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Details

Stereochemistry ACHIRAL
Molecular Formula C15H12N2O.2H2O
Molecular Weight 272.2991
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of CARBAMAZEPINE DIHYDRATE

SMILES

O.O.NC(=O)N1C2=CC=CC=C2C=CC3=CC=CC=C13

InChI

InChIKey=UPTJXAHTRRBMJE-UHFFFAOYSA-N
InChI=1S/C15H12N2O.2H2O/c16-15(18)17-13-7-3-1-5-11(13)9-10-12-6-2-4-8-14(12)17;;/h1-10H,(H2,16,18);2*1H2

HIDE SMILES / InChI

Description
Curator's Comment: description was created based on several sources, including: https://www.drugs.com/carbamazepine.html http://www.rxlist.com/carnexiv-drug.htm http://www.wikidoc.org/index.php/Carbamazepine

Carbamazepine is an analgesic, anti-epileptic agent that is FDA approved for the treatment of epilepsy, trigeminal neuralgia. It appears to act by reducing polysynaptic responses and blocking the post-tetanic potentiation. It depresses thalamic potential and bulbar and polysynaptic reflexes, including the linguomandibular reflex in cats. Commonly reported side effects of carbamazepine include: dizziness, drowsiness, nausea, ataxia, and vomiting. Carbamazepine is a potent inducer of hepatic CYP1A2, 2B6, 2C9/19, and 3A4 and may reduce plasma concentrations of concomitant medications mainly metabolized by CYP1A2, 2B6, 2C9/19, and 3A4 through induction of their metabolism, like Boceprevir, Cyclophosphamide, Aripiprazole, Tacrolimus, Temsirolimus and others.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
152.0 µM [IC50]
25.0 µM [Ki]
Target ID: Q9NY46|||Q9Y6P4
Gene ID: 6328.0
Gene Symbol: SCN3A
Target Organism: Homo sapiens (Human)
16.0 µM [EC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
TEGRETOL

Approved Use

Epilepsy Carbamazepine is indicated for use as an anticonvulsant drug. Evidence supporting efficacy of carbamazepine as an anticonvulsant was derived from active drug-controlled studies that enrolled patients with the following seizure types: 1. Partial seizures with complex symptomatology (psychomotor, temporal lobe). Patients with these seizures appear to show greater improvement than those with other types. 2. Generalized tonic-clonic seizures (grand mal). 3. Mixed seizure patterns which include the above, or other partial or generalized seizures. Absence seizures (petit mal) do not appear to be controlled by carbamazepine (see PRECAUTIONS, General). Trigeminal Neuralgia Carbamazepine is indicated in the treatment of the pain associated with true trigeminal neuralgia. Beneficial results have also been reported in glossopharyngeal neuralgia. This drug is not a simple analgesic and should not be used for the relief of trivial aches or pains.

Launch Date

1968
Primary
TEGRETOL

Approved Use

Epilepsy Carbamazepine is indicated for use as an anticonvulsant drug. Evidence supporting efficacy of carbamazepine as an anticonvulsant was derived from active drug-controlled studies that enrolled patients with the following seizure types: 1. Partial seizures with complex symptomatology (psychomotor, temporal lobe). Patients with these seizures appear to show greater improvement than those with other types. 2. Generalized tonic-clonic seizures (grand mal). 3. Mixed seizure patterns which include the above, or other partial or generalized seizures. Absence seizures (petit mal) do not appear to be controlled by carbamazepine (see PRECAUTIONS, General). Trigeminal Neuralgia Carbamazepine is indicated in the treatment of the pain associated with true trigeminal neuralgia. Beneficial results have also been reported in glossopharyngeal neuralgia. This drug is not a simple analgesic and should not be used for the relief of trivial aches or pains.

Launch Date

1968
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
3.2 μg/mL
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CARBAMAZEPINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: FASTED
1.9 μg/mL
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CARBAMAZEPINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
11 μg/mL
800 mg 2 times / day multiple, oral
dose: 800 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
CARBAMAZEPINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
4.3 μg/mL
400 mg single, oral
dose: 400 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CARBAMAZEPINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: HIGH-FAT
3.2 μg/mL
1600 mg 1 times / day multiple, oral
dose: 1600 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
CARBAMAZEPINE-10,11-EPOXIDE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
1.5 μg/mL
800 mg 1 times / day multiple, oral
dose: 800 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
CARBAMAZEPINE-10,11-EPOXIDE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
0.11 μg/mL
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CARBAMAZEPINE-10,11-EPOXIDE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
2.2 μg/mL
800 mg 2 times / day multiple, oral
dose: 800 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
CARBAMAZEPINE-10,11-EPOXIDE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
AUC

