Oxcarbazepine

Bezeichnung:Oxcarbazepine

CAS-Nr28721-07-5

Englisch Name:Oxcarbazepine

CBNumberCB9238172

SummenformelC15H12N2O2

Molgewicht252.27

MOL-Datei28721-07-5.mol

Oxcarbazepine physikalisch-chemischer Eigenschaften

Schmelzpunkt	215-216°C
Siedepunkt	457.2±55.0 °C(Predicted)
Dichte	1.329±0.06 g/cm3(Predicted)
Flammpunkt	230.3±31.5 °C
storage temp.	Sealed in dry,Room Temperature
Löslichkeit	DMSO: ~9 mg/mL
Aggregatzustand	solid
pka	13.73±0.20(Predicted)
Farbe	white
Wasserlöslichkeit	Soluble in DMSO, methanol, water, ethanol and acetone.
Merck	14,6929
BCS Class	4
CAS Datenbank	28721-07-5(CAS DataBase Reference)
EPA chemische Informationen	5H-Dibenz[b,f]azepine-5-carboxamide, 10,11-dihydro-10-oxo- (28721-07-5)

Sicherheit

Kennzeichnung gefährlicher	Xn,F
R-Sätze:	22-36-20/21/22-11
S-Sätze:	16-36/37
RIDADR	UN 1648 3 / PGII
WGK Germany	3
RTECS-Nr.	HN8445000
HS Code	29339900
Giftige Stoffe Daten	28721-07-5(Hazardous Substances Data)

Gefahreninformationscode (GHS)

