Details of the Drug Combination

General Information of Drug Combination (ID: DCLRE8B)

• Drug Combination Name: Prazosin + Naltrexone
• Indication: Alcohol Use Disorder; Status: Phase 2 [1]
• Component Drugs:
  Prazosin (DMCD9YG): Small molecular drug
  Naltrexone (DMUL45H): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Prazosin

Disease Entry	ICD 11	Status	REF
Benign prostatic hyperplasia	GA90	Approved	[2]
Congestive heart failure	BD10	Approved	[2]
Hypertension	BA00-BA04	Approved	[2]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2	[3]

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	[8]

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	[9]
Breast cancer resistance protein (ABCG2)	DTI7UX6	ABCG2_HUMAN	Substrate	[10]
Organic cation transporter 1 (SLC22A1)	DTT79CX	S22A1_HUMAN	Substrate	[11]

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	[12]

Indication(s) of Naltrexone

Disease Entry	ICD 11	Status	REF
Alcohol dependence	6C40.2	Approved	[2]
Chronic alcoholism	6C40.2Z	Approved	[4]
Crohn disease	DD70	Approved	[5]
Gastroparesis	DA41.00	Approved	[5]
Inflammatory bowel disease	DD72	Approved	[5]
Obesity	5B81	Approved	[5]
Ulcerative colitis	DD71	Approved	[5]
Human immunodeficiency virus infection	1C62	Phase 4	[6]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Phase 2	[7]
Chronic pain	MG30	Investigative	[5]

Naltrexone Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Opioid receptor (OPR)	TTN4QDT	NOUNIPROTAC	Antagonist	[13]

Naltrexone Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
UDP-glucuronosyltransferase 1A1 (UGT1A1)	DEYGVN4	UD11_HUMAN	Metabolism	[14]

Naltrexone Interacts with 9 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Nitric oxide synthase, inducible (NOS2)	OTKKIOJ1	NOS2_HUMAN	Decreases Activity	[15]
Follitropin subunit beta (FSHB)	OTGLS283	FSHB_HUMAN	Increases Expression	[16]
Lutropin subunit beta (LHB)	OT5GBOVJ	LSHB_HUMAN	Increases Expression	[16]
Mu-type opioid receptor (OPRM1)	OT16AAT8	OPRM_HUMAN	Affects Response To Substance	[13]
Mu-type opioid receptor (OPRM1)	OT16AAT8	OPRM_HUMAN	Increases Response	[13]
Sodium-dependent dopamine transporter (SLC6A3)	OT39XG28	SC6A3_HUMAN	Affects Response To Substance	[17]
Gamma-aminobutyric acid receptor subunit beta-2 (GABRB2)	OTAOZIGX	GBRB2_HUMAN	Affects Response To Substance	[18]
D(2) dopamine receptor (DRD2)	OTBLXKEG	DRD2_HUMAN	Affects Response To Substance	[18]
Gamma-aminobutyric acid receptor subunit alpha-6 (GABRA6)	OTX4UC3O	GBRA6_HUMAN	Affects Response To Substance	[18]

References

• [1] ClinicalTrials.gov (NCT02322047) Prazosin and Naltrexone (PaN) Study for Veterans With Alcohol Use Disorders
• [2] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [3] Prazosin to Prevent COVID-19 (PREVENT-COVID Trial) (PREVENT)
• [4] FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (ANDA) 074918.
• [5] Naltrexone FDA Label
• [6] 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: 1639).
• [7] ClinicalTrials.gov (NCT04365985) Study of Immunomodulation Using Naltrexone and Ketamine for COVID-19. U.S. National Institutes of Health.
• [8] Adventitia removal does not modify the alphaID-adrenoceptors response in aorta during hypertension and ageing. Auton Autacoid Pharmacol. 2009 Jul;29(3):117-33.
• [9] 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.
• [10] 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.
• [11] Implications of genetic polymorphisms in drug transporters for pharmacotherapy. Cancer Lett. 2006 Mar 8;234(1):4-33.
• [12] Role of adrenoceptor-linked signaling pathways in the regulation of CYP1A1 gene expression. Biochem Pharmacol. 2005 Jan 15;69(2):277-87.
• [13] An evaluation of mu-opioid receptor (OPRM1) as a predictor of naltrexone response in the treatment of alcohol dependence: results from the Combined Pharmacotherapies and Behavioral Interventions for Alcohol Dependence (COMBINE) study. Arch Gen Psychiatry. 2008 Feb;65(2):135-44.
• [14] In vivo chronic exposure to heroin or naltrexone selectively inhibits liver microsome formation of estradiol-3-glucuronide in the rat. Biochem Pharmacol. 2008 Sep 1;76(5):672-9.
• [15] Low dose naltrexone therapy in multiple sclerosis. Med Hypotheses. 2005;64(4):721-4.
• [16] Chronic naltrexone treatment induces desensitization of the luteinizing hormone pulse generator for opioid blockade in hyperprolactinemic patients. J Clin Endocrinol Metab. 1995 May;80(5):1739-42. doi: 10.1210/jcem.80.5.7745028.
• [17] Association between the Stin2 VNTR polymorphism of the serotonin transporter gene and treatment outcome in alcohol-dependent patients. Alcohol Alcohol. 2008 Sep-Oct;43(5):516-22. doi: 10.1093/alcalc/agn048. Epub 2008 Jun 14.
• [18] Predicting the effect of naltrexone and acamprosate in alcohol-dependent patients using genetic indicators. Addict Biol. 2009 Jul;14(3):328-37.