AUC

ValueDoseCo-administeredAnalytePopulation
32.6 μg × h/mL
1600 mg 1 times / day multiple, oral
dose: 1600 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
CARBAMAZEPINE-10,11-EPOXIDE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
15.7 μg × h/mL
800 mg 1 times / day multiple, oral
dose: 800 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
CARBAMAZEPINE-10,11-EPOXIDE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
37.5 h
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CARBAMAZEPINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
14.5 h
800 mg 2 times / day multiple, oral
dose: 800 mg
route of administration: Oral
experiment type: MULTIPLE
co-administered:
CARBAMAZEPINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
34 h
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CARBAMAZEPINE-10,11-EPOXIDE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
24%
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CARBAMAZEPINE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
50%
200 mg single, oral
dose: 200 mg
route of administration: Oral
experiment type: SINGLE
co-administered:
CARBAMAZEPINE-10,11-EPOXIDE plasma
Homo sapiens
population: UNKNOWN
age: UNKNOWN
sex: UNKNOWN
food status: UNKNOWN
Doses

Doses

DosePopulationAdverse events​
1000 mg 2 times / day multiple, oral
Highest studied dose
Dose: 1000 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1000 mg, 2 times / day
Sources: Page: p.1297
unhealthy, 73.1 ± 5.5
n = 91
Health Status: unhealthy
Condition: Epilepsy
Age Group: 73.1 ± 5.5
Sex: M+F
Population Size: 91
Sources: Page: p.1297
Disc. AE: Skin and subcutaneous conditions NEC, Fatigue...
AEs leading to
discontinuation/dose reduction:
Skin and subcutaneous conditions NEC (8.8%)
Fatigue
Somnolence
Sources: Page: p.1297
AEs

AEs

AESignificanceDosePopulation
Skin and subcutaneous conditions NEC 8.8%
Disc. AE
1000 mg 2 times / day multiple, oral
Highest studied dose
Dose: 1000 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1000 mg, 2 times / day
Sources: Page: p.1297
unhealthy, 73.1 ± 5.5
n = 91
Health Status: unhealthy
Condition: Epilepsy
Age Group: 73.1 ± 5.5
Sex: M+F
Population Size: 91
Sources: Page: p.1297
Fatigue Disc. AE
1000 mg 2 times / day multiple, oral
Highest studied dose
Dose: 1000 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1000 mg, 2 times / day
Sources: Page: p.1297
unhealthy, 73.1 ± 5.5
n = 91
Health Status: unhealthy
Condition: Epilepsy
Age Group: 73.1 ± 5.5
Sex: M+F
Population Size: 91
Sources: Page: p.1297
Somnolence Disc. AE
1000 mg 2 times / day multiple, oral
Highest studied dose
Dose: 1000 mg, 2 times / day
Route: oral
Route: multiple
Dose: 1000 mg, 2 times / day
Sources: Page: p.1297
unhealthy, 73.1 ± 5.5
n = 91
Health Status: unhealthy
Condition: Epilepsy
Age Group: 73.1 ± 5.5
Sex: M+F
Population Size: 91
Sources: Page: p.1297
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG



Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
strong
yes (co-administration study)
Comment: Midazolam plasma concentrations reduced dramatically in patients treated with carbamazepine and phenytoin; The CYP3A4-mediated metabolism of cyclosporin is markedly accelerated by carbamazepine comedication; Many other likely DDIs with carbamazepine. See https://pubmed.ncbi.nlm.nih.gov/8877250/
Page: 12.0
yes
yes
yes
yes
Drug as victimTox targets

