Clotiazepam

From Infogalactic: the planetary knowledge core
Jump to: navigation, search
Clotiazepam
Clotiazepam structure.svg
Clotiazepam3d.png
Systematic (IUPAC) name
5-(2-chlorophenyl)-7-ethyl-1-methyl-3H-thieno[2,3-e][1,4]diazepin-2-one
Clinical data
Trade names Veratran, Rize, Clozan
AHFS/Drugs.com International Drug Names
Legal status
Routes of
administration		 Oral, sublingual, liquid drops
Pharmacokinetic data
Bioavailability ~90%
Metabolism Hepatic
Biological half-life 6–18 hours
Excretion Renal
Identifiers
CAS Number 33671-46-4 YesY
ATC code N05BA21 (WHO)
PubChem CID: 2811
DrugBank DB01559 YesY
ChemSpider 2709 YesY
UNII ZCN055599V YesY
KEGG D01328 YesY
ChEMBL CHEMBL1697737 N
Chemical data
Formula C16H15ClN2OS
Molecular mass 318.8 g/mol
  • ClC1=C(C2=NCC(N(C)C3=C2C=C(CC)S3)=O)C=CC=C1
  • InChI=1S/C16H15ClN2OS/c1-3-10-8-12-15(11-6-4-5-7-13(11)17)18-9-14(20)19(2)16(12)21-10/h4-8H,3,9H2,1-2H3 YesY
  • Key:CHBRHODLKOZEPZ-UHFFFAOYSA-N YesY
 NYesY (what is this?)  (verify)

Clotiazepam[1] (marketed under brand name Clozan, Distensan, Trecalmo, Rize, Rizen and Veratran) is a thienodiazepine drug which is a benzodiazepine analog. The clotiazepam molecule differs from most other benzodiazepines in that the benzene ring has been replaced by a thiophene ring.[2] It possesses anxiolytic,[3] skeletal muscle relaxant,[4] anticonvulsant, sedative properties.[5] Stage 2 NREM sleep is significantly increased by clotiazepam.[6]

Indications

Clotiazepam has been trialed and found to be effective in the short-term management of anxiety.[7] Clotiazepam is also used as a premedicant in minor surgery in France and Japan, where the drug is commercially available under the brand names Veratran and Rize, respectively.[8][9]

Pharmacokinetics

A cross-over study in six healthy volunteers (median age 28 years) was conducted using single-dose pharmacokinetics of 5 mg clotiazepam drops, oral tablets, and sublingual tablets. The formulations had similar systemic availability. Compared with oral tablets, the sublingual route gave a lower peak concentration and a delayed peak time, while drops gave a greater maximum concentration with a similar peak time. The use of drops is suggested for a more marked initial effect and the sublingual route for easier administration, especially in the elderly.[10]

Pharmacology

Similar to other benzodiazepines clotiazepam has anxiolytic, sedative, hypnotic, amnesic, anticonvulsant and muscle relaxant pharmacological properties.[5] Clotiazepam binds to the benzodiazepine site of the GABAA receptor where it acts as a full agonist; this action results in an enhanced GABA inhibitory effect at the GABAA receptor which results in the pharmacological effects of clotiazepam.[11]

Clotiazepam has a relatively short elimination half-life and is less prone to accumulation after repeated dosing compared to longer-acting benzodiazepine agents. It is metabolised via oxidation.[12] Clotiazepam is metabolised to hydroxy-clotiazepam and desmethyl-clotiazepam. After oral ingestion of a single 5 mg dose of clotiazepam by three healthy volunteers the drug was rapidly absorbed.[13] The elimination half-life of the drug and its metabolites range from 6.5 hours to 18 hours. Clotiazepam is 99 percent bound to plasma protein.[13] In elderly men the elimination half-life is longer and in elderly women the volume of distribution is increased.[14] Individuals with liver impairment have a reduced volume of distribution as well as a reduced total clearance of clotiazepam; renal impairment does not affect the kinetics of clotiazepam.[15]

Side effects

Drowsiness and asthenia are common side effects.[16] There has been a report of hepatitis caused by clotiazepam.[17]

Abuse

Clotiazepam is a recognised drug of abuse.[18]

See also

References

  1. ↑ DE Patent 2107356
  2. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  3. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  4. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  5. ↑ 5.0 5.1 Lua error in package.lua at line 80: module 'strict' not found.
  6. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  7. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  8. ↑ Official Japanese Drug Information Sheet (Kusuri-no-Shiori)
  9. ↑ French Guide to Medicines - Clotiazepam (Veratran)
  10. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  11. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  12. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  13. ↑ 13.0 13.1 Lua error in package.lua at line 80: module 'strict' not found.
  14. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  15. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  16. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  17. ↑ Lua error in package.lua at line 80: module 'strict' not found.
  18. ↑ Lua error in package.lua at line 80: module 'strict' not found.

External links

Retrieved from "https://infogalactic.com/w/index.php?title=Clotiazepam&oldid=4065796"