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Systematic (IUPAC) name
CAS number 22316-47-8
ATC code N05BA09
PubChem 2789
DrugBank APRD00307
Chemical data
Formula C16H13ClN2O2 
Mol. mass 300.74
Pharmacokinetic data
Bioavailability 90%
Metabolism Hepatic
Half life 18 hours
Excretion Renal
Therapeutic considerations
Pregnancy cat.


Legal status

Schedule IV (US)
Class C (New Zealand)[1]
Class C/Sch.4 (UK)

Routes Oral

Clobazam is a drug which is a benzodiazepine derivative. It has been marketed as an anxiolytic since 1975[2] and an anticonvulsant since 1984.[3]



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 (arfendazam, lofendazam, e.g.), 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.[4]

In a double-blind placebo-controlled trial published in 1990 comparing it to clonazepam, 10mg or 20 mg of clobazam was shown to be much less sedating than either 0.5mg or 1 mg of clonazepam.[5]

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.[6] 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.[7]

Nine years earlier, Kilpatrick et al noted that there was a correlation between plasma levels of norclobazam and therapeutic effects, although this was not true with the parent compound.[8]

According to Valli and colleagues in 1984, clobazam lowered prolactin levels elevated by sulpiride, a typical antipsychotic[9]. Hyperprolactinemia (i.e. elevated blood prolactin) occurs occasionally in people using antipsychotics, (particularly the typical ones), and can lead to cardiovascular disease, breast cancer, galactorrhea, infertility, amenorrhea, dysmenorrhea, osteopenia, osteoporosis, loss of libido, impotence,[10] and hypogonadism.[11]

Antipsychotics block type 2 dopamine receptors and at least 65% of central D2 receptors need to be occupied to produce a response; >72% D2 receptor occupancy was found to be associated with development of hyperprolactinemia.[12]

Peak plasma protein binding occurs around 83%.


Clobazam has two major metabolites: N-desmethyl-clobazam and 4'-hydroxyclobazam, the former of which is active.[13] The demethylation is facilitated by CYP2C19, CYP3A4, and CYP2B6 and the 4'-hydroxyclobazam by CYP2C18 and CYP2C19.[14]


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.[15]


As of 2005, clobazam (Frisium®) is approved in Canada for adjunctive use in tonic-clonic, complex partial, and myoclonic seizures.[16] Clobazam (Urbanyl®[17]) is approved for adjunctive therapy in complex partial seizures[18] certain types of status epilepticus, specifically the myoclonic, myoclonic-absent, simple partial, complex partial, and tonic varieties[19], and non-status absence seizures.[20] 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.[21] In Japan, clobazam (Mystan®[4]) is approved for adjunctive therapy in treatment-resistant epilepsy featuring complex partial seizures.[22] In New Zealand, clobazam is marketed as Frisium®[23] In the United Kingdom, clobazam (Frisium®) is approved in the United Kingdom 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.[24]

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.[24]

In addition to epilepsy and severe anxiety, clobazam is also approved as an adjunctive agent in schizophrenia and other psychotic disorders.[24]

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 useless.[25] Other antiepileptic drugs may therefore be preferred for the long term management of epielpsy. Also benzodiazepines have the draw back 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


  • Ataxia
  • Somnolence
  • Diplopia
  • Dysarthria


  • Gelastic seizures[26]
  • Urticaria
  • Rashes


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

  • Myasthenia gravis
  • Sleep apnea
  • Severe liver diseases such as cirrhosis and hepatitis[27]
  • Respiratory problems, including hypoventilation

Drug Interactions

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]


