Details of the Drug Combination

General Information of Drug Combination (ID: DCRH4DS)

• Drug Combination Name: Varenicline + Prazosin
• Indication: Cigarette Smoking; Status: Phase 1 [1]
• Component Drugs:
  Varenicline (DMMUOLJ): Small molecular drug
  Prazosin (DMCD9YG): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Varenicline

Disease Entry	ICD 11	Status	REF
Drug dependence	N.A.	Approved	[2]
Smoking dependence	6C4A.2	Approved	[3]

Varenicline Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Neuronal acetylcholine receptor alpha-4/beta-2 (CHRNA4/B2)	TTL1ATN	ACHA4_HUMAN; ACHB2_HUMAN	Modulator	[6]

Varenicline Interacts with 2 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
Organic cation transporter 2 (SLC22A2)	DT9IDPW	S22A2_HUMAN	Substrate	[7]
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[8]

Indication(s) of Prazosin

Disease Entry	ICD 11	Status	REF
Benign prostatic hyperplasia	GA90	Approved	[4]
Congestive heart failure	BD10	Approved	[4]
Hypertension	BA00-BA04	Approved	[4]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2	[5]

Prazosin 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]

Prazosin Interacts with 3 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[10]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[11]
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[12]

Prazosin Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 1A1 (CYP1A1)	DE6OQ3W	CP1A1_HUMAN	Metabolism	[13]

References

• [1] ClinicalTrials.gov (NCT02193256) Varenicline + Prazosin for Heavy Drinking Smokers
• [2] Varenicline 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: 5459).
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [5] Prazosin to Prevent COVID-19 (PREVENT-COVID Trial) (PREVENT)
• [6] 2006 drug approvals: finding the niche. Nat Rev Drug Discov. 2007 Feb;6(2):99-101.
• [7] Effect of human renal cationic transporter inhibition on the pharmacokinetics of varenicline, a new therapy for smoking cessation: an in vitro-in vivo study. Clin Pharmacol Ther. 2008 Apr;83(4):567-76.
• [8] Identification of novel substrates and structure-activity relationship of cellular uptake mediated by human organic cation transporters 1 and 2. J Med Chem. 2013 Sep 26;56(18):7232-42.
• [9] Adventitia removal does not modify the alphaID-adrenoceptors response in aorta during hypertension and ageing. Auton Autacoid Pharmacol. 2009 Jul;29(3):117-33.
• [10] Evidence for two nonidentical drug-interaction sites in the human P-glycoprotein. Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10594-9.
• [11] P-glycoprotein and breast cancer resistance protein expression and function at the blood-brain barrier and blood-cerebrospinal fluid barrier (choroid plexus) in streptozotocin-induced diabetes in rats. Brain Res. 2011 Jan 25;1370:238-45.
• [12] Implications of genetic polymorphisms in drug transporters for pharmacotherapy. Cancer Lett. 2006 Mar 8;234(1):4-33.
• [13] Role of adrenoceptor-linked signaling pathways in the regulation of CYP1A1 gene expression. Biochem Pharmacol. 2005 Jan 15;69(2):277-87.