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Chemical Compound Review

Clobazam     10-chloro-6-methyl-2-phenyl- 2,6...

Synonyms: Clorepin, Noiafren, Chlorepin, Frisium, Urbadan, ...
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Disease relevance of Clorepin


Psychiatry related information on Clorepin

  • Results of studies of vigilance and psychomotor performance during therapeutic use in patients are less conclusive, but clobazam may be useful in anxious patients who experience such impairment with other benzodiazepines [6].
  • Although subjective drowsiness has occurred with similar frequency with clobazam and diazepam in some studies, clobazam causes less objectively measured sedation or psychomotor impairment in experimental studies [6].
  • On all five performance assessments (choice reaction times, serial subtraction times, critical flicker fusion values), there was a consistent tendancy for clobazam performance to be comparatively better under high stress, and for placebo performance to be comparatively better under low stress [7].
  • Except for clobazam by the maximal electroshock seizure (MES) test in rats, clobazam and valproate are effective in nontoxic doses against MES and all four chemically induced seizures (Metrazol, bicuculline, picrotoxin, and strychnine) [8].
  • 3 The advantage of clobazam compared with the 1.4 benzodiazepines lies mainly in the fact that motor activity is influenced only after very high doses, these doses being markedly above those required to induce tranquillizing and anti-agression activities [9].

High impact information on Clorepin

  • BACKGROUND: Stiripentol is an inhibitor of cytochrome P450 that showed antiepileptic efficacy in severe myoclonic epilepsy in infancy (SMEI) in association with clobazam and valproate in an open study [10].
  • A double-blind comparison of buspirone, clobazam, and placebo in patients with anxiety treated in a general practice setting [11].
  • The single-dose pharmacokinetic profile of clobazam is highly predictive of drug behaviour during repeated dosage, suggesting that clobazam kinetics are dose- and concentration-independent within the range studied, and that self-induction or inhibition of clearance is not evident during 3 weeks of dosage [12].
  • RESULTS: The mean (+/-standard deviation) urine 15-F(2t)-IsoP levels (nmol/mmol Cr) were: valproic acid (0.36 +/- 0.15); carbamazepine (0.24 +/- 0.10); clobazam (0.23 +/- 0.10); control group (0.20 +/- 0.09) [13].
  • PURPOSE: To confirm the efficacy and to clarify the problems of clobazam (CLB) as a new antiepileptic drug (AED) and clorazepate (CLP) as an alternative AED in Japan. METHODS: CLB and CLP were added on or replaced with conventional AEDs in 55 and 170 patients with refractory epilepsies, respectively [14].

Chemical compound and disease context of Clorepin


Biological context of Clorepin

  • Clobazam was administered in 13 patients; 15.4% of them were completely unresponsive, 23.1% experienced drug resistance, and 61.5% obtained a good control (91.5% reduction of the reflex seizures) for a mean of 22.75 months [20].
  • Clobazam, 20 or 30 mg/day was given for 10 days around menstruation in successive menstrual cycles to 13 women who had responded favourably to this drug in an earlier short-term placebo controlled cross-over study [21].
  • The effect of the new 1,5-benzodiazepine clobazam on visual evoked potentials (VEP) and spontaneous EEG in the conscious rabbit and on spinal polysynaptic reflexes in the decerebrated cat was studied in comparison to the 1,4-benzodiazepine diazepam [22].
  • The pharmacokinetics of clobazam were studied in six healthy volunteers and six age and sex matched enzyme-induced epileptic patients [23].
  • The increase in AUC for NDMC generated from clobazam was also relatively greater than that for NDMC administered orally [24].

