4618 Clobazam Clobazam belongs to the 1,5-benzodiazepine class of drugs and is expected to have a better side-effect profile compared to older 1,4-benzodiazepines. It has been marketed as an anxiolytic since 1975 and an anticonvulsant since 1984. The oral preparation was FDA approved on October 21, 2011. An oral suspension is expected to be available in 2013. 22316-47-8 2789 C16H13ClN2O2 White powder. 180-182°C 188 mg/L After oral administration of clobazam, it is almost completely absorbed (87% of dose). Bioavailability relative to solution was almost at 100%. Food does not affect absorption. Tmax = 1-3 hours. Clobazam binds at distinct binding sites associated with the chloride ionopore at the post-synaptic GABA receptor. These GABA receptors are in various locations in the CNS (limbic, reticular formation) and clobazam increases the duration of time for which the chloride ionopore is open. As a result, hyper polarization and stabilization of the membrane occur as the post-synaptic inhibitory effect of GABA is enhanced. Clobazam is extensively metabolized in the liver via N-demethylation and hydroxylation. Clobazam has two major metabolites: N-desmethylclobazam (norclobazam) and 4'-hydroxyclobazam, the former of which is active. Norclobazam is one-fourth the potency of clobazam. The main enzyme that facilitates the process of N-demethylation is CYP3A4, and to a lesser extent by CYP2C19 and CYP2B6. Norclobazam itself is also metabolized via hydroxylation, primarily by CYP2C19. The formation of 4'-hydroxyclobazam is facilitated by CYP2C18 and CYP2C19. A factor in determining extent of metabolism is the genetic profile of the individual patient as CYP2C19 is a polymorphic enzyme. Route of Elimination: Clobazam is eliminated via the urine (~94%) as metabolites. Half Life: The mean elimination half life of an oral dose of clobazam 40 mg is 32 hours. It's main metabolite, norclobazam, as a half life of 57 hours. The half life in adult patients with epilepsy are higher than those that are healthy. No indication of carcinogenicity to humans (not listed by IARC). For treatment and management of epilepsy and seizures associated with Lennox-Gastaut syndrome, a difficult-to-treat form of childhood epilepsy. The most common adverse effects include somnolence, pyrexia, upper respiratory tract infection, and lethargy. General supportive measures should be employed, along with intravenous fluids, and an adequate airway maintained. Hypotension may be combated by the use of norepinephrine or metaraminol. Dialysis is of limited value. Flumazenil (Anexate) is a competitive benzodiazepine receptor antagonist that can be used as an antidote for benzodiazepine overdose. In particular, flumazenil is very effective at reversing the CNS depression associated with benzodiazepines but is less effective at reversing respiratory depression. Its use, however, is controversial as it has numerous contraindications. It is contraindicated in patients who are on long-term benzodiazepines, those who have ingested a substance that lowers the seizure threshold, or in patients who have tachycardia or a history of seizures. As a general rule, medical observation and supportive care are the mainstay of treatment of benzodiazepine overdose. Although benzodiazepines are absorbed by activated charcoal, gastric decontamination with activated charcoal is not beneficial in pure benzodiazepine overdose as the risk of adverse effects often outweigh any potential benefit from the procedure. It is recommended only if benzodiazepines have been taken in combination with other drugs that may benefit from decontamination. Gastric lavage (stomach pumping) or whole bowel irrigation are also not recommended. 2014-08-30T21:05:04Z 2026-03-31T19:07:26Z Clobazam 31413 DB00349 true CN1C2=C(C=C(Cl)C=C2)N(C2=CC=CC=C2)C(=O)CC1=O C16H13ClN2O2 InChI=1S/C16H13ClN2O2/c1-18-13-8-7-11(17)9-14(13)19(16(21)10-15(18)20)12-5-3-2-4-6-12/h2-9H,10H2,1H3 CXOXHMZGEKVPMT-UHFFFAOYSA-N 300.74 300.066555377 Exogenous Solid 2.12 CHEMBL70418 2687 <p>Hauptmann, K.H., Weber, K.-H., Zeile, K., Danneberg, P. and Giesemann, R.; South African<br /> Patent 68/0803; February 7,1968; assigned to Boehringer lngelheim GmbH, Germany.</p> CHEM003524 DTXSID2046759 NS00010408 7-chloro-1-methyl-5-phenyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine-2,4-dione