Clobazam

Identification

Summary

Clobazam is a benzodiazepine used as adjunct treatment in seizures associated with Lennox-Gastaut syndrome.

Brand Names

Onfi, Sympazan

Generic Name

Clobazam

DrugBank Accession Number

DB00349

Background

Clobazam belongs to the 1,5-benzodiazepine class of drugs and is marketed under different names, Onfi, Frisium, Urbanyl, and others.⁹. Clobazam was first synthesized in 1966 and first published in 1969, following the incidental synthesis and discovery of the first benzodiazepine chlordiazepoxide in the 1950s.¹² Unlike older 1,4-benzodiazepines, clobazam has a better side-effects profile, particularly less sedative and amnesic effects.^15,9 This is likely because of clobazam's higher affinity to the α₂ subunit of the GABA_A receptor, which mediates anxiolytic effects, than the α₁ subunit, which mediates sedative effect.⁹ Additionally, clobazam is believed to be a partial agonist to the GABA_A receptor rather than non-selective full receptor agonists like 1,4-benzodiazepines, thus potentially explaining the decreased incidence of sedative effects.^16,17

Clobazam has been marketed as an anxiolytic since 1975 and an anticonvulsant since 1984.^1,2 In October 21, 2011, the FDA approved clobazam as an adjunctive treatment for seizures associated with Lennox-Gastaut syndrome in adults and children aged two years and older.¹⁴ In 2005, clobazam also received approval from Health Canada as an add-on therapy for generalized tonic-clonic, myoclonic, and focal impaired awareness seizures.¹⁸

Type

Small Molecule

Groups

Approved, Illicit

Structure

3D

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MOLSDF3D-SDFPDBSMILESInChI

Similar Structures

Structure for Clobazam (DB00349)

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Weight

Average: 300.74
Monoisotopic: 300.066555377

Chemical Formula

C₁₆H₁₃ClN₂O₂

Synonyms

• 1-phenyl-5-methyl-8-chloro-1,2,4,5-tetrahydro-2,4-dioxo-3H-1,5-benzodiazepine
• 7-Chloro-1-methyl-5-phenyl-1,5-dihydro-benzo[b][1,4]diazepine-2,4-dione
• Clobazam
• Clobazamum

External IDs

• H 4723
• H-4723
• HR 376
• HR-376
• LM 2717
• LM-2717

Pharmacology

Indication

Clobazam is indicated for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients 2 years of age or older.²³

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Associated Conditions

• Anxiety
• Catamenial Epilepsy
• Refractory Status Epilepticus
• Seizures
• Status Epilepticus

Contraindications & Blackbox Warnings

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Pharmacodynamics

Clobazam belongs to the benzodiazepine class of drugs.²³ Clobazam acts on the GABA_A receptor to increase GABAnergic transmission, particularly chloride conductance in neurons.⁹ This causes neuronal hyperpolarization, resulting in an increase in the action potential threshold and reducing neuron firing frequency.^11,12 Consequently, the general neuronal activity of the central nervous system is depressed; therefore, clobazam can be used to treat diseases caused by excessive excitatory action potentials.¹²

The effect of clobazam 20 mg and 80 mg administered twice daily on QTc interval was evaluated in a randomized, evaluator-blinded, placebo-, and active-controlled (moxifloxacin 400 mg) parallel thorough QT study in 280 healthy subjects. In a study with demonstrated ability to detect small effects, the upper bound of the one-sided 95% confidence interval for the largest placebo-adjusted, baseline-corrected QTc based on the Fridericia correction method was below 10 ms, the threshold for regulatory concern. Thus, at a dose two times the maximum recommended dose, clobazam did not prolong the QTc interval to any clinically relevant extent.²³

Mechanism of action

The exact mechanism of action for clobazam, a 1,5-benzodiazepine, is not fully understood but is thought to involve the potentiation of GABAergic neurotransmission resulting from binding at the benzodiazepine site of the GABA_A receptor.²³ Specifically, clobazam binds to the interface of the α₂ and γ₂-subunit of the GABA_A receptor.⁹ It has a great affinity for the α₂ subunit than the α₁ subunit compared to other 1,4‐benzodiazepines.¹⁰Binding of clobazam to the GABA_A receptor causes chloride channels to open, resulting in an influx of chloride and thus hyperpolarization of neurons.⁹

Target	Actions	Organism
AGABA(A) Receptor	positive allosteric modulator	Humans
AGABA(A) Receptor Benzodiazepine Binding Site	ligand	Humans

Absorption

The peak plasma levels (Cmax) and the area under the curve (AUC) of clobazam are dose-proportional over the dose range of 10-80 mg following single- or multiple-dose administration of ONFI. Based on a population pharmacokinetic analysis, the pharmacokinetics of clobazam are linear from 5-160 mg/day.²³

Clobazam is rapidly and extensively absorbed following oral administration. The time to peak concentrations (T_max) of clobazam tablets under fasted conditions ranged from 0.5 to 4 hours after single- or multiple-dose administrations. The relative bioavailability of clobazam tablets compared to an oral solution is approximately 100%. After single-dose administration of the oral suspension under fasted conditions, the Tmax ranged from 0.5 to 2 hours. Based on exposure (C_max and AUC) of clobazam, clobazam tablets and suspension were shown to have similar bioavailability under fasted conditions. The administration of clobazam tablets with food or when crushed in applesauce does not affect absorption. Although not studied, the oral bioavailability of the oral suspension is unlikely to be affected under fed conditions.²³

Volume of distribution

Clobazam is lipophilic and distributes rapidly throughout the body. The apparent volume of distribution at steady state was approximately 100 L.²³

Protein binding

The in vitro plasma protein binding of clobazam and N-desmethylclobazam is approximately 80-90% and 70%, respectively.²³

Metabolism

Clobazam is extensively metabolized in the liver via N-demethylation and hydroxylation to form two major metabolites, N-desmethylclobazam (norclobazam) and 4'-hydroxyclobazam, respectively, with approximately 2% of the dose recovered in urine and 1% in feces as an unchanged drug.^23,13 The N-demethylation reaction is catalyzed primarily by CYP3A4 and to a lesser extent by CYP2C19 and CYP2B6. N-desmethylclobazam, an active metabolite, is the major circulating metabolite in humans, and at therapeutic doses, plasma concentrations are 3-5 times higher than those of the parent compound. Based on animal and in vitro receptor binding data, estimates of the relative potency of N-desmethylclobazam compared to the parent compound range from 1/5 to equal potency. N-desmethylclobazam is extensively hydroxylated, mainly by CYP2C19. N-desmethylclobazam and its metabolites comprise ~94% of the total drug-related components in urine.²³. The formation of 4'-hydroxyclobazam is facilitated by CYP2C18 and CYP2C19.¹³

