ethyl loflazepate

{{Short description|Chemical compound}}

{{Drugbox

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 461097130

| IUPAC_name = ethyl 7-chloro-5-(2-fluorophenyl)-2-oxo-1,3-dihydro-1,4-benzodiazepine-3-carboxylate

| image = Ethyl loflazepate.svg

| image_class = skin-invert-image

| width = 222

| image2 = EtLoflazepate3d.png

| image_class2 = bg-transparent

| width2 = 190

| tradename = Victan, Meilax, Ronlax

| Drugs.com = {{drugs.com|international|ethyl-loflazepate}}

| pregnancy_category = ?

| legal_BR = B1

| legal_BR_comment = {{Cite web |author=Anvisa |author-link=Brazilian Health Regulatory Agency |date=2023-03-31 |title=RDC Nº 784 - Listas de Substâncias Entorpecentes, Psicotrópicas, Precursoras e Outras sob Controle Especial |trans-title=Collegiate Board Resolution No. 784 - Lists of Narcotic, Psychotropic, Precursor, and Other Substances under Special Control|url=https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |url-status=live |archive-url=https://web.archive.org/web/20230803143925/https://www.in.gov.br/en/web/dou/-/resolucao-rdc-n-784-de-31-de-marco-de-2023-474904992 |archive-date=2023-08-03 |access-date=2023-08-16 |publisher=Diário Oficial da União |language=pt-BR |publication-date=2023-04-04}}

| legal_CA = Schedule IV

| legal_DE = Anlage III

| legal_US = Schedule IV

| routes_of_administration = Oral

| bioavailability = ?

| metabolism = Hepatic

| elimination_half-life = 51-103 h

| excretion = Renal

| CAS_number_Ref = {{cascite|changed|??}}

| CAS_number = 29177-84-2

| ATC_prefix = N05

| ATC_suffix = BA18

| ChEMBL_Ref = {{ebicite|correct|EBI}}

| ChEMBL = 1213460

| PubChem = 3299

| DrugBank_Ref = {{drugbankcite|correct|drugbank}}

| DrugBank = DB01545

| ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}}

| ChemSpiderID = 3183

| UNII_Ref = {{fdacite|changed|FDA}}

| UNII = VJB5FW9W9J

| KEGG_Ref = {{keggcite|changed|kegg}}

| KEGG = D01293

| C=18 | H=14 | Cl=1 | F=1 | N=2 | O=3

| smiles = FC1=CC=CC=C1C2=NC(C(OCC)=O)C(NC3=C2C=C(C=C3)Cl)=O

| StdInChI_Ref = {{stdinchicite|correct|chemspider}}

| StdInChI = 1S/C18H14ClFN2O3/c1-2-25-18(24)16-17(23)21-14-8-7-10(19)9-12(14)15(22-16)11-5-3-4-6-13(11)20/h3-9,16H,2H2,1H3,(H,21,23)

