Details of the Drug Combination

General Information of Drug Combination (ID: DC5HTF8)

• Drug Combination Name: Thiopental + Alfentanil
• Indication: Adverse Effect of Other General Anesthetics; Status: Phase 1 [1]
• Component Drugs:
  Thiopental (DMGP8AX): Small molecular drug
  Alfentanil (DMVO0UB): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Thiopental

Disease Entry	ICD 11	Status	REF
Anaesthesia	9A78.6	Approved	[2]
Epilepsy	8A60-8A68	Approved	[3]
Pseudotumor cerebri	N.A.	Approved	[3]

Thiopental Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Fatty acid amide hydrolase (FAAH)	TTDP1UC	NOUNIPROTAC	Inhibitor	[5]

Thiopental Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[6]

Thiopental Interacts with 7 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Angiotensinogen (AGT)	OTBZLYR3	ANGT_HUMAN	Increases Expression	[7]
Interleukin-2 receptor subunit alpha (IL2RA)	OT0MWCHG	IL2RA_HUMAN	Decreases Secretion	[8]
Heat shock protein beta-1 (HSPB1)	OTHFZ8ED	HSPB1_HUMAN	Increases Expression	[9]
Heat shock protein HSP 90-alpha (HSP90AA1)	OTLG1WPK	HS90A_HUMAN	Increases Expression	[9]
NF-kappa-B inhibitor alpha (NFKBIA)	OTFT924M	IKBA_HUMAN	Decreases Degradation	[10]
Caspase-3 (CASP3)	OTIJRBE7	CASP3_HUMAN	Increases Activity	[11]
Heat shock factor protein 1 (HSF1)	OTYNJ4KP	HSF1_HUMAN	Increases Activity	[9]

Indication(s) of Alfentanil

Disease Entry	ICD 11	Status	REF
Anaesthesia	9A78.6	Approved	[4]

Alfentanil Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Opioid receptor mu (MOP)	TTKWM86	OPRM_HUMAN	Agonist	[12]

Alfentanil Interacts with 3 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[13]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[14]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[15]

Alfentanil Interacts with 1 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
5-hydroxytryptamine receptor 3A (HTR3A)	OTAIV1AK	5HT3A_HUMAN	Affects Activity	[16]

References

• [1] ClinicalTrials.gov (NCT02486926) The Effects of Remifentanil and Remifentanil-Alfentanil Administration in Children
• [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: 2579).
• [3] Thiopental FDA Label
• [4] 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: 7108).
• [5] The general anesthetic propofol increases brain N-arachidonylethanolamine (anandamide) content and inhibits fatty acid amide hydrolase. Br J Pharmacol. 2003 Jul;139(5):1005-13.
• [6] Lerman J. (2014). Neonatal Anesthesia. Springer.
• [7] Ketamine hypertension and the renin-angiotensin system. Clin Exp Hypertens A. 1983;5(6):875-83. doi: 10.3109/10641968309081814.
• [8] Effects of different anaesthetic agents on immune cell function in vitro. Eur J Anaesthesiol. 2005 Aug;22(8):616-23. doi: 10.1017/s0265021505001031.
• [9] Thiopental protects human T lymphocytes from apoptosis in vitro via the expression of heat shock protein 70. J Pharmacol Exp Ther. 2008 Apr;325(1):217-25. doi: 10.1124/jpet.107.133108. Epub 2008 Jan 24.
• [10] Thiopental inhibits tumor necrosis factor alpha-induced activation of nuclear factor kappaB through suppression of kappaB kinase activity. Anesthesiology. 2003 Aug;99(2):360-7. doi: 10.1097/00000542-200308000-00017.
• [11] Thiopental-induced apoptosis in lymphocytes is independent of CD95 activation. Anesthesiology. 2005 Sep;103(3):576-84. doi: 10.1097/00000542-200509000-00021.
• [12] Concentration-effect relationship of intravenous alfentanil and ketamine on peripheral neurosensory thresholds, allodynia and hyperalgesia of neuropathic pain. Pain. 2001 Mar;91(1-2):177-87.
• [13] Pharmacogenetic determinants of human liver microsomal alfentanil metabolism and the role of cytochrome P450 3A5. Anesthesiology. 2005 Mar;102(3):550-6.
• [14] Influence of CYP3A5 genotype on the pharmacokinetics and pharmacodynamics of the cytochrome P4503A probes alfentanil and midazolam. Clin Pharmacol Ther. 2007 Oct;82(4):410-26.
• [15] Drug Interactions Flockhart Table
• [16] The effects of fentanyl-like opioids and hydromorphone on human 5-HT3A receptors. Anesth Analg. 2008 Jul;107(1):107-12. doi: 10.1213/ane.0b013e31817342c2.