Details of the Drug Combination

General Information of Drug Combination (ID: DCFERNX)

• Drug Combination Name: Lamotrigine + Levetiracetam
• Indication: Epilepsy; Status: Phase 1 [1]
• Component Drugs:
  Lamotrigine (DM8SXYG): Small molecular drug
  Levetiracetam (DMTGDN8): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Lamotrigine

Disease Entry	ICD 11	Status	REF
Bipolar disorder	6A60	Approved	[2]
Epilepsy	8A60-8A68	Approved	[2]

Lamotrigine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Voltage-gated sodium channel alpha Nav1.9 (SCN11A)	TTN9VTF	SCNBA_HUMAN	Blocker	[6]

Lamotrigine Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[7]
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[8]

Lamotrigine Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[9]
UDP-glucuronosyltransferase 1A3 (UGT1A3)	DEF2WXN	UD13_HUMAN	Metabolism	[10]
UDP-glucuronosyltransferase 1A4 (UGT1A4)	DELOY3P	UD14_HUMAN	Metabolism	[11]

Lamotrigine Interacts with 8 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Decreases Activity	[12]
3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 2 (HSD3B2)	OT02MSKN	3BHS2_HUMAN	Decreases Activity	[13]
Steroidogenic acute regulatory protein, mitochondrial (STAR)	OTFEZ5AI	STAR_HUMAN	Decreases Expression	[14]
POU domain, class 5, transcription factor 1 (POU5F1)	OTDHHN7O	PO5F1_HUMAN	Decreases Expression	[14]
Sodium channel protein type 2 subunit alpha (SCN2A)	OTUSYE4Z	SCN2A_HUMAN	Decreases Activity	[15]
Protein lin-28 homolog A (LIN28A)	OTJJBRCQ	LN28A_HUMAN	Decreases Expression	[14]
Adrenocorticotropic hormone receptor (MC2R)	OT6V19Y9	ACTHR_HUMAN	Increases Response To Substance	[16]
D(2) dopamine receptor (DRD2)	OTBLXKEG	DRD2_HUMAN	Increases Response To Substance	[16]

Indication(s) of Levetiracetam

Disease Entry	ICD 11	Status	REF
Epilepsy	8A60-8A68	Approved	[3]
Fibromyalgia	MG30.01	Approved	[4]

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	[4]
Synaptic vesicle glycoprotein 2A (SV2A)	TTT3P91	SV2A_HUMAN	Modulator	[17]

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	[18]

Levetiracetam Interacts with 3 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Decreases Activity	[12]
3 beta-hydroxysteroid dehydrogenase/Delta 5-->4-isomerase type 2 (HSD3B2)	OT02MSKN	3BHS2_HUMAN	Decreases Expression	[19]
Steroidogenic acute regulatory protein, mitochondrial (STAR)	OTFEZ5AI	STAR_HUMAN	Decreases Expression	[19]

References

• [1] ClinicalTrials.gov (NCT05450822) Precision Medicine in the Treatment of Epilepsy
• [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: 2622).
• [3] 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).
• [4] Emerging therapies for fibromyalgia. Expert Opin Emerg Drugs. 2008 Mar;13(1):53-62.
• [5] Expression of the human UGT1 locus in transgenic mice by 4-chloro-6-(2,3-xylidino)-2-pyrimidinylthioacetic acid (WY-14643) and implications on drug metabolism through peroxisome proliferator-activated receptor alpha activation. Drug Metab Dispos. 2007 Mar;35(3):419-27.
• [6] The effects of lamotrigine on the acquisition and expression of morphine-induced place preference in mice. Pak J Biol Sci. 2009 Jan 1;12(1):33-9.
• [7] Several major antiepileptic drugs are substrates for human P-glycoprotein. Neuropharmacology. 2008 Dec;55(8):1364-75.
• [8] Lamotrigine is a substrate for OCT1 in brain endothelial cells. Biochem Pharmacol. 2012 Mar 15;83(6):805-14.
• [9] Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos. 2004 Nov;32(11):1201-8.
• [10] Variation in glucuronidation of lamotrigine in human liver microsomes. Xenobiotica. 2009 May;39(5):355-63.
• [11] Studies on induction of lamotrigine metabolism in transgenic UGT1 mice. Xenobiotica. 2009 Nov;39(11):826-35.
• [12] 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.
• [13] Effects of anticonvulsants on human p450c17 (17alpha-hydroxylase/17,20 lyase) and 3beta-hydroxysteroid dehydrogenase type 2. Epilepsia. 2005 Mar;46(3):444-8.
• [14] Antiepileptic drugs are endocrine disruptors for the human fetal testis ex vivo. Toxicol Sci. 2023 Sep 28;195(2):169-183. doi: 10.1093/toxsci/kfad076.
• [15] Electrophysiological and pharmacological properties of the human brain type IIA Na+ channel expressed in a stable mammalian cell line. Pflugers Arch. 2001 Jan;441(4):425-33. doi: 10.1007/s004240000448.
• [16] Genetic association study of treatment response with olanzapine/fluoxetine combination or lamotrigine in bipolar I depression. J Clin Psychiatry. 2010 May;71(5):599-605. doi: 10.4088/JCP.08m04632gre. Epub 2009 Dec 15.
• [17] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [18] 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.
• [19] Differential effects of antiepileptic drugs on steroidogenesis in a human in vitro cell model. Acta Neurol Scand Suppl. 2009;(189):14-21.