4-5-7-14(12)18)19-9-15-21-20-10(2)22(15)17(13)23-11/h4-8H,3,9H2,1-2H3 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = VMZUTJCNQWMAGF-UHFFFAOYSA-N | UNII = A76XI0HL37 | UNII_Ref = {{fdacite|correct|FDA}} | CAS_number_Ref = {{cascite|correct|??}} | CAS_number=40054-69-1 | ATC_prefix=N05 | ATC_suffix=BA19 | ATC_supplemental = | PubChem = 3307 | ChEMBL_Ref = {{ebicite|changed|EBI}} | ChEMBL = 1289779 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank= | C=17 | H=15 | Cl=1 | N=4 | S=1 | molecular_weight = 342.07 g/mol | bioavailability= 93% | metabolism = Hepatic | elimination_half-life = 6.2 hours[1] (main metabolite is 8.2 hours) | excretion = Renal | pregnancy_category = | legal_DE = Anlage III | legal_US = Schedule I | legal_US_comment = in Alabama, Arkansas, Florida, Louisiana, Mississippi, Ohio, and Virginia; Schedule IV in Georgia, and Texas; Scheduled in Arizona[2] and Indiana;[3] not FDA approved. Unscheduled in the remaining states. | legal_UK = Class C | dependency_liability = Moderate | routes_of_administration= Oral, sublingual, rectal |drug_name=|alt=|caption=|type=|MedlinePlus=|legal_status=|licence_EU=|pregnancy_AU=|pregnancy_US=|licence_US=}}Etizolam (marketed under many brand names) is a thienodiazepine derivative [4] which is a benzodiazepine analog.[5] The etizolam molecule differs from a benzodiazepine in that the benzene ring has been replaced by a thiophene ring and triazole ring has been fused, making the drug a thienotriazolodiazepine.[6][7] It possesses amnesic, anxiolytic, anticonvulsant, hypnotic, sedative and skeletal muscle relaxant properties.[8] It was patented in 1972[9] and approved for medical use in 1983.[10] {{TOC limit}}Medical uses
Side effects
Tolerance, dependence and withdrawalAbrupt or rapid discontinuation from etizolam, as with benzodiazepines, may result in the appearance of the benzodiazepine withdrawal syndrome, including rebound insomnia.[14] Neuroleptic malignant syndrome, a rare event in benzodiazepine withdrawal, has been documented in a case of abrupt withdrawal from etizolam.[15] This is particularly relevant given etizolam's short half life relative to benzodiazepines such as diazepam resulting in a more rapid drug level decrease in blood plasma levels.[16] In a study that compared the effectiveness of etizolam, alprazolam, and bromazepam for the treatment of generalized anxiety disorder, all three drugs retained their effectiveness over 2 weeks, but etizolam became more effective from 2 weeks to 4 weeks, a type of reverse tolerance.[17] Administering .5 mg etizolam twice daily did not induce cognitive deficits over 3 weeks when compared to placebo.[18] When multiple doses of etizolam, or lorazepam, were administered to rat neurons, lorazepam caused downregulation of alpha-1 benzodiazepine binding sites (tolerance/dependence), while etizolam caused an increase in alpha-2 benzodiazepine binding sites (reverse tolerance to anti-anxiety effects).[19] Tolerance to the anticonvulsant effects of lorazepam was observed, but no significant tolerance to the anticonvulsant effects of etizolam was observed.[19] Etizolam therefore has a reduced liability to induce tolerance, and dependence, compared with classic benzodiazepines.[19] PharmacologyEtizolam, a thienodiazepine derivative, is absorbed fairly rapidly, with peak plasma levels achieved between 30 minutes and 2 hours. It has a mean elimination half life of about 3.5 hours.[20] Etizolam possesses potent hypnotic properties,[21] and is comparable with other short-acting benzodiazepines.[20] Etizolam acts as a full agonist at the benzodiazepine receptor to produce its range of therapeutic and adverse effects.