The polymorphic CYP2C19 is the major contributor to the metabolism of the pharmacologically active N-desmethylclobazam. In CYP2C19 poor metabolizers, levels of N-desmethylclobazam were 5-fold higher in plasma and 2- to 3-fold higher in the urine than in CYP2C19 extensive metabolizers.²³

Hover over products below to view reaction partners

• Clobazam
  • N-desmethylclobazam
    • 4'-hydroxy-N-desmethylclobazam
  • 4'-hydroxyclobazam
    • 4'-hydroxy-N-desmethylclobazam

Route of elimination

N-desmethylclobazam and its metabolites comprise ~94% of the total drug-related components in urine. Following a single oral dose of radiolabeled drug, approximately 11% of the dose was excreted in the feces and approximately 82% was excreted in the urine.²³

Half-life

The estimated mean elimination half-lives (t½) of clobazam and N-desmethylclobazam were 36-42 hours and 71-82 hours, respectively.²³

Clearance

After a 20 to 40 mg/day administration of clobazam, the oral clearance is calculated to be 1.9 to 2.3 L/h.⁸

Adverse Effects

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Toxicity

Neonates born to mothers using benzodiazepines late in pregnancy have been reported to experience symptoms of sedation and/or neonatal withdrawal [see Warnings and Precautions (5.8) and Clinical Considerations]. Available data from published observational studies of pregnant women exposed to benzodiazepines do not report a clear association between benzodiazepines and major birth defects.²³

Administration of clobazam to pregnant rats and rabbits during the period of organogenesis or to rats throughout pregnancy and lactation resulted in developmental toxicity, including increased incidences of fetal malformations and mortality, at plasma exposures for clobazam and its major active metabolite, N-desmethylclobazam, below those expected at therapeutic doses in patients. Data for other benzodiazepines suggest the possibility of long-term effects on neurobehavioral and immunological function in animals following prenatal exposure to benzodiazepines at clinically relevant doses. ONFI should be used during pregnancy only if the potential benefit to the mother justifies the potential risk to the fetus. Advise a pregnant woman and women of childbearing age of the potential risk to a fetus.²³

Benzodiazepines cross the placenta and may produce respiratory depression, hypotonia, and sedation in neonates. Monitor neonates exposed to clobazam during pregnancy or labor for signs of sedation, respiratory depression, hypotonia, and feeding problems. Monitor neonates exposed to clobazam during pregnancy for signs of withdrawal. Manage these neonates accordingly [see Warnings and Precautions (5.8)].²³

The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.²³

Administration of clobazam to rats prior to and during mating and early gestation resulted in adverse effects on fertility and early embryonic development at plasma exposures for clobazam and its major active metabolite, N-desmethylclobazam, below those in humans at the MRHD [see Nonclinical Toxicology (13.1)].²³

In a study in which clobazam (0, 4, 36, or 120 mg/kg/day) was orally administered to rats during the juvenile period of development (postnatal days 14 to 48), adverse effects on growth (decreased bone density and bone length) and behavior (altered motor activity and auditory startle response; learning deficit) were observed at the high dose. The effect on bone density, but not on behavior, was reversible when the drug was discontinued. The no-effect level for juvenile toxicity (36 mg/kg/day) was associated with plasma exposures (AUC) to clobazam and its major active metabolite, N-desmethylclobazam, less than those expected at therapeutic doses in pediatric patients.²³

In mice, oral administration of clobazam (0, 6, 12, or 24 mg/kg/day) for 2 years did not result in an increase in tumors. The highest dose tested was approximately 3 times the maximum recommended human dose (MRHD) of 40 mg/day, based on body surface area (mg/m2).²³

In rats, oral administration of clobazam for 2 years resulted in increases in tumors of the thyroid gland (follicular cell adenoma and carcinoma) and liver (hepatocellular adenoma) at the mid and high doses. The low dose, not associated with an increase in tumors, was associated with plasma exposures (AUC) for clobazam and its major active metabolite, N-desmethylclobazam, less than that in humans at the MRHD.²³

Clobazam and the major active metabolite, N-desmethylclobazam, were negative for genotoxicity, based on data from a battery of in vitro (bacteria reverse mutation, mammalian clastogenicity) and in vivo (mouse micronucleus) assays.²³

In a fertility study in which clobazam (50, 350, or 750 mg/kg/day, corresponding to 12, 84, and 181 times the oral Maximum Recommended Human Dose, MRHD, of 40 mg/day based on mg/m2 body surface) was orally administered to male and female rats prior to and during mating and continuing in females to gestation day 6, increases in abnormal sperm and pre-implantation loss were observed at the highest dose tested. The no-effect level for fertility and early embryonic development in rats was associated with plasma exposures (AUC) for clobazam and its major active metabolite, N-desmethylclobazam, less than those in humans at the maximum recommended human dose of 40 mg/day.²³

Clobazam is a benzodiazepine and a CNS depressant with a potential for abuse and addiction. Abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects. Misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a health care provider or for whom it was not prescribed. Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence. Even taking benzodiazepines as prescribed may put patients at risk for abuse and misuse of their medication. Abuse and misuse of benzodiazepines may lead to addiction.²³

Abuse and misuse of benzodiazepines often (but not always) involve the use of doses greater than the maximum recommended dosage and commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes, including respiratory depression, overdose, or death. Benzodiazepines are often sought by individuals who abuse drugs and other substances, and by individuals with addictive disorders [see Warnings and Precautions (5.2)].²³

The following adverse reactions have occurred with benzodiazepine abuse and/or misuse: abdominal pain, amnesia, anorexia, anxiety, aggression, ataxia, blurred vision, confusion, depression, disinhibition, disorientation, dizziness, euphoria, impaired concentration and memory, indigestion, irritability, muscle pain, slurred speech, tremors, and vertigo.²³

