Peringatan Keamanan

High doses of 2000 mg/kg/day in the mouse and rat and ?600 mg/kg/day in the dog were not well tolerated in animal studies. Seletracetam does not possess potential teratogenic, reproductive or embryonic toxicities. Most adverse effects are CNS-related effects, including somnolence, dizziness, feeling drunk, euphoria and nausea which all usually tend to be resolved within 24 hours.

Seletracetam

DB05885

small molecule investigational

Deskripsi

Seletracetam is a pyrrolidone derivative and with a structural similarity to newer generation antiepileptic drug levetiracetam. It binds to the same target as levetiracetam but with higher affinity and has shown potent seizure suppression in models of acquired and genetic epilepsy with high CNS tolerability. It is predicted to have low drug-drug interactions and inhibition or induction of any major human metabolizing enzymes. Seletracetam was in Phase II clinical trials under the supervision of the U.S. Food and Drug Administration (FDA) investigated as treatment of epilepsy and partial epilepsy however its development had been put on hold in July 2007. As of 2010, its production was further halted due to the investigation of a newer antiepileptic agent, brivaracetam.

Struktur Molekul 2D

Berat 232.2272
Wujud solid

Peta Jejaring Molekuler
Legenda: ObatTargetGenEnzim(Panah → menunjukkan arah efek / relasi)TransporterCarrier

Profil Farmakokinetik

Waktu Paruh (Half-Life) Approximately 8 hours in healthy young male subjects.
Volume Distribusi The volume of distribution is approximately 0.6 L/kg, which is close to that of total body water.
Klirens (Clearance) The total apparent clearance is approximately 0.8mL/min/kg.

Absorpsi

Seletracetam is rapidly absorbed following oral administration, reaching the Cmax within 1 hour and displaying oral bioavailability of >90%.

Metabolisme

It undergoes hydrolysis of the acetamide group to form the carboxylic acid metabolite ucb-101596-1, which is pharmacologically inactive.

Rute Eliminasi

Primarily eliminated through renal excretion. It is as mainly excreted as unchanged drug (30%) and an acidic metabolite ucb-101596-1 (60%).

