General Information of Drug Combination (ID: DCTYZ84)

Drug Combination Name
Sildenafil Tramadol
Indication
Disease Entry Status REF
Premature Ejaculation Phase 4 [1]
Component Drugs Sildenafil   DM4YDAJ Tramadol   DMRQD04
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 Sildenafil
Disease Entry ICD 11 Status REF
Alveolar capillary dysplasia with misalignment of pulmonary veins N.A. Approved [2]
Erectile dysfunction HA01.1 Approved [3]
Coronavirus Disease 2019 (COVID-19) 1D6Y Phase 3 [4]
Respiratory failure CB41 Investigative [2]
Sildenafil Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
HUMAN phosphodiesterase type 5 (PDE5) TTRYFSB PDE5A_HUMAN Inhibitor [7]
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Sildenafil Interacts with 2 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-3 (GNB3) OTA6HYBA GBB3_HUMAN Increases Response [8]
Angiotensin-converting enzyme (ACE) OTDF1964 ACE_HUMAN Increases Response [9]
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Indication(s) of Tramadol
Disease Entry ICD 11 Status REF
Osteoarthritis FA00-FA05 Approved [5]
Pain MG30-MG3Z Approved [6]
Chronic pain MG30 Investigative [5]
Premature ejaculation HA03.0Z Investigative [5]
Tramadol Interacts with 1 DTT Molecule(s)
DTT Name DTT ID UniProt ID Mode of Action REF
5-HT 2C receptor (HTR2C) TTWJBZ5 5HT2C_HUMAN Modulator [10]
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Tramadol Interacts with 1 DTP Molecule(s)
DTP Name DTP ID UniProt ID Mode of Action REF
P-glycoprotein 1 (ABCB1) DTUGYRD MDR1_HUMAN Substrate [11]
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Tramadol Interacts with 4 DME Molecule(s)
DME Name DME ID UniProt ID Mode of Action REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Metabolism [12]
UDP-glucuronosyltransferase 1A1 (UGT1A1) DEYGVN4 UD11_HUMAN Metabolism [13]
Cytochrome P450 2D6 (CYP2D6) DECB0K3 CP2D6_HUMAN Metabolism [12]
Cytochrome P450 2B6 (CYP2B6) DEPKLMQ CP2B6_HUMAN Metabolism [12]
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Tramadol Interacts with 6 DOT Molecule(s)
DOT Name DOT ID UniProt ID Mode of Action REF
Steroid 17-alpha-hydroxylase/17,20 lyase (CYP17A1) OTZKVLVJ CP17A_HUMAN Decreases Activity [14]
L-lactate dehydrogenase A chain (LDHA) OTN7K4XB LDHA_HUMAN Decreases Expression [15]
Creatine kinase B-type (CKB) OTUCKOTT KCRB_HUMAN Decreases Expression [15]
NADH-ubiquinone oxidoreductase 75 kDa subunit, mitochondrial (NDUFS1) OTTIZDFR NDUS1_HUMAN Decreases Expression [15]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Affects Activity [15]
kinase isozyme 3, mitochondrial (PDK3) OTCPSTID PDK3_HUMAN Increases Expression [15]
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⏷ Show the Full List of 6 DOT(s)

References

1 ClinicalTrials.gov (NCT05183334) Combined On-demand Sildenafil Citrate and Tramadol Hydrochloride for Treatment of Premature Ejaculation
2 Sildenafil FDA Label
3 FDA Approved Drug Products from FDA Official Website. 2019. Application Number: (ANDA) 206401.
4 ClinicalTrials.gov (NCT04304313) A Pilot Study of Sildenafil in COVID-19. U.S. National Institutes of Health.
5 Tramadol 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: 8286).
7 Nitric oxide inhibits the replication cycle of severe acute respiratory syndrome coronavirus. J Virol. 2005 Feb;79(3):1966-9. doi: 10.1128/JVI.79.3.1966-1969.2005.
8 Sildenafil response is influenced by the G protein beta 3 subunit GNB3 C825T polymorphism: a pilot study. J Urol. 2003 Mar;169(3):1048-51. doi: 10.1097/01.ju.0000058369.72348.ba.
9 ACE gene I/D and NOS3 G894T polymorphisms and response to sildenafil in men with erectile dysfunction. Urology. 2003 Jul;62(1):152-7. doi: 10.1016/s0090-4295(03)00137-7.
10 The inhibitory effects of tramadol on 5-hydroxytryptamine type 2C receptors expressed in Xenopus oocytes. Anesth Analg. 2004 May;98(5):1401-6, table of contents.
11 Tramadol hydrochloride: pharmacokinetics, pharmacodynamics, adverse side effects, co-administration of drugs and new drug delivery systems. Biomed Pharmacother. 2015 Mar;70:234-8.
12 Clinical pharmacology of tramadol. Clin Pharmacokinet. 2004;43(13):879-923.
13 Drug-drug interactions for UDP-glucuronosyltransferase substrates: a pharmacokinetic explanation for typically observed low exposure (AUCi/AUC) ratios. Drug Metab Dispos. 2004 Nov;32(11):1201-8.
14 Steroidogenic disruptive effects of the serotonin-noradrenaline reuptake inhibitors duloxetine, venlafaxine and tramadol in the H295R cell assay and in a recombinant CYP17 assay. Toxicol In Vitro. 2018 Mar;47:63-71.
15 Comparative study of the neurotoxicological effects of tramadol and tapentadol in SH-SY5Y cells. Toxicology. 2016 Jun 1;359-360:1-10. doi: 10.1016/j.tox.2016.06.010. Epub 2016 Jun 15.