The following severe adverse reactions have occurred with benzodiazepine abuse and/or misuse: delirium, paranoia, suicidal ideation and behavior, seizures, coma, breathing difficulty, and death. Death is more often associated with polysubstance use (especially benzodiazepines with other CNS depressants such as opioids and alcohol).²³

The World Health Organization epidemiology database contains reports of drug abuse, misuse, and overdoses associated with clobazam.²³

Clobazam may produce physical dependence from continued therapy. Physical dependence is a state that develops as a result of physiological adaptation in response to repeated drug use, manifested by withdrawal signs and symptoms after abrupt discontinuation or a significant dose reduction of a drug. Abrupt discontinuation or rapid dosage reduction of benzodiazepines or administration of flumazenil, a benzodiazepine antagonist, may precipitate acute withdrawal reactions, including seizures, which can be life-threatening.²³

Patients at an increased risk of withdrawal adverse reactions after benzodiazepine discontinuation or rapid dosage reduction include those who take higher dosages (i.e., higher and/or more frequent doses) and those who have had longer durations of use [see Warnings and Precautions (5.3)]. In clinical trials, cases of dependency were reported following the abrupt discontinuation of clobazam.²³

Acute withdrawal signs and symptoms associated with benzodiazepines have included abnormal involuntary movements, anxiety, blurred vision, depersonalization, depression, derealization, dizziness, fatigue, gastrointestinal adverse reactions (e.g.,nausea, vomiting, diarrhea, weight loss, decreased appetite), headache, hyperacusis,hypertension, irritability, insomnia, memory impairment, muscle pain and stiffness, panic attacks, photophobia, restlessness, tachycardia, and tremor. More severe acute withdrawal signs and symptoms, including life-threatening reactions, have included catatonia, convulsions, delirium tremens, depression, hallucinations, mania, psychosis, seizures, and suicidality.²³

Protracted withdrawal syndrome associated with benzodiazepines is characterized by anxiety, cognitive impairment, depression, insomnia, formication, motor symptoms (e.g., weakness, tremor, muscle twitches), paresthesia, and tinnitus that persists beyond 4 to 6 weeks after initial benzodiazepine withdrawal. Protracted withdrawal symptoms may last weeks to more than 12 months. As a result, there may be difficulty in differentiating withdrawal symptoms from potential re-emergence or continuation of symptoms for which the benzodiazepine was being used.²³

Tolerance to clobazam may develop from continued therapy. Tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose). Tolerance to the therapeutic effect of clobazam may develop; however, little tolerance develops to the amnestic reactions and other cognitive impairments caused by benzodiazepines.²³

Overdosage of benzodiazepines is characterized by central nervous system depression ranging from drowsiness to coma. In mild to moderate cases, symptoms can include drowsiness, confusion, dysarthria, lethargy, hypnotic state, diminished reflexes, ataxia, and hypotonia. Rarely, paradoxical or disinhibitory reactions (including agitation, irritability, impulsivity, violent behavior, confusion, restlessness, excitement, and talkativeness) may occur. In severe overdosage cases, patients may develop respiratory depression and coma. Overdosage of benzodiazepines in combination with other CNS depressants (including alcohol and opioids) may be fatal [see Warnings and Precautions (5.2)]. Markedly abnormal (lowered or elevated) blood pressure, heart rate, or respiratory rate raises the concern that additional drugs and/or alcohol are involved in the overdosage.²³

In managing benzodiazepine overdosage, employ general supportive measures, including intravenous fluids and airway maintenance. Flumazenil, a specific benzodiazepine receptor antagonist indicated for the complete or partial reversal of the sedative effects of benzodiazepines in the management of benzodiazepine overdosage, can lead to withdrawal and adverse reactions, including seizures, particularly in the context of mixed overdosage with drugs that increase seizure risk (e.g., tricyclic and tetracyclic antidepressants) and in patients with long-term benzodiazepine use and physical dependency. The risk of withdrawal seizures with flumazenil may be increased in patients with epilepsy. Flumazenil is contraindicated in patients who have received a benzodiazepine for control of a potentially life-threatening condition (e.g., status epilepticus). If the decision is made to use flumazenil, it should be used as an adjunct to, not as a substitute for, supportive management of benzodiazepine overdosage. See the flumazenil injection Prescribing Information.²³

Consider contacting the Poison Help line (1-800-222-1222) or a medical toxicologist for additional overdosage management recommendations.²³