Anatomical context of Clorepin


Associations of Clorepin with other chemical compounds


Gene context of Clorepin


Analytical, diagnostic and therapeutic context of Clorepin


  1. Phenytoin toxicity due to interaction with clobazam. Zifkin, B., Sherwin, A., Andermann, F. Neurology (1991) [Pubmed]
  2. Paroxysmal language disturbance in an epileptic treated with clobazam. Wilson, A., Petty, R., Perry, A., Rose, F.C. Neurology (1983) [Pubmed]
  3. Use of clobazam in certain forms of status epilepticus and in startle-induced epileptic seizures. Tinuper, P., Aguglia, U., Gastaut, H. Epilepsia (1986) [Pubmed]
  4. Tolerance to the anticonvulsant effects of clobazam in mice. Wildin, J.D., Pleuvry, B.J. Neuropharmacology (1992) [Pubmed]
  5. Carbamazepine intoxication with negative myoclonus after the addition of clobazam. Genton, P., Nguyen, V.H., Mesdjian, E. Epilepsia (1998) [Pubmed]
  6. Clobazam: a review of its pharmacological properties and therapeutic use in anxiety. Brogden, R.N., Heel, R.C., Speight, T.M., Avery, G.S. Drugs (1980) [Pubmed]
  7. Effects of a 1,5-benzodiazepine derivative upon performance in an experimental stress situation. Parrott, A.C., Davies, S. Psychopharmacology (Berl.) (1983) [Pubmed]
  8. Comparative anticonvulsant activity and neurotoxicity of clobazam, diazepam, phenobarbital, and valproate in mice and rats. Shenoy, A.K., Miyahara, J.T., Swinyard, E.A., Kupferberg, H.J. Epilepsia (1982) [Pubmed]
  9. Pharmacology of anti-anxiety drugs with special reference to clobazam. Fielding, S., Hoffmann, I. British journal of clinical pharmacology. (1979) [Pubmed]
  10. Stiripentol in severe myoclonic epilepsy in infancy: a randomised placebo-controlled syndrome-dedicated trial. STICLO study group. Chiron, C., Marchand, M.C., Tran, A., Rey, E., d'Athis, P., Vincent, J., Dulac, O., Pons, G. Lancet (2000) [Pubmed]
  11. A double-blind comparison of buspirone, clobazam, and placebo in patients with anxiety treated in a general practice setting. Böhm, C., Placchi, M., Stallone, F., Gammans, R.E., Alms, D.R., Shrotriya, R.C., Robinson, D.S. Journal of clinical psychopharmacology. (1990) [Pubmed]
  12. Reduced single-dose clearance of clobazam in elderly men predicts increased multiple-dose accumulation. Greenblatt, D.J., Divoll, M., Puri, S.K., Ho, I., Zinny, M.A., Shader, R.I. Clinical pharmacokinetics. (1983) [Pubmed]
  13. Oxidative stress in children receiving valproic acid. Michoulas, A., Tong, V., Teng, X.W., Chang, T.K., Abbott, F.S., Farrell, K. J. Pediatr. (2006) [Pubmed]
  14. Clobazam as a new antiepileptic drug and clorazepate dipotassium as an alternative antiepileptic drug in Japan. Sugai, K. Epilepsia (2004) [Pubmed]
  15. Clobazam: uncontrolled and standard controlled clinical trials. Ban, T.A., Amin, M.M. British journal of clinical pharmacology. (1979) [Pubmed]
  16. The effects of clobazam and lorazepam on aspects of psychomotor performance and car handling ability. Hindmarch, I., Gudgeon, A.C. British journal of clinical pharmacology. (1980) [Pubmed]
  17. Pharmacodynamic effects of buspirone and clobazam. Alford, C., Bhatti, J.Z., Curran, S., McKay, G., Hindmarch, I. British journal of clinical pharmacology. (1991) [Pubmed]
  18. Some aspects of the effects of clobazam on human psychomotor performance. Hindmarch, I. British journal of clinical pharmacology. (1979) [Pubmed]
  19. Effect of the 1,5-benzodiazepines, clobazam and triflubazam, on sleep in man. Nicholson, A.N., Stone, B.M., Clarke, C.H. British journal of clinical pharmacology. (1977) [Pubmed]
  20. Startle-induced epileptic seizures. Aguglia, U., Tinuper, P., Gastaut, H. Epilepsia (1984) [Pubmed]
  21. Intermittent clobazam for catamenial epilepsy: tolerance avoided. Feely, M., Gibson, J. J. Neurol. Neurosurg. Psychiatr. (1984) [Pubmed]
