Brivaracetam

Gefahreninformationscode (GHS)

• Bildanzeige (GHS)

  

• Alarmwort

  Warnung

• Gefahrenhinweise

  H302：Gesundheitsschädlich bei Verschlucken.

• Sicherheit

  P264：Nach Gebrauch gründlich waschen.

  P264：Nach Gebrauch gründlich waschen.

  P270：Bei Gebrauch nicht essen, trinken oder rauchen.

  P301+P312：BEI VERSCHLUCKEN: Bei Unwohlsein GIFTINFORMATIONSZENTRUM/Arzt/... (geeignete Stelle für medizinische Notfallversorgung vom Hersteller/Lieferanten anzugeben) anrufen.

  P330：Mund ausspülen.

  P501：Inhalt/Behälter ... (Entsorgungsvorschriften vom Hersteller anzugeben) zuführen.

Brivaracetam Chemische Eigenschaften,Einsatz,Produktion Methoden

• Beschreibung

  Brivaracetam, a novel oral antiepileptic drug with a high affinity for synaptic vesicle protein 2A (SV2A), was approved in Europe and the US as an adjunctive therapy for the treatment of partial onset seizures with or without secondary generalization in patients aged 16 or older.42 Brivaracetam is very closely related to levetiracetam, an antiepileptic treatment whose immediate release formulation has been available in the United States as a generic drug since 2008, but whose extended release formulation is under patent protection until 2028. The two drugs, which were both developed by UCB Pharma, are structurally similar with brivaracetam having an n-propyl group at the C-4 position of the pyrrolidinone ring and levetiracetam having a hydrogen at this same position. A systematic investigation of the various substitutions of levetiracetam resulted in the identification of more potent and selective SV2A ligands and ultimately culminated in the discovery of brivaracetam, which has greater affinity for SV2A, improved selectivity, more rapid brain penetration, and faster onset of action against seizures than levetiracetam.

• Verwenden

  Treatment ofTreatment of epilepsy, neuropathic pain and essential tremor.

• Verwenden

  Brivaracetam, is a 4-n-propyl analog of levetiracetam (L331500), and a racetam derivative with anticonvulsant properties.

• Definition

  ChEBI: A non-proteinogenic amino acid derivative that is butanamide in which the pro-S hydrogen at position 2 is replaced by a (4R)-2-oxo-4-propylpyrrolidin-1-yl. Used for treatment of partial onset seizures related to epilepsy.

• Clinical Use

  Antiepileptic agent

• Nebenwirkungen

  Common side effects of brivaracetam include: constipation, nausea, vomiting, extreme tiredness or low energy. Serious side effects that may be caused include: swelling of the face, throat, tongue, lips, and eyes; difficulty swallowing or breathing; hoarseness, hallucinations (seeing things or hearing sounds that are not there), and delusions (strange thoughts or beliefs that have no basis in reality). An overdose may cause: drowsiness, extreme tiredness, dizziness, difficulty maintaining balance, blurred or double vision, slowed heartbeat, nausea, and feeling anxious.

• Synthese

  Two enantioselective routes have been reported, one employing an enzymatic resolution and the other utilizing (R)- (-)-epichlorohydrin as a chiral starting material. The route involves an enzymatic resolution, is the only kilogram-scale route disclosed in the literature to date and reportedly permits the production of brivaracetam within the required commercial quality specifications. However, the authors note that the development of this route for commercial purposes has been stopped. Commercial dimethyl n-propylmalonate 108 was first alkylated with tertbutyl- 2-bromoacetate. The resulting product underwent Krapcho decarboxylation to afford racemic succinate derivative 109 in 94% yield over the two steps. Optimized conditions for the key enzymatic resolution employed protease C from Bacillus subtilis type 2 at 30 ??C for 18 h to resolve ester 109 and provide the acid enantiomer 110. This biocatalytic process allowed for residual unreacted diester 109 to be washed away with cyclohexane at pH 9 (adjusted with 0.5 M NaOH), and the desired acid 110 could be isolated upon lowering the pH (??1) and extracting with isopropyl acetate (42% yield, 97% ee). The transformation of acid 110 into propyllactone 111 proceeded in nearly quantitative yield by a three-step sequence: activation of the acid with ethyl chloroformate, reduction to the alcohol with sodium borohydride, and cyclization upon acidic workup with TFA. Exposure of 111 to HBr in acetic acid followed by esterification of the resulting acid-generated bromoester 112. Finally, TBAI-catalyzed alkylation of 112 with commercial (S)-2-aminobutanamide (113) in refluxing isopropyl acetate introduced the n-butylamide moiety while facilitating lactamization. Addition of MTBE followed by filtration and recrystallization from isopropyl acetate afforded brivaracetam (IX) in 32% yield and 96% ee.

• Arzneimittelwechselwirkung

  Potentially hazardous interactions with other drugs
  Antibacterials: concentration reduced by rifampicin.
  Antidepressants: antagonism of anticonvulsant effect (convulsive threshold lowered).
  Antimalarials: mefloquine antagonises anticonvulsant effect.
  Antipsychotics: antagonism of anticonvulsant effect (convulsive threshold lowered).
  Orlistat: possibly increased risk of convulsions.

• Stoffwechsel

  Brivaracetam is mainly metabolised by hydrolysis of the amide moiety to form the corresponding carboxylic acid (approximately 60% the elimination), and secondarily by hydroxylation on the propyl side chain (approximately 30% the elimination). The hydrolysis of the amide moiety leading to the carboxylic acid metabolite (34% of the dose in urine) is supported by hepatic and extra-hepatic amidase. The metabolites are inactive. Greater than 95% of the dose is excreted in the urine as brivaracetam and its metabolites.

• Lager

  Store at -20°C

Brivaracetam Upstream-Materialien And Downstream Produkte

Brivaracetam Anbieter Lieferant Produzent Hersteller Vertrieb Händler.

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