Details of the Drug Combination

General Information of Drug Combination (ID: DC74HF4)

• Drug Combination Name: Alprazolam + [3H]GABA
• Indication: Type 1 Diabetes Mellitus; Status: Phase 1 [1]
• Component Drugs:
  Alprazolam (DMC7XDN): Small molecular drug
  [3H]GABA (DMH24GL): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Alprazolam

Disease Entry	ICD 11	Status	REF
Anxiety	N.A.	Approved	[2]
Anxiety disorder	6B00-6B0Z	Approved	[3]
Panic disorder	6B01	Approved	[2]
Epilepsy	8A60-8A68	Phase 2	[4]
Mixed anxiety and depressive disorder	N.A.	Investigative	[2]

Alprazolam Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Translocator protein (TSPO)	TTPTXIN	TSPO_HUMAN	Agonist	[6]

Alprazolam Interacts with 4 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[7]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[8]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[9]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[10]

Alprazolam Interacts with 5 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A5 (CYP3A5)	OTSXFBXB	CP3A5_HUMAN	Increases Hydroxylation	[8]
Translocator protein (TSPO)	OTSU7ESK	TSPO_HUMAN	Increases ADR	[11]
Lutropin subunit beta (LHB)	OT5GBOVJ	LSHB_HUMAN	Increases Secretion	[12]
Platelet-activating factor receptor (PTAFR)	OT2133DF	PTAFR_HUMAN	Increases ADR	[11]
Peptidyl-prolyl cis-trans isomerase A (PPIA)	OTHJMWQQ	PPIA_HUMAN	Increases Hydroxylation	[13]

Indication(s) of [3H]GABA

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[5]

References

• [1] ClinicalTrials.gov (NCT03635437) Evaluation of Safety and Diabetes Status Upon Oral Treatment With GABA in Patients With Longstanding Type-1 Diabetes
• [2] Alprazolam 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: 7111).
• [4] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [5] 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: 5410).
• [6] Comparison of five benzodiazepine-receptor agonists on buprenorphine-induced mu-opioid receptor regulation. J Pharmacol Sci. 2009 May;110(1):36-46.
• [7] No relevant interaction with alprazolam, caffeine, tolbutamide, and digoxin by treatment with a low-hyperforin St John's wort extract. Planta Med. 2005 Apr;71(4):331-7.
• [8] Identification and phenotype characterization of two CYP3A haplotypes causing different enzymatic capacity in fetal livers. Clin Pharmacol Ther. 2005 Apr;77(4):259-70.
• [9] Drug Interactions Flockhart Table
• [10] Substrates, inducers, inhibitors and structure-activity relationships of human Cytochrome P450 2C9 and implications in drug development. Curr Med Chem. 2009;16(27):3480-675.
• [11] ADReCS-Target: target profiles for aiding drug safety research and application. Nucleic Acids Res. 2018 Jan 4;46(D1):D911-D917. doi: 10.1093/nar/gkx899.
• [12] The effect of alprazolam on serum cortisol and luteinizing hormone pulsatility in normal women and in women with stress-related anovulation. J Clin Endocrinol Metab. 1995 Mar;80(3):818-23. doi: 10.1210/jcem.80.3.7883836.
• [13] Alprazolam as a probe for CYP3A using a single blood sample: pharmacokinetics of parent drug, and of alpha- and 4-hydroxy metabolites in healthy subjects. Eur J Clin Pharmacol. 2005 Apr;61(2):113-8.