Drug Information

Drug (ID: DG00640) and It's Reported Resistant Information

• Name: Levetiracetam
• Synonyms: Levetiracetam; 102767-28-2; Keppra; (S)-2-(2-Oxopyrrolidin-1-yl)butanamide; Keppra XR; (2S)-2-(2-oxopyrrolidin-1-yl)butanamide; ucb L059; UCB-L 059; Levetiracetamum; Spritam; UCB-L059; (S)-alpha-Ethyl-2-oxo-1-pyrrolidineacetamide; SIB-S1; Levetiracetame; (-)-(S)-alpha-Ethyl-2-oxo-1-pyrrolidineacetamide; UNII-44YRR34555; MFCD03265610; UCB-22059; Levetiracetamum [INN-Latin]; 1-Pyrrolidineacetamide, alpha-ethyl-2-oxo-, (alphaS)-; CHEBI:6437; Levetiracetam In Sodium Chloride; UCB 22059; 44YRR34555; NSC-760119; Levroxa; (S)-(-)-alpha-ethyl-2-oxo-1-pyrrolidineacetamide; matever; Leviteracetam; Levipil; Torleva; Elepsia XR; (S)-Levetiracetam; SMR000466303; Keppra (TN); Levesam 500; Etiracetam levo-isomer; SR-01000759400; Elepsia; Levetiracetam sun; E Keppra; HSDB 7528; Levetiracetam teva; N03AX14; Levetiracetam accord; Levetiracetam [USAN:USP:INN:BAN]; Levetiracetam actavis; Levetiracetam hospira; E keppra (TN); Levetiracetam solution; Levetiracetam- Bio-X; (S)-2-(2-Oxo-1-pyrrolidinyl)butyramide; L-059; 2(S)-(2-OXOPYRROLIDIN-1-YL)BUTYRAMIDE; CHEMBL1286; 1-Pyrrolidineacetamide, alpha-ethyl-2-oxo-, (S)-; MLS000759403; MLS001424069; MLS006010215; BIDD:GT0242; SCHEMBL118843; GTPL6826; Levetiracetam (JAN/USP/INN); DTXSID9023207; AGB-101; Levetiracetam, >=98% (HPLC); Levetiracetam, analytical standard; HMS2051D07; HMS2089L20; HMS2235I18; HMS3262H11; HMS3713P16; HMS3884O11; Pharmakon1600-01502265; ACT02712; ALBB-027275; BCP11856; HY-B0106; ZINC1547851; Tox21_500835; BDBM50422542; NSC760119; s1356; STL388027; Levetiracetam 1.0 mg/ml in Methanol; AKOS015841981; AC-1479; CCG-100928; CS-1854; DB01202; KS-1176; LP00835; LS41261; MCULE-5120797917; NC00178; NSC 760119; SDCCGSBI-0633760.P001; (2S)-(2-Oxopyrrolidin-1-yl)butyramide; NCGC00186028-01; NCGC00186028-13; NCGC00261520-01; (S)-2-(2-oxopyrrolidin-1-yl)butyramide; BL164623; (s)-2-(2-oxopyrrolidin-1-yl) butyramide; AM20070676; L0234; SW197558-3; C07841; D00709; AB00639945-06; AB00639945_07; AB00639945_08; 767L282; A800616; (S)-2-(2-OXO-PYRROLIDIN-1-YL)-BUTYRAMIDE; Q-201292; SR-01000759400-4; SR-01000759400-5; (2S)-2-(2-oxopyrrolidin-1-yl)butanamide;Levetiracetam; (ALPHAS)-ALPHA-ETHYL-2-OXO-1-PYRROLIDINEACETAMIDE; UNII-230447L0GL component HPHUVLMMVZITSG-LURJTMIESA-N; Levetiracetam, European Pharmacopoeia (EP) Reference Standard; Levetiracetam, United States Pharmacopeia (USP) Reference Standard; (-)-(S)-alpha-ethyl-2-oxo-1-pyrrolidineacetamide (2S)-2-(2-Oxo-pyrrolidin-1-yl)butanamide; Levetiracetam solution, 1.0 mg/mL in methanol, ampule of 1 mL, certified reference material; Levitiracetam, Pharmaceutical Secondary Standard; Certified Reference Material
• Indication:
  In total 2 Indication(s)
  Epilepsy [ICD-11: 8A60]; Approved; [1]
  Fibromyalgia [ICD-11: MG30]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Validated by in-vivo Model for This Drug (1 diseases)
  Epilepsy [ICD-11: 8A60]; [2]
  Disease(s) with Clinically Reported Resistance for This Drug (2 diseases)
  Genetic epileptic syndromes [ICD-11: 8A61]; [3]
  Seizures [ICD-11: 8A68]; [4]
• Target: 5-HT 3A receptor (HTR3A); 5HT3A_HUMAN; [1]
• Target: Synaptic vesicle glycoprotein 2A (SV2A); SV2A_HUMAN; [1]
• Formula: C8H14N2O2
• IsoSMILES: CC[C@@H](C(=O)N)N1CCCC1=O
• InChI: 1S/C8H14N2O2/c1-2-6(8(9)12)10-5-3-4-7(10)11/h6H,2-5H2,1H3,(H2,9,12)/t6-/m0/s1
• InChIKey: HPHUVLMMVZITSG-LURJTMIESA-N
• PubChem CID: 5284583
• ChEBI ID: CHEBI:6437
• TTD Drug ID: D0E1XL
• VARIDT ID: DR00180
• DrugBank ID: DB01202