Pathways

Not Available

Pharmacogenomic Effects/ADRs

Interacting Gene/Enzyme	Allele name	Genotype(s)	Defining Change(s)	Type(s)	Description	Details
Cytochrome P450 2C19	CYP2C19*2	(A;A) / (A;G)	G > A/C	ADR Directly Studied	Patients with this genotype have reduced metabolism of clobazam.	Details
Cytochrome P450 2C19	CYP2C19*2A	Not Available	681G>A	ADR Inferred	Clobazem is metabolized into N-desmethylclobazem (NCLB) mostly by CYP3A4. NCLB is primarily metabolized by 2C19. Those with one 2C19*2 allele mutation (1*/2*) are intermediate metabolizers of NCLB. Those with two (2*/2*) mutations will metabolize NCLB poorly in comparisone to extensive metabolizers (1*/1*). Levels of NCLB can be five times higher in poor metabolizers, and two times higher in intermediate metabolizers as compared to individuals who are extensive metabolizers. The safety and efficacy of clobazem may be affected by polymorphic expression of CYP2C19*2.	Details
Cytochrome P450 2C19	CYP2C19*2B	Not Available	681G>A	ADR Inferred	Clobazem is metabolized into N-desmethylclobazem (NCLB) mostly by CYP3A4. NCLB is primarily metabolized by 2C19. Those with one 2C19*2 allele mutation (1*/2*) are intermediate metabolizers of NCLB. Those with two (2*/2*) mutations will metabolize NCLB poorly in comparisone to extensive metabolizers (1*/1*). Levels of NCLB can be five times higher in poor metabolizers, and two times higher in intermediate metabolizers as compared to individuals who are extensive metabolizers. The safety and efficacy of clobazem may be affected by polymorphic expression of CYP2C19*2.	Details
Cytochrome P450 2C19	CYP2C19*3	Not Available	636G>A	ADR Inferred	Clobazem is metabolized into N-desmethylclobazem (NCLB) mostly by CYP3A4. NCLB is primarily metabolized by 2C19. Those with one 2C19*2 allele mutation (1*/2*) are intermediate metabolizers of NCLB. Those with two (2*/2*) mutations will metabolize NCLB poorly in comparisone to extensive metabolizers (1*/1*). Levels of NCLB can be five times higher in poor metabolizers, and two times higher in intermediate metabolizers as compared to individuals who are extensive metabolizers. The safety and efficacy of clobazem may be affected by polymorphic expression of CYP2C19*2.	Details
Cytochrome P450 2C19	CYP2C19*4	Not Available	1A>G	ADR Inferred	Clobazem is metabolized into N-desmethylclobazem (NCLB) mostly by CYP3A4. NCLB is primarily metabolized by 2C19. Those with one 2C19*2 allele mutation (1*/2*) are intermediate metabolizers of NCLB. Those with two (2*/2*) mutations will metabolize NCLB poorly in comparisone to extensive metabolizers (1*/1*). Levels of NCLB can be five times higher in poor metabolizers, and two times higher in intermediate metabolizers as compared to individuals who are extensive metabolizers. The safety and efficacy of clobazem may be affected by polymorphic expression of CYP2C19*2.	Details
Cytochrome P450 2C19	CYP2C19*5	Not Available	1297C>T	ADR Inferred	Clobazem is metabolized into N-desmethylclobazem (NCLB) mostly by CYP3A4. NCLB is primarily metabolized by 2C19. Those with one 2C19*2 allele mutation (1*/2*) are intermediate metabolizers of NCLB. Those with two (2*/2*) mutations will metabolize NCLB poorly in comparisone to extensive metabolizers (1*/1*). Levels of NCLB can be five times higher in poor metabolizers, and two times higher in intermediate metabolizers as compared to individuals who are extensive metabolizers. The safety and efficacy of clobazem may be affected by polymorphic expression of CYP2C19*2.	Details
Cytochrome P450 2C19	CYP2C19*6	Not Available	395G>A	ADR Inferred	Clobazem is metabolized into N-desmethylclobazem (NCLB) mostly by CYP3A4. NCLB is primarily metabolized by 2C19. Those with one 2C19*2 allele mutation (1*/2*) are intermediate metabolizers of NCLB. Those with two (2*/2*) mutations will metabolize NCLB poorly in comparisone to extensive metabolizers (1*/1*). Levels of NCLB can be five times higher in poor metabolizers, and two times higher in intermediate metabolizers as compared to individuals who are extensive metabolizers. The safety and efficacy of clobazem may be affected by polymorphic expression of CYP2C19*2.	Details
Cytochrome P450 2C19	CYP2C19*7	Not Available	19294T>A	ADR Inferred	Clobazem is metabolized into N-desmethylclobazem (NCLB) mostly by CYP3A4. NCLB is primarily metabolized by 2C19. Those with one 2C19*2 allele mutation (1*/2*) are intermediate metabolizers of NCLB. Those with two (2*/2*) mutations will metabolize NCLB poorly in comparisone to extensive metabolizers (1*/1*). Levels of NCLB can be five times higher in poor metabolizers, and two times higher in intermediate metabolizers as compared to individuals who are extensive metabolizers. The safety and efficacy of clobazem may be affected by polymorphic expression of CYP2C19*2.	Details
Cytochrome P450 2C19	CYP2C19*22	Not Available	557G>C / 991A>G	ADR Inferred	Clobazem is metabolized into N-desmethylclobazem (NCLB) mostly by CYP3A4. NCLB is primarily metabolized by 2C19. Those with one 2C19*2 allele mutation (1*/2*) are intermediate metabolizers of NCLB. Those with two (2*/2*) mutations will metabolize NCLB poorly in comparisone to extensive metabolizers (1*/1*). Levels of NCLB can be five times higher in poor metabolizers, and two times higher in intermediate metabolizers as compared to individuals who are extensive metabolizers. The safety and efficacy of clobazem may be affected by polymorphic expression of CYP2C19*2.	Details
Cytochrome P450 2C19	CYP2C19*24	Not Available	99C>T / 991A>G  … show all	ADR Inferred	Clobazem is metabolized into N-desmethylclobazem (NCLB) mostly by CYP3A4. NCLB is primarily metabolized by 2C19. Those with one 2C19*2 allele mutation (1*/2*) are intermediate metabolizers of NCLB. Those with two (2*/2*) mutations will metabolize NCLB poorly in comparisone to extensive metabolizers (1*/1*). Levels of NCLB can be five times higher in poor metabolizers, and two times higher in intermediate metabolizers as compared to individuals who are extensive metabolizers. The safety and efficacy of clobazem may be affected by polymorphic expression of CYP2C19*2.	Details
Cytochrome P450 2C19	CYP2C19*35	Not Available	12662A>G	ADR Inferred	Clobazem is metabolized into N-desmethylclobazem (NCLB) mostly by CYP3A4. NCLB is primarily metabolized by 2C19. Those with one 2C19*2 allele mutation (1*/2*) are intermediate metabolizers of NCLB. Those with two (2*/2*) mutations will metabolize NCLB poorly in comparisone to extensive metabolizers (1*/1*). Levels of NCLB can be five times higher in poor metabolizers, and two times higher in intermediate metabolizers as compared to individuals who are extensive metabolizers. The safety and efficacy of clobazem may be affected by polymorphic expression of CYP2C19*2.	Details

Interactions

Drug Interactions

This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.

• Approved
• Vet approved
• Nutraceutical
• Illicit
• Withdrawn
• Investigational
• Experimental
• All Drugs

Drug	Interaction
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1,2-Benzodiazepine	The risk or severity of sedation, somnolence, and CNS depression can be increased when Clobazam is combined with 1,2-Benzodiazepine.
Abacavir	Clobazam may decrease the excretion rate of Abacavir which could result in a higher serum level.
Abametapir	The serum concentration of Clobazam can be increased when it is combined with Abametapir.
Abatacept	The metabolism of Clobazam can be increased when combined with Abatacept.
Abemaciclib	The metabolism of Abemaciclib can be increased when combined with Clobazam.
Abrocitinib	The serum concentration of Clobazam can be increased when it is combined with Abrocitinib.
Acalabrutinib	The metabolism of Acalabrutinib can be increased when combined with Clobazam.
Acebutolol	The serum concentration of Acebutolol can be increased when it is combined with Clobazam.
Aceclofenac	Aceclofenac may decrease the excretion rate of Clobazam which could result in a higher serum level.
Acemetacin	Acemetacin may decrease the excretion rate of Clobazam which could result in a higher serum level.

