Cloxazolam: Difference between revisions

| verifiedrevid = 448830245

| IUPAC_name = 13-chloro-2-(2-chlorophenyl)-3-oxa-6,9-diazatricyclo[8.4.0.0^2,6]tetradeca-1(10),11,13-trien-8-one

| image = Cloxazolam structure.svg

| width = 134

| image2 = Cloxazolam3d.png

| tradename =

| pregnancy_category = ?

| legal_status = [[Schedule IV controlled substance|Schedule IV]](US)

| bioavailability = ?

| elimination_half-life = 65 Hours

| molecular_weight = 349.2

| InChI = 1/C17H14Cl2N2O2/c18-11-5-6-15-13(9-11)17(12-3-1-2-4-14(12)19)21(7-8-23-17)10-16(22)20-15/h1-6,9H,7-8,10H2,(H,20,22)

| InChIKey = ZIXNZOBDFKSQTC-UHFFFAOYAN

'''Cloxazolam''' (marketed under brand name '''Sepazon''', '''Olcadil''' (Brazil, Portugal and Spain), '''Akton''' (Belgium), '''Lubalix''' (Switzerland) is a drug which is a [[benzodiazepine]] derivative.<ref>{{cite web| url= http://www.non-benzodiazepines.org.uk/benzodiazepine-names.html| title=Benzodiazepine Names| accessdate=2008-12-29| publisher=non-benzodiazepines.org.uk}}</ref> Cloxazolam is metabolised into the [[active metabolite]] [[chlordesmethyldiazepam]] (delorazepam).<ref>{{Cite journal | last1 = Oliveira-Silva | first1 = D. | last2 = Oliveira | first2 = CH. | last3 = Mendes | first3 = GD. | last4 = Galvinas | first4 = PA. | last5 = Barrientos-Astigarraga | first5 = RE. | last6 = De Nucci | first6 = G. | title = Quantification of chlordesmethyldiazepam by liquid chromatography-tandem mass spectrometry: application to a cloxazolam bioequivalence study. | journal = Biomed Chromatogr | volume = 23 | issue = 12 | pages = 1266–75 | month = Dec | year = 2009 | doi = 10.1002/bmc.1249 | pmid = 19488979 }}</ref> It possesses [[anxiolytic]],<ref>{{Cite journal | last1 = Kamioka | first1 = T. | last2 = Nakayama | first2 = I. | last3 = Akiyama | first3 = S. | last4 = Takagi | first4 = H. | title = Effects of oxazolam, cloxazolam, and CS-386, new anti-anxiety drugs, on socially induced suppression and aggression in pairs of monkeys. | journal = Psychopharmacology (Berl) | volume = 52 | issue = 1 | pages = 17–23 | month = Mar | year = 1977 | doi = 10.1007/BF00426594| pmid = 15296 }}</ref> [[anticonvulsant]],<ref>{{Cite journal | last1 = Ito | first1 = M. | last2 = Miyajima | first2 = T. | last3 = Fujii | first3 = T. | last4 = Okuno | first4 = T. | title = Cloxazolam treatment for patients with intractable epilepsy. | journal = Pediatr Neurol | volume = 30 | issue = 2 | pages = 111–4 | month = Feb | year = 2004 | doi = 10.1016/j.pediatrneurol.2003.07.004 | pmid = 14984903 }}</ref> [[hypnotic]],<ref>{{Cite journal | last1 = Inoue | first1 = H. | last2 = Maeno | first2 = Y. | last3 = Iwasa | first3 = M. | last4 = Matoba | first4 = R. | last5 = Nagao | first5 = M. | title = Screening and determination of benzodiazepines in whole blood using solid-phase extraction and gas chromatography/mass spectrometry. | journal = Forensic Sci Int | volume = 113 | issue = 1–3 | pages = 367–73 | month = Sep | year = 2000 | doi = 10.1016/S0379-0738(00)00226-7| pmid = 10978650 }}</ref> [[sedative]]<ref>{{Cite journal | last1 = Brisse | first1 = B. | last2 = Tetsch | first2 = P. | last3 = Toye | first3 = A. | title = [Clinical study on stress protective action of cloxazolam in jaw surgery in double blind comparison to placebo (author's transl)] | journal = Arzneimittelforschung | volume = 30 | issue = 4 | pages = 679–82 | month = | year = 1980 | doi = | pmid = 6104969 }}</ref> and [[skeletal muscle relaxant]] properties.<ref>{{Cite journal | last1 = Ansseau | first1 = M. | last2 = von Frenckell | first2 = R. | title = Controlled comparison of two anxiolytic benzodiazepines, cloxazolam and bromazepam | journal = Neuropsychobiology | volume = 24 | issue = 1 | pages = 25–9 | month = | year = 1990| doi = 10.1159/000119038| pmid = 1983433 }}</ref>