[22] According to the Italian P.I. sheet{{Citation needed|date=March 2015}}, etizolam belongs to a new class of diazepines, thienotriazolodiazepines. This new class is easily oxidized, rapidly metabolized, and has a lower risk of accumulation, even after prolonged treatment. Etizolam has an anxiolytic action about 6 times greater than that of diazepam. Etizolam produces, especially at higher dosages, a reduction in time taken to fall asleep, an increase in total sleep time, and a reduction in the number of awakenings. During tests, there were no substantial changes in deep sleep; however, it may reduce REM sleep. In EEG tests of healthy volunteers, etizolam showed some similar characteristics to tricyclic antidepressants.[1] InteractionsItraconazole and fluvoxamine slow down the rate of elimination of etizolam, leading to accumulation of etizolam, therefore increasing its pharmacological effects.[23][24] Carbamazepine speeds up the metabolism of etizolam, resulting in reduced pharmacological effects.[25]Overdose{{See also|Benzodiazepine overdose}}Cases of intentional suicide by overdose using etizolam in combination with GABA agonists have been reported.[26][27] Although etizolam has a lower LD50 than certain benzodiazepines, the LD50 is still far beyond the prescribed or recommended dose. Flumazenil, a GABA antagonist agent used to reverse benzodiazepine overdoses, inhibits the effect of etizolam as well as classical benzodiazepines such as diazepam and chlordiazepoxide.[28] Society and cultureBrand namesEtilaam, Etizola, Sedekopan, Etizest, Pasaden or Depas Legal statusAustraliaEtizolam is a Schedule 4 substance under the Poisons Standard June 2018 as it is classed as a benzodiazepine derivative.[29] A schedule 4 drug is outlined in the Poisons Act 1964 as "Substances, the use or supply of which should be by or on the order of persons permitted by State or Territory legislation to prescribe and should be available from a pharmacist on prescription." [29] DenmarkEtizolam is controlled in Denmark under the Danish Misuse of Drugs Act.[30] GermanyEtizolam was controlled in Germany in July 2013.[31] ItalyEtizolam is licensed for the treatment of anxiety, insomnia and neurosis as a prescription-only medication.[32] JapanEtizolam also called Depas, is restricted as a benzodiazepine analog in Japan from October 2016 onwards. United KingdomIn the UK, etizolam has been classified as a Class C drug by the May 2017 amendment to The Misuse of Drugs Act 1971 along with several other designer benzodiazepine drugs.[33] United StatesEtizolam is not authorized by the FDA for medical use in the U.S. However, it currently remains unscheduled and is legal for research purposes. As of March 2016, etizolam is a controlled substance in the following states: Alabama[34], Arkansas,[35] Florida,[36] Georgia,[37] Louisiana, Mississippi,[38] Texas{{Failed verification|date=August 2018}}, South Carolina[39] and Virginia.[40] It is controlled in Indiana as of July 1, 2017.[3] It is controlled in Ohio as of February 2018. Abuse{{See also|Benzodiazepine misuse}}Etizolam is a drug of potential abuse. Cases of etizolam dependence have been documented in the medical literature.[41] However, conflicting reports from the World Health Organization, made public in 1991, dispute the abuse claims.[42] Since 1991, cases of etizolam abuse and addiction have substantially increased,[43] due to varying levels of accessibility and cultural popularity.[44] See also{{Div col}}
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Placement of Chemicals in Schedule I | publisher=Commonwealth of Virginia | date=2 December 2015 | language=English | accessdate= 11 March 2016}} 41. ^{{cite journal |vauthors=Gupta S, Garg B | year = 2014 | title = A case of etizolam dependence| journal = Indian J Pharmacol | volume = 46 | issue = 6| pages = 655–656 | pmc=4264086 | pmid=25538342 | doi=10.4103/0253-7613.144943}} 42. ^WHO Expert Committee on Drug Dependence 43. ^https://www.bbc.com/news/uk-scotland-43822454 44. ^https://www.pharmaceutical-journal.com/opinion/insight/novel-psychoactive-substances-understanding-the-new-illegal-drug-market/20205503.article?firstPass=false External links
5 : Chloroarenes|Designer drugs|GABAA receptor positive allosteric modulators|Hypnotics|Thienotriazolodiazepines |
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