Details of the Drug Combination

General Information of Drug Combination (ID: DC23SSD)

• Drug Combination Name: Naloxone + Ramosetron
• Indication: Postoperative Nausea and Vomiting; Status: Phase 1 [1]
• Component Drugs:
  Naloxone (DM3FXMA): Small molecular drug
  Ramosetron (DMH7GN8): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Naloxone

Disease Entry	ICD 11	Status	REF
Narcotic depression	6A7Z	Approved	[2]
Pain	MG30-MG3Z	Approved	[3]
Pruritus	EC90	Phase 3	[4]
Respiratory depression	MD11.5	Phase 3	[5]
Opioid dependence	6C43.2Z	Phase 1	[5]

Naloxone Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Opioid receptor mu (MOP)	TTKWM86	OPRM_HUMAN	Antagonist	[10]

Naloxone Interacts with 10 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Renin (REN)	OT52GZR2	RENI_HUMAN	Increases Activity	[11]
Natriuretic peptides A (NPPA)	OTMQNTNX	ANF_HUMAN	Decreases Expression	[12]
Vasopressin-neurophysin 2-copeptin (AVP)	OTAVZ76K	NEU2_HUMAN	Decreases Secretion	[13]
Pro-opiomelanocortin (POMC)	OTV41F7T	COLI_HUMAN	Increases Expression	[14]
Lutropin subunit beta (LHB)	OT5GBOVJ	LSHB_HUMAN	Increases Expression	[15]
Prolactin (PRL)	OTWFQGX7	PRL_HUMAN	Affects Expression	[16]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Increases Response To Substance	[17]
Endoplasmic reticulum chaperone BiP (HSPA5)	OTFUIRAO	BIP_HUMAN	Increases Expression	[18]
Liver carboxylesterase 1 (CES1)	OT9L0LR8	EST1_HUMAN	Affects Binding	[19]
Interleukin-2 (IL2)	OTGI4NSA	IL2_HUMAN	Decreases Response To Substance	[20]

Indication(s) of Ramosetron

Disease Entry	ICD 11	Status	REF
Diarrhea-predominant irritable bowel syndrome	DD91.01	Approved	[6]
Nausea and vomiting	MD90	Approved	[7]
Irritable bowel syndrome	DD91.0	Phase 4	[8]

Ramosetron Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
5-HT 3 receptor (5HT3R)	TTNXLKE	NOUNIPROTAC	Modulator	[21]
5-HT receptor (5HTR)	TT85JO3	NOUNIPROTAC	Modulator	[22]

Ramosetron Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[23]

Ramosetron Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[24]

References

• [1] ClinicalTrials.gov (NCT02416115) Anti Emetic Efficacy of Combination of Ramosetron and Premixture of Naloxone With Patient-controlled Analgesia
• [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: 1668).
• [3] Naloxone FDA Label
• [4] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [5] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [6] Current and emerging pharmacological approaches for treating diarrhea-predominant irritable bowel syndrome. Expert Opin Pharmacother. 2020 Jan;21(1):63-71.
• [7] 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: 2301).
• [8] ClinicalTrials.gov (NCT01225237) A Study to Evaluate Efficacy of Ramosetron on Diarrhea-predominant Irritable Bowel Syndrome (IBS) in Male Patients. U.S. National Institutes of Health.
• [9] Customised in vitro model to detect human metabolism-dependent idiosyncratic drug-induced liver injury. Arch Toxicol. 2018 Jan;92(1):383-399. doi: 10.1007/s00204-017-2036-4. Epub 2017 Jul 31.
• [10] OxyContin abuse and overdose. Postgrad Med. 2009 Mar;121(2):163-7.
• [11] beta-Endorphin and essential hypertension: importance of the clonidine-naloxone interaction. Acta Physiol Hung. 1985;65(2):217-26.
• [12] Opioid peptides attenuate blood pressure increase in acute respiratory failure. Peptides. 2001 Apr;22(4):631-7. doi: 10.1016/s0196-9781(01)00373-4.
• [13] Blood pressure and vasopressin in progressive autonomic failure. Response to postural stimulation, L-dopa and naloxone. Brain. 1983 Jun;106 (Pt 2):503-11. doi: 10.1093/brain/106.2.503.
• [14] Endogenous opioids modulate the cardiovascular response to mental stress. Psychoneuroendocrinology. 1990;15(3):185-92. doi: 10.1016/0306-4530(90)90029-9.
• [15] Differences in the opioid control of luteinizing hormone secretion between pathological and iatrogenic hyperprolactinemic states. J Clin Endocrinol Metab. 1987 Mar;64(3):508-12. doi: 10.1210/jcem-64-3-508.
• [16] Influence of naloxone on muscle sympathetic nerve activity, systemic and calf haemodynamics and ambulatory blood pressure after exercise in mild essential hypertension. J Hypertens. 1995 Apr;13(4):447-61.
• [17] Central opioid inhibition of neuroendocrine stress responses in pregnancy in the rat is induced by the neurosteroid allopregnanolone. J Neurosci. 2009 May 20;29(20):6449-60. doi: 10.1523/JNEUROSCI.0708-09.2009.
• [18] Chronic oxycodone induces integrated stress response in rat brain. BMC Neurosci. 2015 Sep 16;16:58. doi: 10.1186/s12868-015-0197-8.
• [19] Human carboxylesterase 1: from drug metabolism to drug discovery. Biochem Soc Trans. 2003 Jun;31(Pt 3):620-4. doi: 10.1042/bst0310620.
• [20] Interleukin-2-induced antinociception in morphine-insensitive rats. Acta Pharmacol Sin. 2002 Nov;23(11):981-4.
• [21] Inhibitory effect of YM060 on 5-HT3 receptor-mediated depolarization in colonic myenteric neurons of the guinea pig. Eur J Pharmacol. 1995 Sep 5;283(1-3):107-12.
• [22] Natural products as sources of new drugs over the last 25 years. J Nat Prod. 2007 Mar;70(3):461-77.
• [23] Contribution of P-glycoprotein to efflux of ramosetron, a 5-HT3 receptor antagonist, across the blood-brain barrier. J Pharm Pharmacol. 2002 Aug;54(8):1055-63.
• [24] Ondansetron, ramosetron, or palonosetron: which is a better choice of antiemetic to prevent postoperative nausea and vomiting in patients undergoing laparoscopic cholecystectomy? Anesth Essays Res. 2011 Jul-Dec;5(2):182-6.