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}

| StdInChIKey = CUCHJCMWNFEYOM-UHFFFAOYSA-N

}}

Ethyl loflazepate{{cite patent | country = DE | number = 2012190 }} (marketed under the brand names Meilax, Ronlax and Victan){{cite journal | vauthors = Ba BB, Iliadis A, Durand A, Berger Y, Cano JP | title = New approach in bioavailability study of two formulations of ethyl loflazepate | journal = Arzneimittel-Forschung | volume = 38 | issue = 10 | pages = 1486–1489 | date = October 1988 | pmid = 2904268 }}{{cite journal | vauthors = Ba BB, Iliadis A, Cano JP | title = Pharmacokinetic modeling of ethyl loflazepate (Victan) and its main active metabolites | journal = Annals of Biomedical Engineering | volume = 17 | issue = 6 | pages = 633–646 | year = 1989 | pmid = 2574017 | doi = 10.1007/BF02367467 | s2cid = 31310535 }}{{cite web|url=http://www.non-benzodiazepines.org.uk/benzodiazepine-names.html |title=Benzodiazepine Names |access-date=2009-04-05 |publisher=non-benzodiazepines.org.uk |url-status=dead |archive-url=https://web.archive.org/web/20081208054743/http://www.non-benzodiazepines.org.uk/benzodiazepine-names.html |archive-date=2008-12-08 }} is a drug which is a benzodiazepine derivative. It possesses anxiolytic, anticonvulsant, sedative and skeletal muscle relaxant properties.{{cite journal | vauthors = Ueki S, Watanabe S, Yamamoto T, Shibata S, Shibata K, Ohta H, Ikeda K, Kiyota Y, Sato Y | display-authors = 6 | title = [Behavioral effects of ethyl loflazepate and its metabolites] | journal = Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica | volume = 82 | issue = 5 | pages = 395–409 | date = November 1983 | pmid = 6142848 | doi = 10.1254/fpj.82.395 | doi-access = free }} In animal studies it was found to have low toxicity, although in rats evidence of pulmonary phospholipidosis occurred with pulmonary foam cells developing with long-term use of very high doses.{{cite journal | vauthors = Mazue G, Berthe J, Newmann AJ, Brunaud M | title = A toxicologic evaluation of ethyl fluclozepate (CM 6912) | journal = International Journal of Clinical Pharmacology, Therapy, and Toxicology | volume = 19 | issue = 10 | pages = 453–472 | date = October 1981 | pmid = 6116677 }} Its elimination half-life is 51–103 hours.{{cite journal | vauthors = Cautreels W, Jeanniot JP | title = Quantitative analysis of CM 6912 (ethyl loflazepate) and its metabolites in plasma and urine by chemical ionization gas chromatography mass spectrometry. Application to pharmacokinetic studies in man | journal = Biomedical Mass Spectrometry | volume = 7 | issue = 11–12 | pages = 565–571 | date = November 1980 | pmid = 6112027 | doi = 10.1002/bms.1200071124 }} Its mechanism of action is similar to other benzodiazepines. Ethyl loflazepate also produces an active metabolite which is stronger than the parent compound.{{cite journal | vauthors = Sakai Y, Namima M | title = Inhibitory effect on 3H-diazepam binding and potentiating action on GABA of ethyl loflazepate, a new minor tranquilizer | journal = Japanese Journal of Pharmacology | volume = 37 | issue = 4 | pages = 373–379 | date = April 1985 | pmid = 2861304 | doi = 10.1254/jjp.37.373 | doi-access = free }} Ethyl loflazepate was designed to be a prodrug for descarboxyloflazepate, its active metabolite. It is the active metabolite which is responsible for most of the pharmacological effects rather than ethyl loflazepate.{{cite journal | vauthors = Chambon JP, Perio A, Demarne H, Hallot A, Dantzer R, Roncucci R, Bizière K | title = Ethyl loflazepate: a prodrug from the benzodiazepine series designed to dissociate anxiolytic and sedative activities | journal = Arzneimittel-Forschung | volume = 35 | issue = 10 | pages = 1573–1577 | year = 1985 | pmid = 2866771 }} The main metabolites of ethyl loflazepate are descarbethoxyloflazepate, loflazepate and 3-hydroxydescarbethoxyloflazepate.{{cite journal | vauthors = Davi H, Guyonnet J, Sales Y, Cautreels W | title = Metabolism of ethyl loflazepate in the rat, the dog, the baboon and in man | journal = Arzneimittel-Forschung | volume = 35 | issue = 7 | pages = 1061–1065 | year = 1985 | pmid = 2864933 }} Accumulation of the active metabolites of ethyl loflazepate are not affected by those with kidney failure or impairment.{{cite journal | vauthors = Ba BB, Iliadis A, Durand A, Berger Y, Necciari J, Cano JP | title = Effect of renal failure on the pharmacokinetics of ethyl loflazepate (Victan) in man | journal = Fundamental & Clinical Pharmacology | volume = 3 | issue = 1 | pages = 11–17 | year = 1989 | pmid = 2714728 | doi = 10.1111/j.1472-8206.1989.tb00025.x | s2cid = 2850707 }} The symptoms of an overdose of ethyl loflazepate include sleepiness, agitation and ataxia. Hypotonia may also occur in severe cases. These symptoms occur much more frequently and severely in children.{{cite journal | vauthors = Pulce C, Mollon P, Pham E, Frantz P, Descotes J | title = Acute poisonings with ethyle loflazepate, flunitrazepam, prazepam and triazolam in children | journal = Veterinary and Human Toxicology | volume = 34 | issue = 2 | pages = 141–143 | date = April 1992 | pmid = 1354907 }} Death from therapeutic maintenance doses of ethyl loflazepate taken for 2 – 3 weeks has been reported in 3 elderly patients. The cause of death was asphyxia due to benzodiazepine toxicity.{{cite journal | vauthors = Kamijo Y, Hayashi I, Nishikawa T, Yoshimura K, Soma K | title = Pharmacokinetics of the active metabolites of ethyl loflazepate in elderly patients who died of asphyxia associated with benzodiazepine-related toxicity | journal = Journal of Analytical Toxicology | volume = 29 | issue = 2 | pages = 140–144 | date = March 2005 | pmid = 15902983 | doi = 10.1093/jat/29.2.140 }} High doses of the antidepressant fluvoxamine may potentiate the adverse effects of ethyl loflazepate.{{cite journal | vauthors = Imanishi T, Onozawa K, Hayashi A, Baba J | title = [Effects of fluvoxamine on both the desired anxiolytic effect and the adverse motor incoordination and amnesia induced by benzodiazepines] | journal = Nihon Yakurigaku Zasshi. Folia Pharmacologica Japonica | volume = 118 | issue = 6 | pages = 403–410 | date = December 2001 | pmid = 11778459 | doi = 10.1254/fpj.118.403 | doi-access = free }}

Ethyl loflazeplate is commercialized in Mexico, under the trade name Victan. It is officially approved for the following conditions:{{cite web| url=http://www.saludzac.gob.mx/plm/prods/36557.htm| title=Victan| access-date=2009-12-25| publisher=saludzac.gob.mx/| archive-url=https://web.archive.org/web/20090526230611/http://www.saludzac.gob.mx/plm/prods/36557.htm| archive-date=2009-05-26| url-status=dead}}{{cite web | url=http://www.famguerra.com/Meds/Search/Meds.cfm?pagina=36557.htm | title=VICTAN| access-date=2009-12-25| publisher=Farmacia Guerra}}

• Anxiety
• Post-trauma anxiety
• Anxiety associated with severe neuropathic pain
• Generalized anxiety disorder (GAD)
• Obsessive–compulsive disorder
• Panic attack
• Delirium tremens