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Food Interactions

• Avoid alcohol. Alcohol increases clobazam absorption by 50%.
• Take with or without food. The absorption is unaffected by food.

Products

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Product Images

International/Other Brands

Aedon (Sanofi-Aventis) / Castilium (Sanofi-Aventis) / Clobam (Square) / Clobamax (Sherfarma) / Frisium (Sanofi-Aventis) / Grifoclobam (Chile) / Mystan (Dainippon Sumitomo) / Noiafren (Sanofi Aventis) / Sederlona / Urbanil (Sanofi-Aventis) / Urbanol (Sanofi-Aventis) / Urbanyl (Sanofi-Aventis) / Venium (Hudson)

Brand Name Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End	Region	Image
Clobazam-10	Tablet	10 mg	Oral	Pro Doc Limitee	2003-12-09	2017-05-05
Frisium Tab 10mg	Tablet	10 mg / tab	Oral	Hoechst Canada Inc.	1991-12-31	1996-08-29
Frisium Tablet 10mg	Tablet	10 mg	Oral	Lundbeck Pharmaceuticals Llc	1997-03-24	2018-08-31
Frisium Tablets 10mg	Tablet	10 mg	Oral	Hoechst Roussel Canada Inc.	1994-12-31	1999-08-11
Onfi	Tablet	10 mg/1	Oral	Lundbeck Inc.	2011-10-21	2011-10-31
Onfi	Tablet	10 mg/1	Oral	Lundbeck Pharmaceuticals Llc	2013-12-10	Not applicable
Onfi	Suspension	2.5 mg/1mL	Oral	Lundbeck Pharmaceuticals Llc	2012-12-14	Not applicable
Onfi	Tablet	5 mg/1	Oral	Lundbeck Inc.	2011-10-21	2011-10-31
Onfi	Tablet	20 mg/1	Oral	Lundbeck Inc.	2011-10-21	2011-10-31
Onfi	Tablet	20 mg/1	Oral	Lundbeck Pharmaceuticals Llc	2013-12-10	Not applicable

Generic Prescription Products

Name	Dosage	Strength	Route	Labeller	Marketing Start	Marketing End	Region	Image
Apo-clobazam	Tablet	10 mg	Oral	Apotex Corporation	2001-11-28	Not applicable
Clobazam	Tablet	20 mg/1	Oral	Zydus Lifesciences Limited	2018-10-22	Not applicable
Clobazam	Tablet	10 mg/1	Oral	American Health Packaging	2019-01-17	Not applicable
Clobazam	Tablet	20 mg/1	Oral	West-Ward Pharmaceuticals Corp.	2018-10-22	Not applicable
Clobazam	Tablet	10 mg/1	Oral	Lupin Pharmaceuticals, Inc.	2019-05-08	Not applicable
Clobazam	Tablet	20 mg/1	Oral	Bionpharma Inc.	2017-10-20	Not applicable
Clobazam	Tablet	10 mg/1	Oral	Msn Laboratories Private Limited	2021-05-12	Not applicable
Clobazam	Tablet	10 mg/1	Oral	Sandoz Inc.	2018-10-23	Not applicable
Clobazam	Suspension	2.5 mg/1mL	Oral	Mylan Pharmaceuticals Inc.	2018-11-07	Not applicable
Clobazam	Suspension	2.5 mg/1mL	Oral	Lannett Company, Inc.	2020-04-24	2023-06-30

Categories

ATC Codes

N05BA09 — Clobazam

• N05BA — Benzodiazepine derivatives
• N05B — ANXIOLYTICS
• N05 — PSYCHOLEPTICS
• N — NERVOUS SYSTEM

Drug Categories

• Anti-Anxiety Agents
• Anticonvulsants
• Benzazepines
• Benzodiazepines and benzodiazepine derivatives
• Central Nervous System Agents
• Central Nervous System Depressants
• Cytochrome P-450 CYP1A2 Substrates
• Cytochrome P-450 CYP2B6 Substrates
• Cytochrome P-450 CYP2C18 Substrates
• Cytochrome P-450 CYP2C19 Substrates
• Cytochrome P-450 CYP2C8 Substrates
• Cytochrome P-450 CYP2C9 Inhibitors
• Cytochrome P-450 CYP2C9 Inhibitors (weak)
• Cytochrome P-450 CYP2D6 Inhibitors
• Cytochrome P-450 CYP2D6 Inhibitors (moderate)
• Cytochrome P-450 CYP3A Inducers
• Cytochrome P-450 CYP3A Substrates
• Cytochrome P-450 CYP3A4 Inducers
• Cytochrome P-450 CYP3A4 Inducers (strength unknown)
• Cytochrome P-450 CYP3A4 Inducers (weak)
• Cytochrome P-450 CYP3A4 Substrates
• Cytochrome P-450 CYP3A5 Substrates
• Cytochrome P-450 CYP3A7 Substrates
• Cytochrome P-450 Enzyme Inducers
• Cytochrome P-450 Enzyme Inhibitors
• Cytochrome P-450 Substrates
• Drugs that are Mainly Renally Excreted
• GABA Agents
• GABA Agonists
• GABA-A Receptor Agonists
• Heterocyclic Compounds, Fused-Ring
• Nervous System
• Neurotransmitter Agents
• P-glycoprotein substrates
• Psycholeptics
• Psychotropic Drugs
• Tranquilizing Agents
• UGT1A4 Inhibitors
• UGT1A6 Inhibitors

Chemical TaxonomyProvided by Classyfire

Description

This compound belongs to the class of organic compounds known as benzodiazepines. These are organic compounds containing a benzene ring fused to either isomers of diazepine(unsaturated seven-member heterocycle with two nitrogen atoms replacing two carbon atoms).