==Indications==

Cloxazolam's main use is as an anti-anxiety drug.<ref>{{Cite journal | last1 = Fischer-Cornelssen | first1 = KA. | title = Multicenter trials and complementary studies of cloxazolam, a new anxiolytic drug | journal = Arzneimittelforschung | volume = 31 | issue = 10 | pages = 1757–65 | month = | year = 1981 | pmid = 6119092 }}</ref>

==Side effects==

An increased heart rate may occur as an adverse effect of cloxazolam.<ref>{{Cite journal | last1 = Boucsein | first1 = W. | last2 = Wendt-Suhl | first2 = G. | title = [Psychological and physiological effects of cloxazolam and diazepam under anxiety-evoking and control conditions on healthy subjects (author's transl)] | journal = Pharmacopsychiatria | volume = 15 | issue = 2 | pages = 48–56 | month = Mar | year = 1982 | doi = 10.1055/s-2007-1019508| pmid = 6123123 }}</ref>

==Pharmacology==

The pharmacological effects of cloxazolam are a result of mainly its [[active metabolites]], thus cloxazolam is a [[prodrug]]. The main site of action of cloxazolam and its active metabolites are the [[benzodiazepine receptor]].<ref>{{Cite journal | last1 = Nakatsuka | first1 = I. | last2 = Shimizu | first2 = H. | last3 = Asami | first3 = Y. | last4 = Katoh | first4 = T. | last5 = Hirose | first5 = A. | last6 = Yoshitake | first6 = A. | title = Benzodiazepines and their metabolites: relationship between binding affinity to the benzodiazepine receptor and pharmacological activity | journal = Life Sci | volume = 36 | issue = 2 | pages = 113–9 | month = Jan | year = 1985 | pmid = 2857046 | doi = 10.1016/0024-3205(85)90089-X }}</ref>

The [[pharmacological]] actions of benzodiazepines at the [[GABAa receptor]] are similar to those of [[neurosteroids]]. [[Neuroactive]] steroids are positive [[allosteric]] modulators of the GABAa receptor, enhancing [[GABA]] function and in turn have effects on mood and other functions. Many benzodiazepines ([[diazepam]], [[medazepam]], [[estazolam]], [[temazepam]], [[flunitrazepam]] and nitrazepam) potently inhibit the [[enzymes]] involved in the [[metabolism]] of neurosteroids. The tetrahydroxazole ring that cloxazolam and [[oxazolam]] have decreases the [[inhibitory]] potency of benzodiazepines on neurosteroids. Thus there could be subtle differences between cloxazolam and other benzodiazepines.<ref>{{cite journal | author = Usami N | coauthors = Yamamoto T, Shintani S, Ishikura S, Higaki Y, Katagiri Y, Hara A. | year = 2002 | month = Apr | title = Substrate specificity of human 3(20)alpha-hydroxysteroid dehydrogenase for neurosteroids and its inhibition by benzodiazepines | journal = Biol Pharm Bull. | volume = 25 | issue = 4 | pages = 441–5 | pmid = 11995921 | url = http://www.jstage.jst.go.jp/article/bpb/25/4/441/_pdf | format = pdf | doi = 10.1248/bpb.25.441 }}</ref> However, because the parent prodrugs of cloxazolam and oxazolam were tested rather than the active metabolites, this is purely speculative.

*[[Benzodiazepine]]

{{Reflist}}

{{Anxiolytics}}

[[Category:Hypnotics]]

[[Category:Organochlorides]]

[[Category:Lactams]]

[[ja:クロキサゾラム]]

[[pt:Cloxazolam]]

[[sv:Kloxazolam]]