Cloxazolam

Cloxazolam

Systematic (IUPAC) name
13-chloro-2-(2-chlorophenyl)-3-oxa-6,9-diazatricyclo[8.4.0.02,6]tetradeca-1(10),11,13-trien-8-one
Clinical data
AHFS/Drugs.com	International Drug Names
Pregnancy cat.	?
Legal status	Schedule IV(US)
Routes	Oral
Pharmacokinetic data
Bioavailability	?
Metabolism	Hepatic
Half-life	65 Hours
Excretion	Renal
Identifiers
CAS number	24166-13-0 Y
ATC code	N05BA22
PubChem	CID 2816
DrugBank	DB01553
ChemSpider	2714 Y
UNII	GYL649Z0HY Y
KEGG	D01268 Y
Chemical data
Formula	C17H14Cl2N2O2
Mol. mass	349.2
SMILES	eMolecules & PubChem
InChI InChI=1S/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) Y Key:ZIXNZOBDFKSQTC-UHFFFAOYSA-N Y
Y(what is this?)  (verify)

Cloxazolam^[1] (marketed under brand name Sepazon, Olcadil (Brazil, Portugal and Spain), Akton (Belgium), Lubalix (Switzerland) is a drug which is a benzodiazepine derivative.^[2] Cloxazolam is metabolised into the active metabolite chlordesmethyldiazepam (delorazepam).^[3] It possesses anxiolytic,^[4] anticonvulsant,^[5] hypnotic,^[6] sedative^[7] and skeletal muscle relaxant properties.^[8]

Indications

Cloxazolam's main use is as an anti-anxiety drug.^[9]

Side effects

An increased heart rate may occur as an adverse effect of cloxazolam.^[10]

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.^[11]

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.^[12] However, because the parent prodrugs of cloxazolam and oxazolam were tested rather than the active metabolites, this is purely speculative.

See also

• Benzodiazepine

References

1. ^ DE Patent 1817923
2. ^ "Benzodiazepine Names". non-benzodiazepines.org.uk. http://www.non-benzodiazepines.org.uk/benzodiazepine-names.html. Retrieved 2008-12-29. 
3. ^ Oliveira-Silva, D.; Oliveira, CH.; Mendes, GD.; Galvinas, PA.; Barrientos-Astigarraga, RE.; De Nucci, G. (Dec 2009). "Quantification of chlordesmethyldiazepam by liquid chromatography-tandem mass spectrometry: application to a cloxazolam bioequivalence study.". Biomed Chromatogr 23 (12): 1266–75. doi:10.1002/bmc.1249. PMID 19488979. 
4. ^ Kamioka, T.; Nakayama, I.; Akiyama, S.; Takagi, H. (Mar 1977). "Effects of oxazolam, cloxazolam, and CS-386, new anti-anxiety drugs, on socially induced suppression and aggression in pairs of monkeys.". Psychopharmacology (Berl) 52 (1): 17–23. doi:10.1007/BF00426594. PMID 15296. 
5. ^ Ito, M.; Miyajima, T.; Fujii, T.; Okuno, T. (Feb 2004). "Cloxazolam treatment for patients with intractable epilepsy.". Pediatr Neurol 30 (2): 111–4. doi:10.1016/j.pediatrneurol.2003.07.004. PMID 14984903. 
6. ^ Inoue, H.; Maeno, Y.; Iwasa, M.; Matoba, R.; Nagao, M. (Sep 2000). "Screening and determination of benzodiazepines in whole blood using solid-phase extraction and gas chromatography/mass spectrometry.". Forensic Sci Int 113 (1–3): 367–73. doi:10.1016/S0379-0738(00)00226-7. PMID 10978650. 
7. ^ Brisse, B.; Tetsch, P.; Toye, A. (1980). "[Clinical study on stress protective action of cloxazolam in jaw surgery in double blind comparison to placebo (author's transl)]". Arzneimittelforschung 30 (4): 679–82. PMID 6104969. 
8. ^ Ansseau, M.; von Frenckell, R. (1990). "Controlled comparison of two anxiolytic benzodiazepines, cloxazolam and bromazepam". Neuropsychobiology 24 (1): 25–9. doi:10.1159/000119038. PMID 1983433. 
9. ^ Fischer-Cornelssen, KA. (1981). "Multicenter trials and complementary studies of cloxazolam, a new anxiolytic drug". Arzneimittelforschung 31 (10): 1757–65. PMID 6119092. 
10. ^ Boucsein, W.; Wendt-Suhl, G. (Mar 1982). "[Psychological and physiological effects of cloxazolam and diazepam under anxiety-evoking and control conditions on healthy subjects (author's transl)]". Pharmacopsychiatria 15 (2): 48–56. doi:10.1055/s-2007-1019508. PMID 6123123. 
11. ^ Nakatsuka, I.; Shimizu, H.; Asami, Y.; Katoh, T.; Hirose, A.; Yoshitake, A. (Jan 1985). "Benzodiazepines and their metabolites: relationship between binding affinity to the benzodiazepine receptor and pharmacological activity". Life Sci 36 (2): 113–9. doi:10.1016/0024-3205(85)90089-X. PMID 2857046. 
12. ^ Usami N; Yamamoto T, Shintani S, Ishikura S, Higaki Y, Katagiri Y, Hara A. (Apr 2002). "Substrate specificity of human 3(20)alpha-hydroxysteroid dehydrogenase for neurosteroids and its inhibition by benzodiazepines" (pdf). Biol Pharm Bull. 25 (4): 441–5. doi:10.1248/bpb.25.441. PMID 11995921. http://www.jstage.jst.go.jp/article/bpb/25/4/441/_pdf. 

External links

• Inchem.org - Cloxazolam