Interaksi Obat

758 Data
Ceritinib Seletracetam may increase the bradycardic activities of Ceritinib.
Ivabradine Seletracetam may increase the bradycardic activities of Ivabradine.
Ruxolitinib Ruxolitinib may increase the bradycardic activities of Seletracetam.
Cimetidine The serum concentration of Seletracetam can be increased when it is combined with Cimetidine.
Clopidogrel The therapeutic efficacy of Clopidogrel can be decreased when used in combination with Seletracetam.
Efavirenz The serum concentration of Seletracetam can be decreased when it is combined with Efavirenz.
Melatonin The therapeutic efficacy of Seletracetam can be decreased when used in combination with Melatonin.
Nafcillin The therapeutic efficacy of Seletracetam can be decreased when used in combination with Nafcillin.
Nitroprusside Seletracetam may increase the hypotensive activities of Nitroprusside.
Dantrolene The risk or severity of hyperkalemia can be increased when Dantrolene is combined with Seletracetam.
Lithium citrate The risk or severity of adverse effects can be increased when Seletracetam is combined with Lithium citrate.
Lithium carbonate The risk or severity of adverse effects can be increased when Seletracetam is combined with Lithium carbonate.
Lithium hydroxide The risk or severity of adverse effects can be increased when Seletracetam is combined with Lithium hydroxide.
Boceprevir The serum concentration of Seletracetam can be increased when it is combined with Boceprevir.
Ibutilide Ibutilide may increase the arrhythmogenic activities of Seletracetam.
Hyoscyamine Hyoscyamine may increase the arrhythmogenic activities of Seletracetam.
Atropine Atropine may increase the arrhythmogenic activities of Seletracetam.
Adenosine Adenosine may increase the arrhythmogenic activities of Seletracetam.
Moricizine Moricizine may increase the arrhythmogenic activities of Seletracetam.
Levosimendan Levosimendan may increase the arrhythmogenic activities of Seletracetam.
Procainamide Procainamide may increase the arrhythmogenic activities of Seletracetam.
Tocainide Tocainide may increase the arrhythmogenic activities of Seletracetam.
Flecainide Flecainide may increase the arrhythmogenic activities of Seletracetam.
Encainide Encainide may increase the arrhythmogenic activities of Seletracetam.
Ajmaline Ajmaline may increase the arrhythmogenic activities of Seletracetam.
Aprindine Aprindine may increase the arrhythmogenic activities of Seletracetam.
Azimilide Azimilide may increase the arrhythmogenic activities of Seletracetam.
Carteolol Seletracetam may increase the arrhythmogenic activities of Carteolol.
Metipranolol Seletracetam may increase the arrhythmogenic activities of Metipranolol.
Tedisamil Seletracetam may increase the arrhythmogenic activities of Tedisamil.
Vernakalant Seletracetam may increase the arrhythmogenic activities of Vernakalant.
Cariporide Seletracetam may increase the arrhythmogenic activities of Cariporide.
Xylometazoline Seletracetam may increase the arrhythmogenic activities of Xylometazoline.
Sparteine Seletracetam may increase the arrhythmogenic activities of Sparteine.
Fasudil Seletracetam may increase the arrhythmogenic activities of Fasudil.
Melperone Seletracetam may increase the arrhythmogenic activities of Melperone.
Tropisetron Seletracetam may increase the arrhythmogenic activities of Tropisetron.
Simendan Seletracetam may increase the arrhythmogenic activities of Simendan.
Spiradoline Seletracetam may increase the arrhythmogenic activities of Spiradoline.
Pilsicainide Seletracetam may increase the arrhythmogenic activities of Pilsicainide.
Cicletanine Seletracetam may increase the arrhythmogenic activities of Cicletanine.
Cibenzoline Seletracetam may increase the arrhythmogenic activities of Cibenzoline.
Nizofenone Seletracetam may increase the arrhythmogenic activities of Nizofenone.
Prajmaline Seletracetam may increase the arrhythmogenic activities of Prajmaline.
Tiracizine Seletracetam may increase the arrhythmogenic activities of Tiracizine.
Ethacizine Seletracetam may increase the arrhythmogenic activities of Ethacizine.
Lorajmine Seletracetam may increase the arrhythmogenic activities of Lorajmine.
Bunaftine Seletracetam may increase the arrhythmogenic activities of Bunaftine.
Lorcainide Seletracetam may increase the arrhythmogenic activities of Lorcainide.
Hydroquinine Seletracetam may increase the arrhythmogenic activities of Hydroquinine.
Bioallethrin Seletracetam may increase the arrhythmogenic activities of Bioallethrin.
Fosfructose Seletracetam may increase the arrhythmogenic activities of Fosfructose.
Hydroquinidine Seletracetam may increase the arrhythmogenic activities of Hydroquinidine.
SOR-C13 Seletracetam may increase the arrhythmogenic activities of SOR-C13.
Digoxin Digoxin may increase the arrhythmogenic activities of Seletracetam.
Acetyldigitoxin Acetyldigitoxin may increase the arrhythmogenic activities of Seletracetam.
Deslanoside Deslanoside may increase the arrhythmogenic activities of Seletracetam.
Cymarin Seletracetam may increase the arrhythmogenic activities of Cymarin.
Metildigoxin Seletracetam may increase the arrhythmogenic activities of Metildigoxin.
Acetyldigoxin Seletracetam may increase the arrhythmogenic activities of Acetyldigoxin.
Niguldipine Seletracetam may increase the arrhythmogenic activities of Niguldipine.
Bretylium Bretylium may increase the arrhythmogenic activities of Seletracetam.
Isradipine Isradipine may increase the arrhythmogenic activities of Seletracetam.
Diltiazem Diltiazem may increase the arrhythmogenic activities of Seletracetam.
Trimethadione Trimethadione may increase the arrhythmogenic activities of Seletracetam.
Amlodipine Amlodipine may increase the arrhythmogenic activities of Seletracetam.
Nimodipine Nimodipine may increase the arrhythmogenic activities of Seletracetam.
Lercanidipine Lercanidipine may increase the arrhythmogenic activities of Seletracetam.
Lamotrigine Lamotrigine may increase the arrhythmogenic activities of Seletracetam.
Cinnarizine Cinnarizine may increase the arrhythmogenic activities of Seletracetam.
Nicardipine Nicardipine may increase the arrhythmogenic activities of Seletracetam.
Verapamil Verapamil may increase the arrhythmogenic activities of Seletracetam.
Losartan Losartan may increase the arrhythmogenic activities of Seletracetam.
Levomenthol Levomenthol may increase the arrhythmogenic activities of Seletracetam.
Zonisamide Zonisamide may increase the arrhythmogenic activities of Seletracetam.
Nitrendipine Nitrendipine may increase the arrhythmogenic activities of Seletracetam.
Perhexiline Perhexiline may increase the arrhythmogenic activities of Seletracetam.
Bepridil Bepridil may increase the arrhythmogenic activities of Seletracetam.
Nimesulide Nimesulide may increase the arrhythmogenic activities of Seletracetam.
Prenylamine Prenylamine may increase the arrhythmogenic activities of Seletracetam.
Cyclandelate Cyclandelate may increase the arrhythmogenic activities of Seletracetam.
Flunarizine Flunarizine may increase the arrhythmogenic activities of Seletracetam.
Fluspirilene Fluspirilene may increase the arrhythmogenic activities of Seletracetam.
Clevidipine Clevidipine may increase the arrhythmogenic activities of Seletracetam.
Methsuximide Methsuximide may increase the arrhythmogenic activities of Seletracetam.
Nylidrin Seletracetam may increase the arrhythmogenic activities of Nylidrin.
Ziconotide Seletracetam may increase the arrhythmogenic activities of Ziconotide.
Dotarizine Seletracetam may increase the arrhythmogenic activities of Dotarizine.
Nilvadipine Seletracetam may increase the arrhythmogenic activities of Nilvadipine.
Tranilast Seletracetam may increase the arrhythmogenic activities of Tranilast.
Agmatine Seletracetam may increase the arrhythmogenic activities of Agmatine.
Fendiline Seletracetam may increase the arrhythmogenic activities of Fendiline.
Eperisone Seletracetam may increase the arrhythmogenic activities of Eperisone.
Trimebutine Seletracetam may increase the arrhythmogenic activities of Trimebutine.
Pinaverium Seletracetam may increase the arrhythmogenic activities of Pinaverium.
Nicorandil Seletracetam may increase the arrhythmogenic activities of Nicorandil.
Barnidipine Seletracetam may increase the arrhythmogenic activities of Barnidipine.
Aranidipine Seletracetam may increase the arrhythmogenic activities of Aranidipine.
Azelnidipine Seletracetam may increase the arrhythmogenic activities of Azelnidipine.
Benidipine Seletracetam may increase the arrhythmogenic activities of Benidipine.