Tox targets

TargetModalityActivityMetaboliteClinical evidence
PubMed

PubMed

TitleDatePubMed
A common mutation in the methylenetetrahydrofolate reductase gene is a determinant of hyperhomocysteinemia in epileptic patients receiving anticonvulsants.
1999 Aug
Effects of the calcium antagonists verapamil and nitrendipine on carbamazepine withdrawal.
1999 Dec
[Carbamazepine induced hyponatremia].
1999 Jan
Potential fluconazole-induced carbamazepine toxicity.
1999 Jul-Aug
A reporter gene assay to assess the molecular mechanisms of xenobiotic-dependent induction of the human CYP3A4 gene in vitro.
1999 Mar
Carbamazepine-induced hepatorenal failure in a child.
1999 May
Epileptic negative myoclonus induced by carbamazepine in a child with BECTS. Benign childhood epilepsy with centrotemporal spikes.
1999 Sep
Carbamazepine-associated severe left ventricular dysfunction.
2000
Worsening of symptoms of multiple sclerosis associated with carbamazepine.
2000 Apr 22
Sodium valproate inhibits production of TNF-alpha and IL-6 and activation of NF-kappaB.
2000 Feb 28
Phenytoin poisoning after using Chinese proprietary medicines.
2000 Jul
Potential interaction between ritonavir and carbamazepine.
2000 Jul
Block of rat brain recombinant SK channels by tricyclic antidepressants and related compounds.
2000 Jul 28
[A case of superior sagittal sinus thrombosis following long-term medication with carbamazepine].
2000 Jun
Color vision in epilepsy patients treated with vigabatrin or carbamazepine monotherapy.
2000 May
[Carbamazepine-induced hepatitis].
2000 Oct 10
Novel treatments for bipolar disorder.
2001 Apr
Comparison the cognitive effect of anti-epileptic drugs in seizure-free children with epilepsy before and after drug withdrawal.
2001 Apr
Illness characteristics and their association with prescription patterns for bipolar I disorder.
2001 Feb
Antiepileptic drug withdrawal in patients with temporal lobe epilepsy undergoing presurgical video-EEG monitoring.
2001 Feb
The influence of food on the bioavailability of a twice-daily controlled release carbamazepine formulation.
2001 Feb
Rufinamide: a double-blind, placebo-controlled proof of principle trial in patients with epilepsy.
2001 Feb
The response of neuropathic pain and pain in complex regional pain syndrome I to carbamazepine and sustained-release morphine in patients pretreated with spinal cord stimulation: a double-blinded randomized study.
2001 Feb
Independent short-term variability of spike-like (600 Hz) and postsynaptic (N20) cerebral SEP components.
2001 Feb 12
A model of atypical absence seizures: EEG, pharmacology, and developmental characterization.
2001 Feb 13
[Maintenance dose requirement for phenytoin is lowered in genetically impaired drug metabolism independent of concommitant use of other antiepileptics].
2001 Feb 17
Determination of drug residues in water by the combination of liquid chromatography or capillary electrophoresis with electrospray mass spectrometry.
2001 Feb 23
[Carbamazepine-induced SIADH with clinical signs of delirium].
2001 Jan
Relief of cluster headache and cranial neuralgias. Promising prophylactic and symptomatic treatments.
2001 Jan
Ritonavir-induced carbamazepine toxicity.
2001 Jan
Acute intermittent porphyria, seizures, and antiepileptic drugs: a report on a 3-year-old Nigerian boy.
2001 Jan
Effects of antiepileptic drugs on rat platelet aggregation: ex vivo and in vitro study.
2001 Jan
[Klüver-Bucy syndrome in herpetic meningoencephalitis].
2001 Jan 27
Mood stabilizers and ion regulation.
2001 Jan-Feb
Taking the sting out of trigeminal neuralgia.
2001 Mar
Influence of retigabine on the anticonvulsant activity of some antiepileptic drugs against audiogenic seizures in DBA/2 mice.
2001 Mar
Association of human herpesvirus 6 infection with drug reaction with eosinophilia and systemic symptoms.
2001 Mar
Carbamazepine prevents imipramine-induced behavioural sensitization to the dopamine D(2)-like receptor agonist quinpirole.
2001 Mar 23
Patents

Sample Use Guides

In Vivo Use Guide
Curator's Comment: The total daily dose of CARNEXIV is 70% of the total daily oral carbamazepine dose from which patients are being switched. The total daily dose of CARNEXIV should be equally divided in four 30-minute infusions, separated by 6 hours.
Initial Dose: 400 mg per day. Subsequent Dose: add up to 200 mg per day at weekly intervals. Maximum daily dose is 1600 mg
Route of Administration: Other
Human liver microsomes (HLMs) converted carbamazepine (30-300 microM) to 3-hydroxycarbamazepine at rates >25 times those of 2-hydroxycarbamazepine. Rates of carbamazepine 2- and 3-hydroxylation correlated strongly with CYP2B6 activity (r >or= 0.757) in a panel of HLMs (n = 8). Carbamazepine 3-hydroxylation also correlated significantly with CYP2C8 activity at a carbamazepine concentration of 30 microM.
Name Type Language
CARBAMAZEPINE DIHYDRATE
Common Name English
5H-DIBENZ(B,F)AZEPINE-5-CARBOXAMIDE, HYDRATE (1:2)
Systematic Name English
Code System Code Type Description
PUBCHEM
158856
Created by admin on Fri Dec 15 19:17:47 GMT 2023 , Edited by admin on Fri Dec 15 19:17:47 GMT 2023
PRIMARY
CAS
85756-57-6
Created by admin on Fri Dec 15 19:17:47 GMT 2023 , Edited by admin on Fri Dec 15 19:17:47 GMT 2023
PRIMARY
EPA CompTox
DTXSID00235052
Created by admin on Fri Dec 15 19:17:47 GMT 2023 , Edited by admin on Fri Dec 15 19:17:47 GMT 2023
PRIMARY
FDA UNII
78M1RMW7Q8
Created by admin on Fri Dec 15 19:17:47 GMT 2023 , Edited by admin on Fri Dec 15 19:17:47 GMT 2023
PRIMARY