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Systematic (IUPAC) name
Clinical data
  •  ?
Routes of
Legal status
Legal status
Pharmacokinetic data
Bioavailability 90%
Protein binding 83%
Metabolism Hepatic
Biological half-life 18 hours
Excretion Renal
CAS Number 22316-47-8
ATC code N05BA09 (WHO)
PubChem CID 2789
DrugBank APRD00307
ChemSpider 2687
Chemical data
Formula C16H13ClN2O2
Molar mass 300.74[[Script error: No such module "String".]]
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Clobazam, (marketed under the brand names Frisium and Urbanol), is a drug which is a benzodiazepine derivative. It has been marketed as an anxiolytic since 1975[2] and an anticonvulsant since 1984.[3]


As of 2005, clobazam (Frisium) is approved in Canada for adjunctive use in tonic-clonic, complex partial, and myoclonic seizures.[4] Clobazam (Urbanyl[5]) is approved for adjunctive therapy in complex partial seizures[6] certain types of status epilepticus, specifically the myoclonic, myoclonic-absent, simple partial, complex partial, and tonic varieties,[7] and non-status absence seizures.[8] It is also approved for treatment of anxiety. In India, clobazam (Frisium, Aventis Pharma India, Ltd.) is approved for use as an adjunctive therapy in epilepsy and in acute and chronic anxiety.[9] In Japan, clobazam (Mystan[10]) is approved for adjunctive therapy in treatment-resistant epilepsy featuring complex partial seizures.[11] In New Zealand, clobazam is marketed as Frisium[12] In the United Kingdom clobazam (Frisium) is approved for short-term (2–4 weeks) relief of acute anxiety in patients who have not responded to other drugs, with or without insomnia and without uncontrolled clinical depression.[13]

It is also approved for adjunctive therapy for epilepsy in patients who have not responded to first-line drugs and in children who are refractory to first-line drugs. It is not recommended for use in children between the ages of six months and three years, unless there is a compelling need.[13] In addition to epilepsy and severe anxiety, clobazam is also approved as a short term (2–4 weeks) adjunctive agent in schizophrenia and other psychotic disorders to manage anxiety or agitation.[13]

Clobazam is sometimes used for refractory epilepsies. However, long-term prophylactic treatment of epilepsy has considerable drawbacks, most importantly loss of antiepileptic effects due to tolerance which may render long-term therapy ineffective.[14] Other antiepileptic drugs may therefore be preferred for the long term management of epilepsy. Furthermore, benzodiazepines have the drawback, particularly after long-term use, of causing rebound seizures upon abrupt or over-rapid discontinuation of therapy forming part of the benzodiazepine withdrawal syndrome.


Clobazam is available in oral form only, due to its insolubility in water.

Side effects




Clobazam should be used with great care in patients with the following disorders:

Special caution

Benzodiazepines require special precaution if used in the elderly, during pregnancy, in children, alcohol or drug-dependent individuals and individuals with comorbid psychiatric disorders.[17]

Tolerance and dependence

In humans tolerance to the anticonvulsant effects of clobazam frequently occurs[18] and withdrawal seizures can occur during abrupt or overrapid withdrawal.[19]

Clobazam as with other benzodiazepine drugs can lead to physical dependence, addiction and what is known as the benzodiazepine withdrawal syndrome. Withdrawal from clobazam or other benzodiazepines after regular use often leads to withdrawal symptoms which are similar to those seen during alcohol and barbiturate withdrawal. The higher the dose and the longer the drug is taken for, the greater the risk of experiencing unpleasant withdrawal symptoms. Withdrawal symptoms can however occur from standard dosages and also after short term use. Benzodiazepine treatment should be discontinued as soon as possible via a slow and gradual dose reduction regime.[20]


Clobazam is an anticonvulsant.[21] Clobazam is a 1,5-benzodiazepine, meaning that its diazepine ring has nitrogen atoms at the 1 and 5 positions (instead of the usual 1 and 4). Like other 1,5-benzodiazepines (e.g., arfendazam, lofendazam), it has less affinity for the ω1-allosteric binding site on the GABAA receptor compared to the 1,4-benzodiazepines. It has selective affinity for the ω2 site, where it has agonistic activity.[10]

In a double-blind placebo-controlled trial published in 1990 comparing it to clonazepam, 10 mg or 20 mg of clobazam was shown to be much less sedating than either 0.5 mg or 1 mg of clonazepam.[22]

The ω1-receptor, which is found on the α1 subtype of the GABAA receptor, was shown to be responsible for the sedative effects of diazepam by McKernan et al. in 2000, who also showed that its anxiolytic and anticonvulsant properties could still be seen in mice whose α1 receptors were insensitive to diazepam.[23] It would seem, then, that the anticonvulsant properties of clobazam are due to its selective affinity for ω2.

In 1996, Nakamura et al. reported that clobazam and its active metabolite, N-desmethylclobazam (norclobazam), work by enhancing GABA-activated chloride currents at GABAA-receptor-coupled Cl- channels. It was also reported that these effects were inhibited by the GABA antagonist flumazenil, and that clobazam acts most efficiently in GABA-deficient brain tissue.[24]


Clobazam has two major metabolites: N-desmethyl-clobazam and 4'-hydroxyclobazam, the former of which is active.[25] The demethylation is facilitated by CYP2C19, CYP3A4, and CYP2B6 and the 4'-hydroxyclobazam by CYP2C18 and CYP2C19.[26]

Drug Interactions


Benzodiazepines usually are not fatal when taken alone in overdose but those with underlying health conditions for example respiratory disease or when benzodiazepines are taken in combination with other CNS depressant drugs can result in death.[27]

Abuse potential

Clobazam in animal studies has been shown to increase reward seeking behaviours which may suggest an increased risk of addictive behavioural patterns.[28]


800px Weber, K. H.; Bauer, A.; Hauptmann, K. H.; Ann. 1972, 756, 128.