Type(s) of Resistant Mechanism of This Drug

  ADTT: Aberration of the Drug's Therapeutic Target

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-08: Nervous system diseases

Epilepsy [ICD-11: 8A60]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Key Molecule: Glutathione synthetase (GSH) [2]

• Resistant Disease: mitochondrial refractory epilepsy [ICD-11: 8A60.A]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• In Vivo Model: Swiss albino mice model; Mus musculus
• Experiment for Molecule Alteration: Ellman assay
• Experiment for Drug Resistance: Pre-treatment resistance testing; Post-treatment resistance testing
• Mechanism Description: The involvement of complex I in drug resistance is well established in epilepsy; therefore, the model chosen for this study was rotenone corneal kindled model of drug resistance using rotenone as a selective irreversible inhibitor of complex I, which have shown resistance to drugs such as valproate, levetiracetam, lamotrigine, pregabalin, carbamazepine, zonisamide, topiramate, gabapentin and their combinations

Key Molecule: Quinone reductase 1 (NQO1) [2]

• Resistant Disease: mitochondrial refractory epilepsy [ICD-11: 8A60.A]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Discovered Using In-vivo Testing Model
• Cell Pathway Regulation: Nrf2 signaling pathway; Inhibition; hsa05208
• In Vivo Model: Swiss albino mice model; Mus musculus
• Experiment for Molecule Alteration: ELISA assay
• Experiment for Drug Resistance: Pre-treatment resistance testing; Post-treatment resistance testing
• Mechanism Description: The involvement of complex I in drug resistance is well established in epilepsy; therefore, the model chosen for this study was rotenone corneal kindled model of drug resistance using rotenone as a selective irreversible inhibitor of complex I, which have shown resistance to drugs such as valproate, levetiracetam, lamotrigine, pregabalin, carbamazepine, zonisamide, topiramate, gabapentin and their combinations

Genetic epileptic syndromes [ICD-11: 8A61]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Potassium inwardly rectifying channel subfamily J member 10 (KCNJ10) [1]

• Sensitive Disease: Genetic generalized epilepsies [ICD-11: 8A61.0]
• Molecule Alteration: SNP; rs12402969 C+ Genotypes CC+CT
• Experimental Note: Identified from the Human Clinical Data
• Experiment for Molecule Alteration: Genotyping assay
• Mechanism Description: By analyzing the association between KCNJ10 polymorphisms and anti-epileptic drug efficacy of GGEs we found the frequency of rs12402969 C allele and CC+CT genotypes were higher in GGEs drug responsive patients than that in drug resistant patients

References

• Ref 1: Common variants of KCNJ10 are associated with susceptibility and anti-epileptic drug resistance in Chinese genetic generalized epilepsies .PLoS One. 2015 Apr 13;10(4):e0124896. doi: 10.1371/journal.pone.0124896. eCollection 2015. 10.1371/journal.pone.0124896
• Ref 2: Attenuation of mitochondrial refractory epilepsy in rotenone corneal kindling model of drug resistance by idebenone: An approach to bypass mitochondrial complex I. Epilepsy Res. 2024 Nov;207:107458.
• Ref 3: Drug-Resistant Juvenile Myoclonic Epilepsy: Misdiagnosis of Progressive Myoclonus EpilepsyFront Neurol. 2019 Sep 10;10:946. doi: 10.3389/fneur.2019.00946. eCollection 2019.
• Ref 4: Phenotypes in Children With SYNGAP1 Encephalopathy in ChinaFront Neurosci. 2021 Dec 2;15:761473. doi: 10.3389/fnins.2021.761473. eCollection 2021.