Details of the Drug Combination

General Information of Drug Combination (ID: DCK4JJ7)

• Drug Combination Name: Lorazepam + Clonazepam
• Indication: Epilepsia Partialis Continua; Status: Phase 3 [1]
• Component Drugs:
  Lorazepam (DM84ZXF): Small molecular drug
  Clonazepam (DMTO13J): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Lorazepam

Disease Entry	ICD 11	Status	REF
Absence epilepsy	N.A.	Approved	[2]
Anxiety	N.A.	Approved	[2]
Anxiety disorder	6B00-6B0Z	Approved	[3]
Nausea	MD90	Approved	[2]
Panic disorder	6B01	Approved	[2]
Vomiting	MD90	Approved	[2]

Lorazepam Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Translocator protein (TSPO)	TTPTXIN	TSPO_HUMAN	Modulator	[6]

Lorazepam Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
UDP-glucuronosyltransferase 2B7 (UGT2B7)	DEB3CV1	UD2B7_HUMAN	Metabolism	[7]
UDP-glucuronosyltransferase 2B15 (UGT2B15)	DENZ6B1	UDB15_HUMAN	Metabolism	[8]

Indication(s) of Clonazepam

Disease Entry	ICD 11	Status	REF
Absence epilepsy	N.A.	Approved	[4]
Epilepsy	8A60-8A68	Approved	[5]
Panic disorder	6B01	Approved	[4]
Seizure disorder	8A6Z	Phase 2	[5]

Clonazepam Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Gamma-aminobutyric acid receptor (GAR)	TTNJYV2	NOUNIPROTAC	Agonist	[9]

Clonazepam Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[10]
RNA cytidine acetyltransferase (hALP)	DEZV4AP	NAT10_HUMAN	Metabolism	[11]
Oxygen-insensitive NADPH nitroreductase B (nfsB)	DE0QLUZ	NFSB_ECOLI	Metabolism	[12]

References

• [1] ClinicalTrials.gov (NCT02134366) Clobazam Use in Epilepsia Partialis Continua - Pilot Study
• [2] Lorazepam FDA Label
• [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: 5884).
• [4] Clonazepam FDA Label
• [5] 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: 6963).
• [6] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [7] Pharmacokinetic and pharmacodynamic interaction of lorazepam and valproic acid in relation to UGT2B7 genetic polymorphism in healthy subjects. Clin Pharmacol Ther. 2008 Apr;83(4):595-600.
• [8] Effect of the UGT2B15 genotype on the pharmacokinetics, pharmacodynamics, and drug interactions of intravenous lorazepam in healthy volunteers. Clin Pharmacol Ther. 2005 Jun;77(6):486-94.
• [9] Glutamate- and GABA-based CNS therapeutics. Curr Opin Pharmacol. 2006 Feb;6(1):7-17.
• [10] Identification of the human and animal hepatic cytochromes P450 involved in clonazepam metabolism. Fundam Clin Pharmacol. 1993;7(2):69-75.
• [11] Effect of common NAT2 variant alleles in the acetylation of the major clonazepam metabolite, 7-aminoclonazepam. Drug Metab Lett. 2007 Jan;1(1):3-5.
• [12] Characterization of Escherichia coli nitroreductase NfsB in the metabolism of nitrobenzodiazepines. Biochem Pharmacol. 2009 Jul 1;78(1):96-103.