Oxcarbazepine Chemische Eigenschaften,Einsatz,Produktion Methoden

Beschreibung
Oxcarbazepine is a new antiepileptic carbamazepine derivative, reportedly better tolerated than carbamazepine. It appears to be most effective in partial epilepsy with complex seizures.
Chemische Eigenschaften
Pale Yellow Powder
Originator
Ciba-Geigy (Switzerland)
Verwenden
beta-adrenergic blocker
Verwenden
A metabolite of Eslicarbazepine acetate, (BIA 2-093), a novel central nervous system drug.
Verwenden
The keto derivative of Carbamazepine. Used as an anticonvulsant
Verwenden
Oxcarbazepine is a sodium channel protein inhibitor. It is an anticonvulsant and mood-stab.
Definition
ChEBI: A dibenzoazepine derivative, having a carbamoyl group at the ring nitrogen, substituted with an oxo group at C-4 of the azepeine ring which is also hydrogenated at C-4 and C-5. It is a anticholinergic anticonvulsant and mood stabilizing drug, used primaril in the treatment of epilepsy.
Trademarks
Trileptal (Novartis).
Biologische Funktion
Oxcarbazepine is chemically and pharmacologically closely related to carbamazepine, but it has much less capacity to induce drug-metabolizing enzymes. This property decreases the problems associated with drug interactions when oxcarbazepine is used in combination with other drugs. The clinical uses and adverse effect profile of oxcarbazepine appear to be similar to those of carbamazepine.
Allgemeine Beschreibung
Oxcarbazepine, marketed under the trade name Trileptal^?, is an anticonvulsant developed and prescribed for treatment of epilepsy. In recent years, Oxcarbazepine has shown efficacy in treatment of mood disorders. This certified solution standard is suitable as starting material for the preparation of calibrators and controls in oxcarbazepine testing by GC/MS or LC-MS/MS.
Biologische Aktivität
Anticonvulsant; protects mice and rats against generalized tonic-clonic seizures induced by electroshock. Thought to act via inhibition of sodium channel activity.
Biochem/physiol Actions
Anticonvulsant, antineuralgic. Inhibits veratrine-induced transmitter release.
Mechanism of action
Although oxcarbazepine is less potent that CBZ, its mechanism of action is similar. The majority of the pharmacological activity for oxcarbazepine is attributed to its primary metabolite, 10-monohydroxycarbazepine (MHD), the plasma levels of which may be ninefold higher than those for CBZ. Both oxcarbazepine and MHD produce a blockade of voltagedependent sodium channels, thus decreasing repetitive firing and spread of electrical activity. An additional action on calcium and potassium channels may contribute to the therapeutic effect. Like carbamazepine, oxcarbazepine may worsen juvenile myoclonic or absence seizures.
Pharmakokinetik
Oxcarbazepine is completely absorbed, and food has no effect on its absorption. Unlike CBZ, it does not cause autoinduction of its own metabolism. The metabolism of oxcarbazepine is different from that of CBZ. Oxcarbazepine is reduced by cytosolic enzymes to MHD before its O-glucuronidation. More than 95% of its oral dose is excreted as conjugated metabolites, with approximately 4% of the drug converted to inactive 10,11-dihydroxy CBZ. Unlike CBZ, no epoxide nor aromatic hydroxylation metabolites are formed. The half-life is 2 hours for oxcarbazepine and 9 hours for the active 10-monohydroxy metabolite. In patients with impaired renal function, the half-life for MHD is prolonged to 19 hours, with a doubling in its area under the plasma concentration curve. Peak plasma concentration following an oral dose occurs at approximately 4.5 hours.
Oxcarbazepine induces CYP3A4/5 and UTP, and it also inhibits CYP2C19, producing significant effects on the plasma concentration of other drugs. Therefore, oxcarbazepine decreases felodipine bioavailability and lowers plasma levels for lamotrigine, CBZ, CBZ epoxide, calcium channel blockers, and oral contraceptives. Oxcarbazepine increases plasma levels of phenobarbital and phenytoin. Unlike carbamazepine, oxcarbazepine has no effect on plasma levels of risperidone or olanzepine. The plasma levels for oxcarbazepine or MHD are decreased by CBZ, phenobarbital, phenytoin, valproate, and verapamil. Serum MHD may decrease during pregnancy but increase following delivery. Oxcarbazepine clearance is decreased in renal impairment and the elderly. In children, a higher dose/kg for oxcarbazepine than in adults is required to obtain an effective plasma concentration.
Clinical Use
Oxcarbazepine (Trileptal?) is the 10-keto analogue of carbamazepine. It is indicated as monotherapy or adjunctive therapy for partial seizures in adults with epilepsy, as monotherapy for the treatment of partial seizures in children 4 years of age or older, and as adjunct therapy in children 2 to 4 years of age.
Nebenwirkungen
Patients with hypersensitivity reactions to carbamazepine can be expected to show cross-sensitivity (e.g., rash) or related problems to oxcarbazepine. The improved toxicity profile for oxcarbazepine when compared to CBZ may result from absence of the epoxide or CBZ-iminoquinone metabolites. The most common side effects are headache, dizziness, nystagmus, blurred vision, somnolence, nausea, ataxia, and fatigue. The incidence of adverse effects has been related to elevated serum MHD concentrations. Adverse effects on cognitive status, hyponatremia, and serious dermatological reactions have been reported, as has hyponatremia.
Synthese
Oxcarbazepine can be obtained in two different ways.
1) Reaction of 10-methoxy-5H-dibenz[b,f]azepine (1) with phosgene gives the 5- chlorocarbonyl compound, treatment with NH3 affords 10-methoxy-5H-dibenz[b,f ]azepine-5-carboxamide (2), which is hydrolyzed with diluted HCl to oxcarbazepine.
2) Nitration of 5-cyano-5H-dibenz[b,f ]azepine (3) with NaNO3 in acetic anhydride/acetic acid gives 5-cyano-10-nitro-5H-dibenz[b,f ]azepine (4), which is treated with BF3 and powdered iron in acetic acid.
Arzneimittelwechselwirkung
Potentially hazardous interactions with other drugs
Antidepressants: antagonism of anticonvulsant effect; avoid with St John’s wort.
Antiepileptics: concentration of perampanel reduced, also increased oxcarbazepine concentration.
Antimalarials: anticonvulsant effect antagonised by mefloquine.
Antipsychotics: antagonism of anticonvulsant effect.
Antivirals: concentration of rilpivirine and possibly daclatasvir and simeprevir reduced - avoid; possibly reduces dolutegravir concentration.
Ciclosporin: metabolism accelerated (reduced ciclosporin concentration).
Clopidogrel: possibly reduced antiplatelet effect.
Cytotoxics: concentration of imatinib reduced - avoid.
Guanfacine: possibly reduces guanfacine concentration - increase dose of guanfacine.
Oestrogens and progestogens: metabolism accelerated (reduced contraceptive effect).
Orlistat: possible increased risk of convulsions.
Tacrolimus: metabolism accelerated (reduced tacrolimus concentration).
Ulipristal: possibly reduces contraceptive effect.
Stoffwechsel
Oxcarbazepine is rapidly reduced by cytosolic enzymes in the liver to the active monohydroxy metabolite (licarbezine, or MHD). MHD is metabolised further by conjugation with glucuronic acid.
Minor amounts (4% of the dose) are oxidised to a pharmacologically inactive metabolite. Oxcarbazepine is excreted in the urine mainly as metabolites.
Lager
Store at RT

Oxcarbazepine Upstream-Materialien And Downstream Produkte

Oxcarbazepine Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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