Oxcarbazepine
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| Systematic (IUPAC) name |
| 10,11-dihydro- 10-oxo- 5H-dibenz(b,f)azepine- 5-carboxamide |
| Clinical data |
| Trade names |
Trileptal |
| AHFS/Drugs.com |
monograph |
| MedlinePlus |
a601245 |
| Pregnancy cat. |
C (US) |
| Legal status |
POM (UK) ℞-only (US) |
| Routes |
Oral (Tablets or Suspension) |
| Pharmacokinetic data |
| Bioavailability |
> 95% |
| Protein binding |
? |
| Metabolism |
Hepatic
(Cytosolic Enzymes & Glucuronic Acid) |
| Half-life |
1–5 hours (healthy adults) |
| Excretion |
Renal |
| Identifiers |
| CAS number |
28721-07-5 Y |
| ATC code |
N03AF02 |
| PubChem |
CID 34312 |
| DrugBank |
DB00776 |
| ChemSpider |
31608 Y |
| UNII |
VZI5B1W380 Y |
| KEGG |
D00533 Y |
| ChEMBL |
CHEMBL1068 Y |
| Chemical data |
| Formula |
C15H12N2O2 |
| Mol. mass |
252.268 g/mol |
SMILES
- O=C3c1c(cccc1)N(c2ccccc2C3)C(=O)N
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InChI
-
InChI=1S/C15H12N2O2/c16-15(19)17-12-7-3-1-5-10(12)9-14(18)11-6-2-4-8-13(11)17/h1-8H,9H2,(H2,16,19) Y
Key:CTRLABGOLIVAIY-UHFFFAOYSA-N Y
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| Y (what is this?) (verify) |
Oxcarbazepine // is an anticonvulsant and mood-stabilizing drug, used primarily in the treatment of epilepsy. It is also used to treat anxiety and mood disorders, and benign motor tics. Oxcarbazepine is marketed as Trileptal by Novartis and available in some countries as a generic drug.
Contents
- 1 Uses
- 2 Structure pharmacology
- 3 History
- 4 Side effects
- 5 Possible reproductive risks
- 6 References
- 7 External links
Uses[edit]
In treatment of epilepsy, oxcarbazepine has recently been found to be associated with a greater enhancement in mood and reduction in anxiety symptoms than other drugs employed to treat epilepsy.[1]
It also appears to be effective in approximately half of patients with bipolar disorder and is well tolerated.[2]
Structure pharmacology[edit]
Oxcarbazepine is a structural derivative of carbamazepine, with a ketone in place of the carbon–carbon double bond on the dibenzazepine ring at the 10 position (10-keto). This difference helps reduce the impact on the liver of metabolizing the drug, and also prevents the serious forms of anemia or agranulocytosis occasionally associated with carbamazepine. Aside from this reduction in side effects, it is thought to have the same mechanism as carbamazepine – sodium channel inhibition (presumed to be the main mechanism of action) – and is generally used to treat the same conditions.
Oxcarbazepine is a prodrug which is activated to eslicarbazepine in the liver.[3]
History[edit]
First synthesized in 1965,[citation needed] it was patent-protected by Geigy in 1969 through DE 2011087 . It was approved for use as an anticonvulsant in Denmark in 1990, Spain in 1993, Portugal in 1997, and eventually for all other EU countries in 1999. It was approved in the US in 2000. In September 2010, Novartis pled guilty to marketing Trileptal for the unapproved uses of neuropathic pain and bipolar disorder during 2000 and 2001.[4]
Side effects[edit]
Oxcarbazepine can cause dizziness, drowsiness, blurred or double vision, fatigue, and may cause headaches, nausea and vomiting. There is also evidence of difficulty in concentration and mental sluggishness. It can also cause hyponatremia (2.7% of patients), so blood sodium levels should be tested if the patient complains of severe fatigue. Some of these side effects (such as headache) are more pronounced shortly after a dose is taken and tend to fade with the passage of time (generally 60 to 90 minutes). A craving for salty foods (such as potato chips) and increased impulsiveness have also been noted. Other side effects include stomach pain, tremor, rash, diarrhea, constipation, decreased appetite and dry mouth. Skin sensitivity to sunlight also may increase, and patients could experience severe sunburns as a result of sun exposure. The frequency of adverse effects rises above a daily dosage of 1200 mg. Some patients reported a sensation of incontinence without cause after taking the drug.
Possible reproductive risks[edit]
Oxcarbazapine may cause oral hormonal contraceptives to be less effective.
Increased incidences of fetal structural abnormalities and other manifestations of developmental toxicity (embryolethality, growth retardation) were observed in the offspring of animals (rats and rabbits) treated with either oxcarbazepine or its active 10-hydroxy metabolite (MHD) during pregnancy at doses similar to the maximum recommended human dose.
There are no adequate and well-controlled clinical studies of oxcarbazepine in pregnant women; however, oxcarbazepine is closely related structurally to carbamazepine, which is considered to be teratogenic in humans. Given this fact, and the results of the animal studies described, it is likely that oxcarbazepine is a human teratogen. Oxcarbazepine should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
Nursing mothers[edit]
Oxcarbazepine and its active metabolite MHD are excreted in human breast milk. Because of the potential for serious adverse reactions to oxcarbazepine in nursing infants, a decision should be made about whether to discontinue nursing or to discontinue the drug in nursing women.
References[edit]
- ^ Mazza M, Della Marca G, Di Nicola M, et al. (May 2007). "Oxcarbazepine improves mood in patients with epilepsy". Epilepsy Behav 10 (3): 397–401. doi:10.1016/j.yebeh.2007.01.003. PMID 17300991.