Kingdom

Organic compounds

Super Class

Organoheterocyclic compounds

Class

Benzodiazepines

Sub Class

Not Available

Direct Parent

Benzodiazepines

Alternative Parents

1,4-diazepines / Benzene and substituted derivatives / Aryl chlorides / 1,3-dicarbonyl compounds / Tertiary carboxylic acid amides / Lactams / Azacyclic compounds / Organopnictogen compounds / Organonitrogen compounds / Organochlorides / Organic oxides / Hydrocarbon derivatives

show 2 more

Substituents

1,3-dicarbonyl compound / Aromatic heteropolycyclic compound / Aryl chloride / Aryl halide / Azacycle / Benzenoid / Benzodiazepine / Carbonyl group / Carboxamide group / Carboxylic acid derivative / Hydrocarbon derivative / Lactam / Monocyclic benzene moiety / Organic nitrogen compound / Organic oxide / Organic oxygen compound / Organochloride / Organohalogen compound / Organonitrogen compound / Organooxygen compound / Organopnictogen compound / Para-diazepine / Tertiary carboxylic acid amide

show 13 more

Molecular Framework

Aromatic heteropolycyclic compounds

External Descriptors

organochlorine compound, 1,4-benzodiazepinone (CHEBI:31413)

Affected organisms

• Humans and other mammals

Chemical Identifiers

UNII

2MRO291B4U

CAS number

22316-47-8

InChI Key

CXOXHMZGEKVPMT-UHFFFAOYSA-N

InChI

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

IUPAC Name

7-chloro-1-methyl-5-phenyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepine-2,4-dione

SMILES

CN1C2=C(C=C(Cl)C=C2)N(C2=CC=CC=C2)C(=O)CC1=O

References

Synthesis Reference

Hauptmann, K.H., Weber, K.-H., Zeile, K., Danneberg, P. and Giesemann, R.; South African Patent 68/0803; February 7,1968; assigned to Boehringer lngelheim GmbH, Germany.

General References

1. Freche C: [Study of an anxiolytic, clobazam, in otorhinolaryngology in psychosomatic pharyngeal manifestations]. Sem Hop Ther. 1975 Apr;51(4):261-3. [Article]
2. Authors unspecified: Clobazam in treatment of refractory epilepsy: the Canadian experience. A retrospective study. Canadian Clobazam Cooperative Group. Epilepsia. 1991 May-Jun;32(3):407-16. [Article]
3. Wildin JD, Pleuvry BJ, Mawer GE, Onon T, Millington L: Respiratory and sedative effects of clobazam and clonazepam in volunteers. Br J Clin Pharmacol. 1990 Feb;29(2):169-77. [Article]
4. Kilpatrick C, Bury R, Fullinfaw R, Moulds R: Clobazam in the treatment of epilepsy. Clin Exp Neurol. 1987;23:139-44. [Article]
5. Giarratano M, Standley K, Benbadis SR: Clobazam for treatment of epilepsy. Expert Opin Pharmacother. 2012 Feb;13(2):227-33. doi: 10.1517/14656566.2012.647686. Epub 2012 Jan 13. [Article]
6. Yang LP, Scott LJ: Clobazam : in patients with Lennox-Gastaut syndrome. CNS Drugs. 2012 Nov;26(11):983-91. doi: 10.1007/s40263-012-0007-0. [Article]
7. Walzer M, Bekersky I, Blum RA, Tolbert D: Pharmacokinetic drug interactions between clobazam and drugs metabolized by cytochrome P450 isoenzymes. Pharmacotherapy. 2012 Apr;32(4):340-53. doi: 10.1002/j.1875-9114.2012.01028.x. Epub 2012 Mar 15. [Article]
8. Tolbert D, Larsen F: A Comprehensive Overview of the Clinical Pharmacokinetics of Clobazam. J Clin Pharmacol. 2019 Jan;59(1):7-19. doi: 10.1002/jcph.1313. Epub 2018 Oct 4. [Article]
9. Gauthier AC, Mattson RH: Clobazam: A Safe, Efficacious, and Newly Rediscovered Therapeutic for Epilepsy. CNS Neurosci Ther. 2015 Jul;21(7):543-8. doi: 10.1111/cns.12399. Epub 2015 Apr 28. [Article]
10. Jensen HS, Nichol K, Lee D, Ebert B: Clobazam and its active metabolite N-desmethylclobazam display significantly greater affinities for alpha(2)- versus alpha(1)-GABA(A)-receptor complexes. PLoS One. 2014 Feb 12;9(2):e88456. doi: 10.1371/journal.pone.0088456. eCollection 2014. [Article]
11. Nakamura F, Suzuki S, Nishimura S, Yagi K, Seino M: Effects of clobazam and its active metabolite on GABA-activated currents in rat cerebral neurons in culture. Epilepsia. 1996 Aug;37(8):728-35. doi: 10.1111/j.1528-1157.1996.tb00643.x. [Article]
12. Stafstrom CE, Carmant L: Seizures and epilepsy: an overview for neuroscientists. Cold Spring Harb Perspect Med. 2015 Jun 1;5(6):a022426. doi: 10.1101/cshperspect.a022426. [Article]
13. Giraud C, Tran A, Rey E, Vincent J, Treluyer JM, Pons G: In vitro characterization of clobazam metabolism by recombinant cytochrome P450 enzymes: importance of CYP2C19. Drug Metab Dispos. 2004 Nov;32(11):1279-86. [Article]
14. Guerreiro CA: Clobazam: the phoenix drug (from the very old to the brand new). Indian J Med Res. 2014 Aug;140(2):163-4. [Article]
15. Sankar R: GABA(A) receptor physiology and its relationship to the mechanism of action of the 1,5-benzodiazepine clobazam. CNS Drugs. 2012 Mar 1;26(3):229-44. doi: 10.2165/11599020-000000000-00000. [Article]
16. Pernea M, Sutcliffe AG: Clobazam and Its Use in Epilepsy. Pediatr Rep. 2016 Jun 15;8(2):6516. doi: 10.4081/pr.2016.6516. eCollection 2016 Jun 15. [Article]
17. Faulkner MA: Comprehensive overview: efficacy, tolerability, and cost-effectiveness of clobazam in Lennox-Gastaut syndrome. Ther Clin Risk Manag. 2015 Jun 8;11:905-14. doi: 10.2147/TCRM.S55930. eCollection 2015. [Article]
18. Humayun MJ, Samanta D, Carson RP: Clobazam. . [Article]
19. Tanabe T, Awaya Y, Matsuishi T, Iyoda K, Nagai T, Kurihara M, Yamamoto K, Minagawa K, Maekawa K: Management of and prophylaxis against status epilepticus in children with severe myoclonic epilepsy in infancy (SMEI; Dravet syndrome)--a nationwide questionnaire survey in Japan. Brain Dev. 2008 Nov;30(10):629-35. doi: 10.1016/j.braindev.2008.03.002. [Article]
20. Sivakumar S, Ibrahim M, Parker D Jr, Norris G, Shah A, Mohamed W: Clobazam: An effective add-on therapy in refractory status epilepticus. Epilepsia. 2015 Jun;56(6):e83-9. doi: 10.1111/epi.13013. Epub 2015 May 12. [Article]
21. Feely M, Calvert R, Gibson J: Clobazam in catamenial epilepsy. A model for evaluating anticonvulsants. Lancet. 1982 Jul 10;2(8289):71-3. doi: 10.1016/s0140-6736(82)91691-9. [Article]
22. Rickels K, Brown AS, Cohen D, Harris H, Hurowitz A, Lindenbaum EJ, Ross HA, Weinstock R, Wiseman K, Zal M: Clobazam and diazepam in anxiety. Clin Pharmacol Ther. 1981 Jul;30(1):95-100. doi: 10.1038/clpt.1981.132. [Article]
23. FDA Approved Drug Products: ONFI® (clobazam) tablets, for oral use, CIV [Link]
24. DailyMed Label: ONFI (clobazam) oral suspension or tablets, CIV [Link]
25. Clobazam MSDS LGC [Link]
26. Clobazam (T3D4564) [Link]
27. Health Canada Approved Drug Proucts: APO-CLOBAZAM (Clobazam) tablets, for oral use [Link]

