Details of the Drug Combination

General Information of Drug Combination (ID: DC8IOQB)

• Drug Combination Name: Levetiracetam + Lacosamide
• Indication: Epilepsy; Status: Phase 1 [1]
• Component Drugs:
  Levetiracetam (DMTGDN8): Small molecular drug
  Lacosamide (DMVM6QR): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Levetiracetam

Disease Entry	ICD 11	Status	REF
Epilepsy	8A60-8A68	Approved	[2]
Fibromyalgia	MG30.01	Approved	[3]

Levetiracetam Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
5-HT 3A receptor (HTR3A)	TTPC4TU	5HT3A_HUMAN	Antagonist	[3]
Synaptic vesicle glycoprotein 2A (SV2A)	TTT3P91	SV2A_HUMAN	Modulator	[6]

Levetiracetam Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[7]

Levetiracetam Interacts with 6 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Decreases Activity	[8]
Steroid 17-alpha-hydroxylase/17,20 lyase (CYP17A1)	OTZKVLVJ	CP17A_HUMAN	Decreases Expression	[9]
Aromatase (CYP19A1)	OTZ6XF74	CP19A_HUMAN	Decreases Expression	[9]
3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 2 (HSD3B2)	OT02MSKN	3BHS2_HUMAN	Decreases Expression	[9]
Steroidogenic acute regulatory protein, mitochondrial (STAR)	OTFEZ5AI	STAR_HUMAN	Decreases Expression	[9]
Serum paraoxonase/arylesterase 1 (PON1)	OTD0Z2XO	PON1_HUMAN	Affects Activity	[10]

Indication(s) of Lacosamide

Disease Entry	ICD 11	Status	REF
Convulsion	8A68.Z	Approved	[4]
Epilepsy	8A60-8A68	Approved	[5]
Diabetic neuropathy	8C0Z	Phase 3	[4]

Lacosamide Interacts with 3 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Voltage-gated sodium channel alpha Nav1.9 (SCN11A)	TTN9VTF	SCNBA_HUMAN	Inhibitor	[5]
Voltage-gated sodium channel (Nav)	TTIG65Q	NOUNIPROTAC	Inhibitor	[5]
Dihydropyrimidinase related protein 2 (DPYSL2)	TTZCW3T	DPYL2_HUMAN	Modulator	[11]

Lacosamide Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[12]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[13]

References

• [1] ClinicalTrials.gov (NCT01345058) Add on Lacosamide Versus High Dose Monotherapy
• [2] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 6826).
• [3] Emerging therapies for fibromyalgia. Expert Opin Emerg Drugs. 2008 Mar;13(1):53-62.
• [4] URL: http://www.guidetopharmacology.org Nucleic Acids Res. 2015 Oct 12. pii: gkv1037. The IUPHAR/BPS Guide to PHARMACOLOGY in 2016: towards curated quantitative interactions between 1300 protein targets and 6000 ligands. (Ligand id: 7472).
• [5] Antibodies and venom peptides: new modalities for ion channels. Nat Rev Drug Discov. 2019 May;18(5):339-357.
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [7] Differences in the transport of the antiepileptic drugs phenytoin, levetiracetam and carbamazepine by human and mouse P-glycoprotein. Neuropharmacology. 2007 Feb;52(2):333-46.
• [8] Functional evaluation of polymorphisms in the human ABCB1 gene and the impact on clinical responses of antiepileptic drugs. Pharmacogenet Genomics. 2008 May;18(5):390-402. doi: 10.1097/FPC.0b013e3282f85e36.
• [9] Differential effects of antiepileptic drugs on steroidogenesis in a human in vitro cell model. Acta Neurol Scand Suppl. 2009;(189):14-21.
• [10] Antiepileptic drugs: impacts on human serum paraoxonase-1. J Biochem Mol Toxicol. 2017 Jun;31(6).
• [11] 2008 FDA drug approvals. Nat Rev Drug Discov. 2009 Feb;8(2):93-6.
• [12] Lacosamide: what can be expected from the next new antiepileptic drug? Epilepsy Curr. 2009 Sep-Oct;9(5):133-4.
• [13] Lacosamide therapeutic monitoring in patients with epilepsy: effect of concomitant antiepileptic drugs. Ther Drug Monit. 2013 Dec;35(6):849-52.