flutemazepam

{{Short description|Chemical compound}}

{{Infobox drug

| Verifiedfields = changed

| Watchedfields = changed

| verifiedrevid = 477394733

| IUPAC_name = 7-chloro-5-(2-fluorophenyl)-3-hydroxy-1-methyl-3H-1,4-benzodiazepin-2-one

| image = Flutemazepam structure.svg

| image_class = skin-invert-image

| width = 200

| tradename =

| pregnancy_AU =

| pregnancy_US =

| pregnancy_category =

| legal_CA = Schedule IV

| legal_DE = NpSG

| legal_UK = PSA

| bioavailability =

| metabolism =

| elimination_half-life =

| excretion =

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

| CAS_number = 52391-89-6

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

| ChEMBL = 291770

| PubChem = 40344

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

| UNII_Ref = {{fdacite|correct|FDA}}

| UNII = J8U5694BCW

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

| ChemSpiderID = 36859

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

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

| StdInChI = 1S/C16H12ClFN2O2/c1-20-13-7-6-9(17)8-11(13)14(19-15(21)16(20)22)10-4-2-3-5-12(10)18/h2-8,15,21H,1H3

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

| StdInChIKey = RMFYWNFETXNTIQ-UHFFFAOYSA-N

| C=16 | H=12 | Cl=1 | F=1 | N=2 | O=2

}}

Flutemazepam was initially first synthesized in 1965, but was not further described until a team at Stabilimenti Chimici Farmaceutici Riuniti SpA in the mid-1970s.{{cite patent | country = GB | number = 1431282 | title = Benzodiazepine Compounds for Therapeutical Use | assign = Schiapparelli Farma SpA | gdate = 7 April 1976 }}{{Cite web | work = PubChem |title=Flutemazepam |url=https://pubchem.ncbi.nlm.nih.gov/compound/40344 |access-date=2022-03-31 |publisher = National Library of Medicine |language=en}} It is a short-acting (9–25 hr elimination half-life) fluorinated analogue of temazepam that has powerful hypnotic, sedative, amnesiac, anxiolytic, anticonvulsant and skeletal muscle relaxant properties. As a result, flutemazepam has been shown to have similar pharmacological properties to temazepam. It has been found to be effective for the treatment of the most severe states of anxiety, panic attacks, and insomnia. Furthermore, it is potent with 1 mg of flutemazepam being equivalent to 10 mg of diazepam.{{cite web |title=Flutemazepam |url=https://www.usbio.net/biochemicals/450249/Flutemazepam/data-sheet |website=US Biologic |publisher=United States Biological |access-date=22 July 2022}}{{Cite web |title=Temazepam Oral: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing - WebMD |url=https://www.webmd.com/drugs/2/drug-8715/temazepam-oral/details |access-date=2022-03-31 |website=www.webmd.com |language=en}}{{cite web |url=http://www.psychotropics.dk/moleculeView/default.aspx?ID=1409&Catalogtype=A&ChapterID=1&Thissortorder=5 |title=flutemazepam |access-date=11 February 2009 |publisher=psychotropics.dk}}{{cite book | vauthors = Morton IK, Hall JM | title = Concise Dictionary of Pharmacological Agents | publisher = Springer | date = 1999 | isbn = 978-0-7514-0499-9 }} Flutemazepam is highly effective for acute psychotic states, especially stimulant psychosis, violent behaviour, and aggression.{{cite journal |vauthors=Esmailian M, Ahmadi O, Taheri M, Zamani M | title = Comparison of haloperidol and midazolam in restless management of patients referred to the Emergency Department: A double-blinded, randomized clinical trial | journal = Journal of Research in Medical Sciences | volume = 20 | issue = 9 | pages = 844–849 | date = September 2015 | pmc = 6486117 | doi = 10.1002/14651858.CD003079.pub4 | pmid = 29219171 }}

It was first synthesized and described in 1965 by Leo Sternbach.{{cite web |title=PubChem Compound Summary for CID 40344, Flutemazepam |url=https://pubchem.ncbi.nlm.nih.gov/compound/40344 |publisher=National Center for Biotechnology Information (2022) |access-date=30 July 2022}} In a test which compared a series of 3-fluorobenzodiazepine compounds in 1976, one of which was the 3-hydroxy benzodiazepine, flutemazepam. There were nine compounds tested (all nine were 3-fluorobenzodiazepines) including, a well known compound known as N-Desalkyl-3-hydroxyflurazepam, or also called norflurazepam ). Flutemazepam was the most potent: 20x more potent than temazepam, 10x more potent than diazepam and nitrazepam, and roughly equipotent to a related 3-hydroxy benzodiazepine, lorazepam. Equipotent to another fluorinated analogue (of nitrazepam), flunitrazepam. Via oral administration, 1 mg flutemazepam is equivalent to 10 mg diazepam. Of the nine compounds, flutemazepam was the most rapid-acting compound of the series via oral administration, with noticeable sedative-hypnotic effects beginning 10-15 minutes post-ingestion. At equipotent doses, it was the most active and effective anxiolytic, myorelaxant, tranquilizer, sedative-hypnotic, and anti-convulsive agent at doses as low as 0.5–1 mg range. It had motor-impairing, amnesic, ataxia, and loss of balance as side effects (1–5%), the highest in the series.{{cite web |last1=Bingham |first1=EM |title=Process for the preparation of 3-fluorobenzodiazepines |url=https://patents.google.com/patent/US4120856A/en |website=Google Patents |publisher=US Patent US4120856A |access-date=30 July 2022}}