See also


  • Ochoa, Juan G. (2005). "GABA Receptor Agonists". Antiepileptic Drugs: An Overview., Inc. Retrieved 10 July 2005. 

End notes

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External links

fr:Clobazam it:Clobazam hu:Klobazám ja:クロバザム pl:Klobazam pt:Clobazam ru:Клобазам fi:Klobatsaami

  1. "MISUSE OF DRUGS ACT 1975". Retrieved 28 September 2005. 
  2. Freche, C. (1975). "[Study of an anxiolytic, clobazam, in otorhinolaryngology in psychosomatic pharyngeal manifestations]". Semaine des Hopitaux. Therapeutique. 51 (4): 261–3. PMID 5777.  [Article in French] [No abstract] List of Library Holdings Worldwide
  3. No authors listed (1991). "Clobazam in treatment of refractory epilepsy: the Canadian experience. A retrospective study. Canadian Clobazam Cooperative Group". Epilepsia. 32 (3): 407–16. doi:10.1111/j.1528-1157.1991.tb04670.x. PMID 2044502.  List of Library Holdings
  4. Epilepsy Ontario (2005). "Clobazam". Medications. Retrieved 2006-03-04. 
  5. "Liste des médicaments contenant la substance: Clobazam". Retrieved 2005-09-28.  Vidal.
  6. Larrieu JL, Lagueny A, Ferrer X, Julien J (1986). "[Epilepsy with continuous discharges during slow-wave sleep. Treatment with clobazam]". Revue d'Electroencephalographie et de Neurophysiologie Clinique. 16 (4): 383–94.  [Article in French] PMID 3103177 List of Library Holdings Worldwide
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  8. Biam Database (2001). "CLOBAZAM". Classes Chimiques: BENZODIAZEPINE. Retrieved 2005-09-28. 
  9. "Frisium Press Kit". Aventis Pharma India. Archived from the original on 2005-03-05. Retrieved 2006-08-02. 
  10. 10.0 10.1 Nakajima H (2001). "[A pharmacological profile of clobazam (Mystan), a new antiepileptic drug]" (PDF). Nippon Yakurigaku Zasshi. 118 (2): 117–22. PMID 11530681.  [Article in Japanese]
  11. Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found. List of Library Holdings Worldwide
  12. Epilepsy New Zealand (2000). "Antiepileptic Medication". Retrieved 11 July 2005. 
  13. 13.0 13.1 13.2 sanofi-aventis (2002). "Frisium Tablets 10 mg, Summary of Product Characteristics from eMC". electronic Medicines Compendium. Retrieved 11 July 2005. 
  14. Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found.
  15. Lua error in package.lua at line 80: module 'Module:Citation/CS1/Suggestions' not found. [Article in Japanese] PMID 13677950 List of Library Holdings Worldwide
  16. Monjanel-Mouterde S, Antoni M, Bun H, Botta-Frindlund D, Gauthier A, Durand A, Cano JP (1994). "Pharmacokinetics of a single oral dose of clobazam in patients with liver disease". Annual Review of Pharmacology and Toxicology. 74 (6): 345–50. PMID 7937568.  List of Library Holdings Worldwide
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  18. Loiseau P (1983). "[Benzodiazepines in the treatment of epilepsy]". Encephale. 9 (4 Suppl 2): 287B–292B. PMID 6373234. 
  19. Robertson MM (1986). "Current status of the 1,4- and 1,5-benzodiazepines in the treatment of epilepsy: the place of clobazam". Epilepsia. 27 Suppl 1: S27–41. doi:10.1111/j.1528-1157.1986.tb05730.x. PMID 3527689. 
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  22. Wildin JD, Pleuvry BJ, Mawer GE, Onon T, Millington L (1990). "Respiratory and sedative effects of clobazam and clonazepam in volunteers". British Journal of Clinical Pharmacology. 29 (2): 169–77. PMC 1380080Freely accessible. PMID 2106335. List of Library Holdings Worldwide
  23. McKernan RM, Rosahl TW, Reynolds DS, Sur C, Wafford KA, Atack JR, Farrar S, Myers J, Cook G, Ferris P, Garrett L, Bristow L, Marshall G, Macaulay A, Brown N, Howell O, Moore KW, Carling RW, Street LJ, Castro JL, Ragan CI, Dawson GR, Whiting PJ (2000). "Sedative but not anxiolytic properties of benzodiazepines are mediated by the GABA(A) receptor alpha1 subtype". Nature Neuroscience. 3 (6): 587–92. doi:10.1038/75761. PMID 10816315. 
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  25. Contin M, Sangiorgi S, Riva R, Parmeggiani A, Albani F, Baruzzi A (2002). "Evidence of polymorphic CYP2C19 involvement in the human metabolism of N-desmethylclobazam". Therapeutic Drug Monitoring. 24 (6): 737–41. doi:10.1097/00007691-200212000-00009. PMID 12451290.  List of Library Holdings Worldwide
  26. Giraud C, Tran A, Rey E, Vincent J, Treluyer JM, Pons G (2004). "In vitro characterization of clobazam metabolism by recombinant cytochrome P450 enzymes: importance of CYP2C19". Drug Metabolism and Disposition. 32 (11): 1279–86. doi:10.1124/dmd.32.11. Check |doi= value (help). PMID 15483195.  List of Library Holdings Worldwide
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