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

End Notes

  1. ^ MISUSE OF DRUGS ACT 1975. Retrieved on 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. PubMed. [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. PMID 2044502. List of Library Holdings
  4. ^ a b Nakajima H (2001). "[A pharmacological profile of clobazam (Mystan), a new antiepileptic drug]" (PDF). Nippon Yakurigaku Zasshi 118 (2): 117-22. PubMed. [Article in Japanese]
  5. ^ 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. PubMed.List of Library Holdings Worldwide
  6. ^ 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. PubMed.
  7. ^ Nakamura, Fumihiro; Suzuki Setsuo, Nishimura Shigeko, Yagi Kazuichi, and Seino Masakazu (1996). "Effects of clobazam and its active metabolite on GABA-activated currents in rat cerebral neurons in culture" (PDF). Epilepsia 37 (8): 728-35. PubMed. Retrieved on 2006-08-03.
  8. ^ Kilpatrick C, Bury R, Fullinfaw R, Moulds R (1987). "Clobazam in the treatment of epilepsy". Clinical and Experimental Neurology 23 (1): 139-44. PMID 3117456. List of Library Holdings Worldwide
  9. ^ Valli M, Courtiere A, Tamalet C, Jadot G (1984). "[Activity of clobazam on plasma prolactin and gonadotropins after administration of sulpiride in the male rat]". Annales d'Endocrinologie 45 (6): 409-11. [Article in French] PMID 6152598 List of Library Holdings Worldwide
  10. ^ Halbreich, Uriel; Linda S. Kahn (September 2003). "Hyperprolactinemia and Schizophrenia: Mechanisms and Clinical Aspects.". Journal of Psychiatric Practice 9 (5): 344-53. PMID 15985953.
  11. ^ Meaney, Anna Maria; Shubulade Smith, O. D. Howes, Moira O’Brien, Robin M. Murray, and Veronica O’Keane (June 2004). "Effects of long-term prolactin-raising antipsychotic medication on bone mineral density in patients with schizophrenia.". British Journal of Psychiatry 184: 503-508. PMID 15172944.
  12. ^ Kapur, Shitij; Robert Zipursky, Corey Jones, Gary Remington, and Sylvain Houle (April 2000). "Relationship Between Dopamine D2 Occupancy, Clinical Response, and Side Effects: A Double-Blind PET Study of First-Episode Schizophrenia". The American Journal of Psychiatry 157 (4): 514-20. PMID 10739409.
  13. ^ 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. PubMed. List of Library Holdings Worldwide
  14. ^ 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. PubMed. List of Library Holdings Worldwide
  15. ^ MacKinnon GL; Parker WA. (1982). "Benzodiazepine withdrawal syndrome: a literature review and evaluation.". The American journal of drug and alcohol abuse. 9 (1): 19-33. PMID 6133446.
  16. ^ Epilepsy Ontario (2005). Clobazam. Medications. Retrieved on 2006-03-04.
  17. ^ Liste des médicaments contenant la substance : Clobazam. Retrieved on 2005-09-28. Vidal.
  18. ^ 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
  19. ^ Gastaut, Henri; Tinuper P, Aguglia U, Lugaresi E (1984). "[Treatment of certain forms of status epilepticus by means of a single oral dose of clobazam]". Revue d'Electroencephalographie et de Neurophysiologie Clinique 14 (3): 203-6. PubMed.
  20. ^ Biam Database (2001). CLOBAZAM. Classes Chimiques: BENZODIAZEPINE. Retrieved on 2005-09-28.
  21. ^ Frisium Press Kit. Aventis Pharma India. Archived from the original on 2005-03-05. Retrieved on 2006-08-02.
  22. ^ Shimizu, Hisako; Kawasaki Jun, Yuasa Shoji, Tarao Yoko, Kumagai Sachiyo, Kanemoto Kousuke (2003). "Use of clobazam for the treatment of refractory complex partial seizures". Seizure 12 (5): 282-6. PubMed. List of Library Holdings Worldwide
  23. ^ Epilepsy New Zealand (2000). Antiepileptic Medication. Retrieved on 11 July, 2005.
  24. ^ a b c sanofi-aventis (2002). Frisium Tablets 10 mg, Summary of Product Characteristics from eMC. electronic Medicines Compendium. Retrieved on 11 July, 2005.
  25. ^ Isojärvi, JI; Tokola RA. (Dec 1998). "Benzodiazepines in the treatment of epilepsy in people with intellectual disability.". J Intellect Disabil Res. 42 (1): 80-92. PMID 10030438.
  26. ^ Iwasaki T; Miura H, Sunaoshi W, Hosoda N, Takei K, Katayama F (2003). "[A case of intractable epilepsy showing frequent gelastic seizures by administration of clobazam]". No To Hattatsu 35 (5): 406-10. [Article in Japanese] PMID 13677950 List of Library Holdings Worldwide
  27. ^ 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
  28. ^ Thiébot MH; Le Bihan C, Soubrié P, Simon P. (1985). "Benzodiazepines reduce the tolerance to reward delay in rats.". Psychopharmacology (Berl). 86 (1-2): 147-52. PMID 2862657.
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article "Clobazam". A list of authors is available in Wikipedia.
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