Details of the Drug Combination

General Information of Drug Combination (ID: DCFFSPE)

Drug Combination Name
Methyldopa Labetalol
Indication
Disease Entry Status REF
Hypertension, Pregnancy-Induced Phase 4 [1]
Component Drugs Methyldopa   DM5I621 Labetalol   DMK8U72
Small molecular drug Small molecular drug
2D MOL 2D MOL
3D MOL 3D MOL

Molecular Interaction Atlas of This Drug Combination

Molecular Interaction Atlas (MIA)
Indication(s) of Methyldopa
Disease Entry ICD 11 Status REF
Hypertension BA00-BA04 Approved [2]
Methyldopa Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Dopamine D2 receptor (D2R) TTEX248 DRD2_HUMAN Agonist [5]
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Methyldopa Interacts with 4 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Metabolism [6]
Sulfotransferase 1A1 (SULT1A1) DEYWLRK ST1A1_HUMAN Metabolism [7]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [6]
Thiopurine methyltransferase (TPMT) DEFQ8VO TPMT_HUMAN Metabolism [8]
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Indication(s) of Labetalol
Disease Entry ICD 11 Status REF
Hypertension BA00-BA04 Approved [3]
Hypertension, pregnancy-induced N.A. Approved [4]
Malignant essential hypertension BA00 Approved [4]
Labetalol Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
Adrenergic receptor Alpha-1 (ADRA1) TTG28O6 NOUNIPROTAC Antagonist [9]
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Labetalol Interacts with 2 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [10]
Organic anion transporting polypeptide 1A2 (SLCO1A2) DTE2B1D SO1A2_HUMAN Substrate [11]
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Labetalol Interacts with 6 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Metabolism [12]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [13]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Metabolism [14]
UDP-glucuronosyltransferase 2B7 (UGT2B7) DEB3CV1 UD2B7_HUMAN Metabolism [12]
UDP-glucuronosyltransferase 1A9 (UGT1A9) DE85D2P UD19_HUMAN Metabolism [12]
UDP-glucuronosyltransferase 2B4 (UGT2B4) DENUPDX UD2B4_HUMAN Metabolism [12]
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⏷ Show the Full List of 6 DME(s)
Labetalol Interacts with 5 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Renin (REN) OT52GZR2 RENI_HUMAN Decreases Activity [15]
Natriuretic peptides A (NPPA) OTMQNTNX ANF_HUMAN Decreases Activity [15]
Beta-2 adrenergic receptor (ADRB2) OTSDOX4Q ADRB2_HUMAN Decreases Activity [16]
Beta-1 adrenergic receptor (ADRB1) OTQBWN4U ADRB1_HUMAN Decreases Activity [16]
Phosphatidylcholine translocator ABCB4 (ABCB4) OTE6PY83 MDR3_HUMAN Decreases Activity [17]
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References

1 ClinicalTrials.gov (NCT02531490) Early Vascular Adjustments During Hypertensive Pregnancy
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: 5217).
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: 7207).
4 Labetalol FDA Label
5 Centrally acting antihypertensive agents: an update. J Clin Hypertens (Greenwich). 2007 May;9(5):399-405.
6 Lack of interaction between amiodarone and mexiletine in cardiac arrhythmia patients. J Clin Pharmacol. 2002 Mar;42(3):342-6.
7 Platelet phenol sulfotransferase and erythrocyte catechol-O-methyltransferase activities: correlation with methyldopa metabolism. Clin Pharmacol Ther. 1984 Jan;35(1):55-63.
8 Identification, characterization, and ontogenic study of a catechol O-methyltransferase from zebrafish. Aquat Toxicol. 2011 Mar;102(1-2):18-23.
9 Beta-blockers in the treatment of hypertension: are there clinically relevant differences Postgrad Med. 2009 May;121(3):90-8.
10 Human intestinal transporter database: QSAR modeling and virtual profiling of drug uptake, efflux and interactions. Pharm Res. 2013 Apr;30(4):996-1007.
11 Involvement of influx and efflux transport systems in gastrointestinal absorption of celiprolol. J Pharm Sci. 2009 Jul;98(7):2529-39.
12 Regulation of UDP-glucuronosyltransferase (UGT) 1A1 by progesterone and its impact on labetalol elimination. Xenobiotica. 2008 Jan;38(1):62-75.
13 Comparison of verapamil, diltiazem, and labetalol on the bioavailability and metabolism of imipramine. J Clin Pharmacol. 1992 Feb;32(2):176-83.
14 Drug Interactions Flockhart Table
15 Hemodynamic and humoral effects of intravenous dilevalol in patients with moderate hypertension. Am J Cardiol. 1989 Jun 5;63(19):34I-37I. doi: 10.1016/0002-9149(89)90126-4.
16 Preclinical pharmacologic properties of dilevalol, an antihypertensive agent possessing selective beta 2 agonist-mediated vasodilation and beta antagonism. Am J Cardiol. 1989 Jun 5;63(19):3I-6I. doi: 10.1016/0002-9149(89)90120-3.
17 Evaluating the Role of Multidrug Resistance Protein 3 (MDR3) Inhibition in Predicting Drug-Induced Liver Injury Using 125 Pharmaceuticals. Chem Res Toxicol. 2017 May 15;30(5):1219-1229. doi: 10.1021/acs.chemrestox.7b00048. Epub 2017 May 4.