External Links

Human Metabolome Database

HMDB0014493

KEGG Drug

D01253

PubChem Compound

2789

PubChem Substance

46506115

ChemSpider

2687

BindingDB

50247888

RxNav

21241

ChEBI

31413

ChEMBL

CHEMBL70418

ZINC

ZINC000000001175

Therapeutic Targets Database

DAP000672

PharmGKB

PA10888

RxList

RxList Drug Page

Drugs.com

Drugs.com Drug Page

Wikipedia

Clobazam

FDA label

Download (595 KB)

MSDS

Download (57.5 KB)

Clinical Trials

Clinical Trials

Phase	Status	Purpose	Conditions	Count
4	Completed	Treatment	Anxiety / Epilepsies	1
4	Recruiting	Treatment	Drug-resistant Epilepsy	1
4	Unknown Status	Treatment	Epilepsies	2
4	Unknown Status	Treatment	Refractory Epilepsy	1
3	Completed	Basic Science	Back Pain Lower Back	1
3	Completed	Treatment	Epilepsies / Epilepsy, Generalized / Seizures	1
3	Completed	Treatment	Lennox-Gastaut Syndrome	1
3	Completed	Treatment	Pain	1
3	Terminated	Treatment	Anxiety Disorders / Dementia / Depression / Psychosomatic Disorders / Schizophrenia	1
3	Terminated	Treatment	Dravet Syndrome (DS)	1

Pharmacoeconomics

Manufacturers

Not Available

Packagers

Not Available

Dosage Forms

Form	Route	Strength
Solution	Oral	2.5 mg/1mL
Suspension	Oral	2.5 mg/1mL
Suspension	Oral	1 mg/ml
Suspension	Oral
Capsule
Tablet	Oral	10.00 mg
Tablet	Oral
Tablet	Oral	10 mg / tab
Tablet	Oral	10 mg
Tablet	Oral	20 mg
Tablet	Oral	10 mg/1
Tablet	Oral	20 mg/1
Tablet	Oral	5 mg/1
Film	Oral	10 mg/1
Film	Oral	20 mg/1
Film	Oral	5 mg/1
Suspension	Oral	0.25 g

Prices

Unit description	Cost	Unit
Apo-Clobazam 10 mg Tablet	0.23USD	tablet
Novo-Clobazam 10 mg Tablet	0.23USD	tablet
Pms-Clobazam 10 mg Tablet	0.23USD	tablet

DrugBank does not sell nor buy drugs. Pricing information is supplied for informational purposes only.

Patents

Patent Number	Pediatric Extension	Approved	Expires (estimated)	Region
US8603514	No	2013-12-10	2024-04-03
US8765167	No	2014-07-01	2024-02-20
US11541002	No	2019-09-05	2039-09-05

Properties

State

Solid

Experimental Properties

Property	Value	Source
melting point (°C)	182-185ºC	L44888
water solubility	188 mg/L	L44983
logP	2.12	HENCZI,M ET AL. (1995),L44973

Predicted Properties

Property	Value	Source
Water Solubility	0.164 mg/mL	ALOGPS
logP	2.14	ALOGPS
logP	2.55	Chemaxon
logS	-3.3	ALOGPS
pKa (Strongest Acidic)	5.82	Chemaxon
pKa (Strongest Basic)	-6.7	Chemaxon
Physiological Charge	-1	Chemaxon
Hydrogen Acceptor Count	2	Chemaxon
Hydrogen Donor Count	0	Chemaxon
Polar Surface Area	40.62 Å2	Chemaxon
Rotatable Bond Count	1	Chemaxon
Refractivity	80.3 m3·mol-1	Chemaxon
Polarizability	30.07 Å3	Chemaxon
Number of Rings	3	Chemaxon
Bioavailability	1	Chemaxon
Rule of Five	Yes	Chemaxon
Ghose Filter	Yes	Chemaxon
Veber's Rule	No	Chemaxon
MDDR-like Rule	No	Chemaxon

Predicted ADMET Features

Property	Value	Probability
Human Intestinal Absorption	+	0.99
Blood Brain Barrier	+	0.9904
Caco-2 permeable	+	0.7487
P-glycoprotein substrate	Non-substrate	0.5733
P-glycoprotein inhibitor I	Non-inhibitor	0.5462
P-glycoprotein inhibitor II	Non-inhibitor	0.9204
Renal organic cation transporter	Non-inhibitor	0.7373
CYP450 2C9 substrate	Non-substrate	0.7058
CYP450 2D6 substrate	Non-substrate	0.8607
CYP450 3A4 substrate	Substrate	0.6871
CYP450 1A2 substrate	Non-inhibitor	0.6829
CYP450 2C9 inhibitor	Non-inhibitor	0.5296
CYP450 2D6 inhibitor	Non-inhibitor	0.8908
CYP450 2C19 inhibitor	Non-inhibitor	0.5791
CYP450 3A4 inhibitor	Inhibitor	0.7008
CYP450 inhibitory promiscuity	Low CYP Inhibitory Promiscuity	0.5308
Ames test	Non AMES toxic	0.9132
Carcinogenicity	Non-carcinogens	0.7846
Biodegradation	Not ready biodegradable	1.0
Rat acute toxicity	1.7313 LD50, mol/kg	Not applicable
hERG inhibition (predictor I)	Weak inhibitor	0.9896
hERG inhibition (predictor II)	Non-inhibitor	0.8651