- ^ Ghaemi SN, Berv DA, Klugman J, Rosenquist KJ, Hsu DJ (August 2003). "Oxcarbazepine treatment of bipolar disorder". J Clin Psychiatry 64 (8): 943–5. doi:10.4088/JCP.v64n0813. PMID 12927010.
- ^ Dulsat, C., Mealy, N., Castaner, R., Bolos, J. (2009). "Eslicarbazepine acetate". Drugs of the Future 34 (3): 189. doi:10.1358/dof.2009.034.03.1352675.
- ^ U.S. District Court for the Eastern District of Pennsylvania. "Government’s memorandum for entry of plea and sentencing".
- ChemicalLand21.com: Oxcarbazepine
- Trileptal StoryDead Link
- Trileptal.com(Novartis)
- Prescribing Information(PDF)
- psychatlanta.com
External links[edit]
- RxList entry
- http://www.psycheducation.org/depression/meds/moodstabilizers.htm
- http://www.psycheducation.org/depression/meds/trileptal.htm
- DrugBank entry
- http://www.konduskarlabs.com
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Anticonvulsants (N03)
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| GABAA receptor agonist |
|
Barbiturates
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- Barbexaclone
- Metharbital
- Methylphenobarbital
- Pentobarbital
- Phenobarbital#
- Primidone
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|
|
Benzodiazepines
|
- Clobazam
- Clonazepam
- Clorazepate
- Diazepam#
- Flutoprazepam
- Lorazepam
- Midazolam
- Nimetazepam
- Nitrazepam
- Temazepam
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| Other GABA agents |
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Aromatic allylic alcohols
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| Carbonic anhydrase inhibitor |
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Sulfa drugs
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- Acetazolamide
- Ethoxzolamide
- Sultiame
- Zonisamide
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| Channel blockers |
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Primarily sodium
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Hydantoins
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- Ethotoin
- Fosphenytoin
- Mephenytoin
- Phenytoin#
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Carboxamides
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- Carbamazepine#
- Eslicarbazepine acetate
- Oxcarbazepine
- Oxitriptyline
- Rufinamide
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Primarily calcium
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Succinimides
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- Ethosuximide#
- Mesuximide
- Phensuximide
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AMPA receptor
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Unknown/ungrouped
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- Phenyltriazine (Lamotrigine), Oxazolidinediones (Ethadione
- Paramethadione
- Trimethadione), Ureas (Phenacemide
- Pheneturide), Monosaccharide (Topiramate)
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| Channel openers |
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| Indirect GABA agents |
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Carboxylic acids/
Fatty acid derivatives
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- GABA transaminase inhibitor: Valproic acid# (Sodium valproate & Valproate semisodium)
- Valpromide
- Valnoctamide
- Valproate pivoxil
GABA reuptake inhibitor: Tiagabine
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GABA analogs
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- Gabapentin
- Pregabalin
- Progabide
- Tolgabide
- Vigabatrin
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Unknown/multiple/
unsorted |
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Carbamates/sulfamates
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- Carisbamate†
- Emylcamate
- Felbamate
- JNJ-26990990§
- Meprobamate
- Topiramate
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Pyrrolidines
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- Brivaracetam
- Levetiracetam
- Nefiracetam
- Seletracetam
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Propionates
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Aldehydes
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Bromides
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- Potassium bromide
- Sodium bromide
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- #WHO-EM
- ‡Withdrawn from market
- Clinical trials:
- †Phase III
- §Never to phase III
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anat (n/s/m/p/4/e/b/d/c/a/f/l/g)/phys/devp
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noco (m/d/e/h/v/s)/cong/tumr, sysi/epon, injr
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proc, drug (N1A/2AB/C/3/4/7A/B/C/D)
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Mood stabilizers
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- Carbamazepine
- Divalproex sodium
- Gabapentin
- Lamotrigine
- Licarbazepine
- Lithium
- Oxcarbazepine
- Pregabalin
- Sodium valproate
- Tiagabine
- Topiramate
- Valproic acid
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Mood disorder (F30–F39, 296)
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| History |
- Emil Kraepelin
- Karl Leonhard
- John Cade
- Mogens Schou
- Frederick K. Goodwin
- Kay Redfield Jamison
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| Symptoms |
- Hallucination
- Delusion
- Emotional dysregulation
- Anhedonia
- Dysphoria
- Suicidal ideation
- sleep disorder
- Psychosis
- Racing thoughts
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| Spectrum |
- Bipolar disorder
- Bipolar I
- Bipolar II
- Bipolar NOS
- Cyclothymia
- Dysthymia
- Major depressive disorder
- Schizoaffective disorder
- Mania
- Mixed state
- Hypomania
- Major depressive episode
- Rapid cycling
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| Treatment |
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Anticonvulsants
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- Carbamazepine
- Gabapentin
- Lamotrigine
- Oxcarbazepine
- Topiramate
- Valproic acid
- Sodium valproate
- Valproate semisodium
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Other mood stabilizers
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- Lithium
- Lithium carbonate
- Lithium citrate
- Lithium sulfate
- Antipsychotics
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Non-pharmaceutical
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- Clinical psychology
- Electroconvulsive therapy
- Involuntary commitment
- Light therapy
- Psychotherapy
- Transcranial magnetic stimulation
- Cognitive behavioral therapy
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dsrd (o, p, m, p, a, d, s), sysi/epon, spvo
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proc (eval/thrp), drug (N5A/5B/5C/6A/6B/6D)
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