Details of the Drug Combination

General Information of Drug Combination (ID: DC9DCHC)

• Drug Combination Name: Prochlorperazine + Ketorolac
• Indication: Migraine; Status: Phase 1 [1]
• Component Drugs:
  Prochlorperazine (DM53SRA): Small molecular drug
  Ketorolac (DMI4EL5): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Prochlorperazine

Disease Entry	ICD 11	Status	REF
Nausea	MD90	Approved	[2]

Prochlorperazine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Dopamine D2 receptor (D2R)	TTEX248	DRD2_HUMAN	Antagonist	[5]

Prochlorperazine Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[6]

Prochlorperazine Interacts with 2 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Transcription factor EB (TFEB)	OTJUJJQY	TFEB_HUMAN	Affects Localization	[7]
Glucose-6-phosphatase catalytic subunit 1 (G6PC1)	OTJ6FM9F	G6PC1_HUMAN	Increases ADR	[4]

Indication(s) of Ketorolac

Disease Entry	ICD 11	Status	REF
Postoperative inflammation	1A00-CA43.1	Approved	[3]

Ketorolac Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Prostaglandin G/H synthase (COX)	TTK0943	PGH1_HUMAN; PGH2_HUMAN	Inhibitor	[8]

Ketorolac Interacts with 2 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2C8 (CYP2C8)	DES5XRU	CP2C8_HUMAN	Metabolism	[9]
UDP-glucuronosyltransferase 2B7 (UGT2B7)	DEB3CV1	UD2B7_HUMAN	Metabolism	[9]

Ketorolac Interacts with 7 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Prostaglandin G/H synthase 1 (PTGS1)	OTHCRLEC	PGH1_HUMAN	Decreases Expression	[10]
Prostaglandin G/H synthase 2 (PTGS2)	OT75U9M4	PGH2_HUMAN	Increases Expression	[10]
HLA class I histocompatibility antigen, A alpha chain (HLA-A)	OTAH14LU	HLAA_HUMAN	Affects Expression	[11]
HLA class I histocompatibility antigen, alpha chain E (HLA-E)	OTX1CTFB	HLAE_HUMAN	Affects Expression	[11]
HLA class I histocompatibility antigen, alpha chain G (HLA-G)	OTMLK1KN	HLAG_HUMAN	Affects Expression	[11]
Hypoxia-inducible factor 1-alpha (HIF1A)	OTADSC03	HIF1A_HUMAN	Decreases Expression	[12]
Endothelial PAS domain-containing protein 1 (EPAS1)	OTRE3O8U	EPAS1_HUMAN	Decreases Expression	[12]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Headache, Migraine	DCCCD3W	N. A.	Phase 2	[13]

References

• [1] ClinicalTrials.gov (NCT06182098) Intravenous Fluids in Pediatric Migraine
• [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: 7279).
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services. 2015
• [4] 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.
• [5] In vitro and in vivo characteristics of prochlorperazine oral disintegrating film. Int J Pharm. 2009 Feb 23;368(1-2):98-102.
• [6] Potential for drug interactions involving cytochromes P450 2D6 and 3A4 on general adult psychiatric and functional elderly psychiatric wards. Br J Clin Pharmacol. 2004 Apr;57(4):464-72.
• [7] Rescue of Pink1 Deficiency by Stress-Dependent Activation of Autophagy. Cell Chem Biol. 2017 Apr 20;24(4):471-480.e4. doi: 10.1016/j.chembiol.2017.03.005. Epub 2017 Mar 30.
• [8] Cyclooxygenase and nitric oxide synthase dependence of cutaneous reactive hyperemia in humans. Am J Physiol Heart Circ Physiol. 2007 Jul;293(1):H425-32.
• [9] Body weight, gender and pregnancy affect enantiomer-specific ketorolac pharmacokinetics. Br J Clin Pharmacol. 2017 Sep;83(9):1966-1975.
• [10] Acetaminophen selectively suppresses peripheral prostaglandin E2 release and increases COX-2 gene expression in a clinical model of acute inflammation. Pain. 2007 Jun;129(3):279-86.
• [11] Systems pharmacological analysis of drugs inducing stevens-johnson syndrome and toxic epidermal necrolysis. Chem Res Toxicol. 2015 May 18;28(5):927-34. doi: 10.1021/tx5005248. Epub 2015 Apr 3.
• [12] Ibuprofen-mediated reduction of hypoxia-inducible factors HIF-1alpha and HIF-2alpha in prostate cancer cells. Clin Cancer Res. 2003 Aug 1;9(8):3150-7.
• [13] ClinicalTrials.gov (NCT06083571) Intranasal Ketorolac Trial