ADMET data is predicted using admetSAR, a free tool for evaluating chemical ADMET properties. (23092397)

Spectra

Mass Spec (NIST)

Download (11.4 KB)

Spectra

Spectrum	Spectrum Type	Splash Key
Predicted GC-MS Spectrum - GC-MS	Predicted GC-MS	Not Available
Mass Spectrum (Electron Ionization)	MS	splash10-0pb9-6392000000-a76f30f353b3407df0c6
Predicted MS/MS Spectrum - 10V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Positive (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 10V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 20V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
Predicted MS/MS Spectrum - 40V, Negative (Annotated)	Predicted LC-MS/MS	Not Available
LC-MS/MS Spectrum - LC-ESI-QTOF , positive	LC-MS/MS	splash10-0a4i-0090000000-3b46d60abcc8dfacf4d8
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-0udi-0019000000-71512d7a18cf60430dd9
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-0a4i-0092000000-e687a1e3760fb870dbc9
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-0a4i-0090000000-d450ded1f22039f00b63
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-0ab9-0190000000-e4211cbc2957a587e3d3
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-05fr-0590000000-51f4fa0445c2d047ef6b
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-0g4j-1960000000-a89e1c91bfa7b974be48
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-014j-4920000000-93c0877b3acf519d2b98
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-016u-7900000000-bc29714be08b6ae4120b
LC-MS/MS Spectrum - LC-ESI-QFT , positive	LC-MS/MS	splash10-0hi6-9600000000-7c6a3974d95a0015757e

Targets

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Details1. GABA(A) Receptor (Protein Group)

Kind

Protein group

Organism

Humans

Pharmacological action

Yes

Actions

Positive allosteric modulator

Curator comments

The GABA(A) receptor is pentameric (i.e. comprising 5 subunit proteins) and therefore has a multitude of potential isoforms. The above target is a collection of all possible GABA(A) subunits that may participate in the formation of the pentameric receptor and is not meant to imply direct a drug-protein interaction for each individual subunit.

General Function

Inhibitory extracellular ligand-gated ion channel activity

Specific Function

Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine...

---

Components:

Name	UniProt ID
Gamma-aminobutyric acid receptor subunit alpha-1	P14867
Gamma-aminobutyric acid receptor subunit alpha-2	P47869
Gamma-aminobutyric acid receptor subunit alpha-3	P34903
Gamma-aminobutyric acid receptor subunit alpha-4	P48169
Gamma-aminobutyric acid receptor subunit alpha-5	P31644
Gamma-aminobutyric acid receptor subunit alpha-6	Q16445
Gamma-aminobutyric acid receptor subunit beta-1	P18505
Gamma-aminobutyric acid receptor subunit beta-2	P47870
Gamma-aminobutyric acid receptor subunit beta-3	P28472
Gamma-aminobutyric acid receptor subunit delta	O14764
Gamma-aminobutyric acid receptor subunit epsilon	P78334
Gamma-aminobutyric acid receptor subunit gamma-1	Q8N1C3
Gamma-aminobutyric acid receptor subunit gamma-2	P18507
Gamma-aminobutyric acid receptor subunit gamma-3	Q99928
Gamma-aminobutyric acid receptor subunit pi	O00591
Gamma-aminobutyric acid receptor subunit theta	Q9UN88

References

1. Mohler H, Fritschy JM, Rudolph U: A new benzodiazepine pharmacology. J Pharmacol Exp Ther. 2002 Jan;300(1):2-8. [Article]
2. Riss J, Cloyd J, Gates J, Collins S: Benzodiazepines in epilepsy: pharmacology and pharmacokinetics. Acta Neurol Scand. 2008 Aug;118(2):69-86. doi: 10.1111/j.1600-0404.2008.01004.x. Epub 2008 Mar 31. [Article]

Details2. GABA(A) Receptor Benzodiazepine Binding Site (Protein Group)

Kind

Protein group

Organism

Humans

Pharmacological action

Yes

Actions

Ligand

Curator comments

Benzodiazepines modulate GABA(A) function by binding at the interface between alpha (α) and gamma (γ) subunits. Of the 6 α-subunits, only 4 (α-1, -2, -3, and -5) participate in the formation of this binding site. The above target is a collection of all α- and γ-subunits that are known to participate in the formation of the benzodiazepine binding site.

General Function

Inhibitory extracellular ligand-gated ion channel activity

Specific Function

Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine...

---

Components:

Name	UniProt ID
Gamma-aminobutyric acid receptor subunit alpha-1	P14867
Gamma-aminobutyric acid receptor subunit alpha-2	P47869
Gamma-aminobutyric acid receptor subunit alpha-3	P34903
Gamma-aminobutyric acid receptor subunit alpha-5	P31644
Gamma-aminobutyric acid receptor subunit gamma-1	Q8N1C3
Gamma-aminobutyric acid receptor subunit gamma-2	P18507
Gamma-aminobutyric acid receptor subunit gamma-3	Q99928

References

1. Sigel E, Steinmann ME: Structure, function, and modulation of GABA(A) receptors. J Biol Chem. 2012 Nov 23;287(48):40224-31. doi: 10.1074/jbc.R112.386664. Epub 2012 Oct 4. [Article]
2. Zhu S, Noviello CM, Teng J, Walsh RM Jr, Kim JJ, Hibbs RE: Structure of a human synaptic GABAA receptor. Nature. 2018 Jul;559(7712):67-72. doi: 10.1038/s41586-018-0255-3. Epub 2018 Jun 27. [Article]

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Drug created at June 13, 2005 13:24 / Updated at September 21, 2023 08:43