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Clinical data
Trade namesVeratran, Rize, Clozan
AHFS/Drugs.comInternational Drug Names
  • ?
Routes of
Oral, sublingual, liquid drops
ATC code
Legal status
Legal status
Pharmacokinetic data
Elimination half-life6-18 hr
CAS Number
PubChem CID
E number{{#property:P628}}
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Chemical and physical data
Molar mass318.8 g/mol
3D model (JSmol)
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]


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 The clotiazepam molecule differs from most other benzodiazepines in that the benzene ring has been replaced by a thiophene ring.[2] It possesses anxiolytic,[3] skeletal muscle relaxant,[4] anticonvulsant, sedative properties.[5] Stage 2 NREM sleep is significantly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]


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]


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]


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]


Clotiazepam is a recognised drug of abuse.[18]

See also


  1. DE Patent 2107356
  2. Niwa T, Shiraga T, Ishii I, Kagayama A, Takagi A; Shiraga; Ishii; Kagayama; Takagi (September 2005). "Contribution of human hepatic cytochrome p450 isoforms to the metabolism of psychotropic drugs" (PDF). Biol. Pharm. Bull. 28 (9): 1711–6. doi:10.1248/bpb.28.1711. PMID 16141545.
  3. Klicpera, C.; Strian, F. (May 1978). "Autonomic perception and responses in anxiety-inducing situations". Pharmakopsychiatr Neuropsychopharmakol. 11 (3): 113–20. doi:10.1055/s-0028-1094569. PMID 27828.
  4. Fukuda, T.; Tsumagari, T. (Aug 1983). "Effects of psychotropic drugs on the rage responses induced by electrical stimulation of the medial hypothalamus in cats" (PDF). Jpn J Pharmacol. 33 (4): 885–90. doi:10.1254/jjp.33.885. PMID 6632385.
  5. 5.0 5.1 Mandrioli, R.; Mercolini, L.; Raggi, MA. (Oct 2008). "Benzodiazepine metabolism: an analytical perspective". Curr Drug Metab. 9 (8): 827–44. doi:10.2174/138920008786049258. PMID 18855614.
  6. Nakazawa Y; Kotorii M; Oshima M; Horikawa S; Tachibana H. (October 31, 1975). "Effects of thienodiazepine derivatives on human sleep as compared to those of benzodiazepine derivatives". Psychopharmacologia. 44 (2): 165–71. doi:10.1007/BF00421005. PMID 709.
  7. Martucci, N.; Manna, V.; Agnoli, A. (Apr 1987). "A clinical and neurophysiological evaluation of clotiazepam, a new thienodiazepine derivative". Int Clin Psychopharmacol. 2 (2): 121–8. doi:10.1097/00004850-198704000-00005. PMID 2885366.
  8. Official Japanese Drug Information Sheet (Kusuri-no-Shiori)
  9. French Guide to Medicines - Clotiazepam (Veratran)
  10. C. Benvenuti, V. Bottà, M. Broggini, V. Gambaro, F. Lodi and M. Valenti (1989). "The pharmacokinetics of clotiazepam after oral and sublingual administration to volunteers". European Journal of Clinical Pharmacology. 37 (6): 617–619. doi:10.1007/BF00562556. PMID 2575522. Unknown parameter |doi_brokendate= ignored (help)
  11. Yakushiji, T.; Fukuda, T.; Oyama, Y.; Akaike, N. (Nov 1989). "Effects of benzodiazepines and non-benzodiazepine compounds on the GABA-induced response in frog isolated sensory neurones" (PDF). Br J Pharmacol. 98 (3): 735–40. doi:10.1111/j.1476-5381.1989.tb14600.x. PMC 1854765. PMID 2574062.
  12. Greenblatt, DJ.; Divoll, M.; Abernethy, DR.; Ochs, HR.; Shader, RI. (1983). "Clinical pharmacokinetics of the newer benzodiazepines". Clin Pharmacokinet. 8 (3): 233–52. doi:10.2165/00003088-198308030-00003. PMID 6133664.
  13. 13.0 13.1 Arendt, R.; Ochs, HR.; Greenblatt, DJ. (1982). "Electron capture GLC analysis of the thienodiazepine clotiazepam. Preliminary pharmacokinetic studies". Arzneimittelforschung. 32 (4): 453–5. PMID 6125154.
  14. Ochs, HR.; Greenblatt, DJ.; Verburg-Ochs, B.; Harmatz, JS.; Grehl, H. (1984). "Disposition of clotiazepam: influence of age, sex, oral contraceptives, cimetidine, isoniazid and ethanol". Eur J Clin Pharmacol. 26 (1): 55–9. doi:10.1007/BF00546709. PMID 6143670.
  15. Ochs, HR.; Greenblatt, DJ.; Knüchel, M. (1986). "Effect of cirrhosis and renal failure on the kinetics of clotiazepam". Eur J Clin Pharmacol. 30 (1): 89–92. doi:10.1007/BF00614202. PMID 2872061.
  16. Colonna, L.; Cozzi, F.; Del Citerna, F.; Di Benedetto, A.; De Divitiis, O.; Furlanello, F.; Milazzotto, F.; Pittalis, M.; Taccola, A. (1990). "[Multicenter study of the effectiveness and tolerance of clotiazepam in cardiology]". Minerva Cardioangiol. 38 (1–2): 45–9. PMID 1971433.
  17. Habersetzer, F.; Larrey, D.; Babany, G.; Degott, C.; Corbic, M.; Pessayre, D.; Benhamou, JP. (Sep 1989). "Clotiazepam-induced acute hepatitis". J Hepatol. 9 (2): 256–9. doi:10.1016/0168-8278(89)90060-3. PMID 2572625.
  18. Shimamine, M.; Masunari, T.; Nakahara, Y. (1993). "[Studies on identification of drugs of abuse by diode array detection. I. Screening-test and identification of benzodiazepines by HPLC-DAD with ICOS software system]". Eisei Shikenjo Hokoku (111): 47–56. PMID 7920567.

External links

Template:Benzodiazepines Template:Anxiolytics Template:GABAAR PAMs