  22. Neuropharmacological profile of clobazam, a new 1',5'-benzodiazepine. Gerhards, H.J. Psychopharmacology (Berl.) (1978) [Pubmed]
  23. Single dose pharmacokinetic study of clobazam in normal volunteers and epileptic patients. Jawad, S., Richens, A., Oxley, J. British journal of clinical pharmacology. (1984) [Pubmed]
  24. The effect of cimetidine on the single dose pharmacokinetics of oral clobazam and N-desmethylclobazam. Pullar, T., Edwards, D., Haigh, J.R., Peaker, S., Feely, M.P. British journal of clinical pharmacology. (1987) [Pubmed]
  25. Development of tolerance to clobazam in fully kindled rats: effects of intermittent flumazenil administration. Löscher, W., Rundfeldt, C. Eur. J. Pharmacol. (1990) [Pubmed]
  26. Neuroethological evaluation of audiogenic seizures and audiogenic-like seizures induced by microinjection of bicuculline into the inferior colliculus. II. Effects of nigral clobazam microinjections. Terra, V.C., Garcia-Cairasco, N. Behav. Brain Res. (1992) [Pubmed]
  27. Antagonism by antidepressant drugs of the inhibitory effect of trifluoromethylphenylpiperazine (TFMPP) on [3H]acetylcholine release in rat or guinea-pig hippocampal synaptosomes. Harel-Dupas, C., Cloëz, I., Fillion, G. European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology. (1991) [Pubmed]
  28. Evaluation of native GABA(A) receptors containing an alpha 5 subunit. Li, M., Szabo, A., Rosenberg, H.C. Eur. J. Pharmacol. (2001) [Pubmed]
  29. Guidelines for the rational use of benzodiazepines. When and what to use. Ashton, H. Drugs (1994) [Pubmed]
  30. Status epilepticus in benign rolandic epilepsy manifesting as anterior operculum syndrome. Colamaria, V., Sgrò, V., Caraballo, R., Simeone, M., Zullini, E., Fontana, E., Zanetti, R., Grimau-Merino, R., Dalla Bernardina, B. Epilepsia (1991) [Pubmed]
  31. Pharmacokinetics of N-desmethylclobazam in healthy volunteers and patients with epilepsy. Pullar, T., Haigh, J.R., Peaker, S., Feely, M.P. British journal of clinical pharmacology. (1987) [Pubmed]
  32. Evaluation of the effects of clobazam, A 1,5 benzodiazepine, on mood and psychomotor performance in clinically anxious patients in general practice. Salkind, M.R., Hanks, G.W., Silverstone, J.T. British journal of clinical pharmacology. (1979) [Pubmed]
  33. Simple and sensitive method for the determination of clobazam, clonazepam and nitrazepam in human serum by high-performance liquid chromatography. Zilli, M.A., Nisi, G. J. Chromatogr. (1986) [Pubmed]
  34. In vitro characterization of clobazam metabolism by recombinant cytochrome P450 enzymes: importance of CYP2C19. Giraud, C., Tran, A., Rey, E., Vincent, J., Tréluyer, J.M., Pons, G. Drug Metab. Dispos. (2004) [Pubmed]
  35. Clobazam for epilepsy. Reynolds, E.H., Heller, A.J., Ring, H.A. Lancet (1988) [Pubmed]
  36. Anticonvulsant action of a 1,5-benzodiazepine, clobazam, in reflex epilepsy. Chapman, A.G., Horton, R.W., Meldrum, B.S. Epilepsia (1978) [Pubmed]
  37. Forensic intoxication with clobazam: HPLC/DAD/MSD analysis. Proença, P., Teixeira, H., Pinheiro, J., Marques, E.P., Vieira, D.N. Forensic Sci. Int. (2004) [Pubmed]
  38. Clobazam for refractory focal epilepsy. A controlled trial. Schmidt, D., Rohde, M., Wolf, P., Roeder-Wanner, U. Arch. Neurol. (1986) [Pubmed]
  39. Epilepsy with electrical status epilepticus during slow sleep and secondary bilateral synchrony. Kobayashi, K., Nishibayashi, N., Ohtsuka, Y., Oka, E., Ohtahara, S. Epilepsia (1994) [Pubmed]
  40. Effects of clobazam and its active metabolite on GABA-activated currents in rat cerebral neurons in culture. Nakamura, F., Suzuki, S., Nishimura, S., Yagi, K., Seino, M. Epilepsia (1996) [Pubmed]
  41. The analysis of clobazam and its metabolite desmethylclobazam by high-performance liquid chromatography. Streete, J.M., Berry, D.J., Newbery, J.E. Therapeutic drug monitoring. (1991) [Pubmed]
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