Target Protein

Synaptic vesicle glycoprotein 2A SV2A
Voltage-dependent N-type calcium channel subunit alpha-1B CACNA1B
Glycine receptor (alpha-1/beta) GLRA1

Referensi & Sumber

Synthesis reference: 1. Wong MG, Defina JA, Andrews PR: Conformational analysis of clinically active anticonvulsant drugs. Journal of Medical Chemistry 1986 (29): 562-72. PubMed: 3959032 2. Bruno-Blanch L, Gálvez J, García-Domenech R: Topological virtual screening: a way to find new anticonvulsant drugs from chemical diversity 2003 (13): 2749-54. PubMed: 12873507 3. Kami?ski K, Rzepka S ,Obniska J: Synthesis and anticonvulsant activity of new 1-2-oxo-2-(4-phenylpiperazin-1-yl)ethylpyrrolidine-2,5-diones. Bioorganic & Medicinal Chemistry Letters 2011; 21 (19): 5800–3. PubMed: 21875804
Artikel (PubMed)
  • PMID: 17199025
    Bennett B, Matagne A, Michel P, Leonard M, Cornet M, Meeus MA, Toublanc N: Seletracetam (UCB 44212). Neurotherapeutics. 2007 Jan;4(1):117-22.
  • PMID: 16732716
    Bialer M: New antiepileptic drugs that are second generation to existing antiepileptic drugs. Expert Opin Investig Drugs. 2006 Jun;15(6):637-47.
  • PMID: 16556440
    Gillard M, Chatelain P, Fuks B: Binding characteristics of levetiracetam to synaptic vesicle protein 2A (SV2A) in human brain and in CHO cells expressing the human recombinant protein. Eur J Pharmacol. 2006 Apr 24;536(1-2):102-8. Epub 2006 Mar 10.
  • PMID: 23214383
    Ziolkowski H, Jaroszewski JJ, Ziolkowska N, Jasiecka A: Characteristics of selected second-generation antiepileptic drugs used in dogs. Pol J Vet Sci. 2012;15(3):571-82.
  • PMID: 20167814
    de Groot M, Toering ST, Boer K, Spliet WG, Heimans JJ, Aronica E, Reijneveld JC: Expression of synaptic vesicle protein 2A in epilepsy-associated brain tumors and in the peritumoral cortex. Neuro Oncol. 2010 Mar;12(3):265-73. doi: 10.1093/neuonc/nop028. Epub 2010 Jan 6.
  • PMID: 19443931
    Luszczki JJ: Third-generation antiepileptic drugs: mechanisms of action, pharmacokinetics and interactions. Pharmacol Rep. 2009 Mar-Apr;61(2):197-216.
  • PMID: 17158031
    Bialer M, Johannessen SI, Kupferberg HJ, Levy RH, Perucca E, Tomson T: Progress report on new antiepileptic drugs: a summary of the Eigth Eilat Conference (EILAT VIII). Epilepsy Res. 2007 Jan;73(1):1-52. Epub 2006 Dec 8.
Textbook
  • ISBN: 0-632-06046-8
    59. (2004). In The Treatment of Epilepsy (2nd ed., pp. 736). John Wiley & Sons.

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