Details of the Drug Combination

General Information of Drug Combination (ID: DC3WH2F)

• Drug Combination Name: Haloperidol + Diphenhydramine
• Indication: Migraine Headaches; Status: Phase 4 [1]
• Component Drugs:
  Haloperidol (DM96SE0): Small molecular drug
  Diphenhydramine (DMKQTBA): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Haloperidol

Disease Entry	ICD 11	Status	REF
Delirium	N.A.	Approved	[2]
Nausea	MD90	Approved	[2]
Psychotic disorder	6A20-6A25	Approved	[2]
Schizophrenia	6A20	Approved	[3]
Vomiting	MD90	Approved	[2]
Coronavirus Disease 2019 (COVID-19)	1D6Y	Investigative	[4]
Tourette syndrome	8A05.00	Investigative	[2]

Haloperidol Interacts with 3 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Dopamine D2 receptor (D2R)	TTEX248	DRD2_HUMAN	Antagonist	[10]
HUMAN opioid receptor sigma 1 (OPRS1)	TTTPE1L	SGMR1_HUMAN	Modulator	[11]
HUMAN sigma intracellular receptor 2 (TMEM97)	TTIS0R2	SGMR2_HUMAN	Modulator	[11]

Haloperidol Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[12]

Haloperidol Interacts with 9 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[13]
Cytochrome P450 1A2 (CYP1A2)	DEJGDUW	CP1A2_HUMAN	Metabolism	[14]
Cytochrome P450 1A1 (CYP1A1)	DE6OQ3W	CP1A1_HUMAN	Metabolism	[14]
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[15]
Cytochrome P450 3A5 (CYP3A5)	DEIBDNY	CP3A5_HUMAN	Metabolism	[13]
Cytochrome P450 3A7 (CYP3A7)	DERD86B	CP3A7_HUMAN	Metabolism	[16]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[14]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[14]
UDP-glucuronosyltransferase 1A9 (UGT1A9)	DE85D2P	UD19_HUMAN	Metabolism	[17]

Haloperidol Interacts with 129 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2D6 (CYP2D6)	OTZJC802	CP2D6_HUMAN	Affects Response To Substance	[18]
ATP-dependent translocase ABCB1 (ABCB1)	OTEJROBO	MDR1_HUMAN	Decreases Expression	[19]
D(1A) dopamine receptor (DRD1)	OTLZPBT7	DRD1_HUMAN	Affects Activity	[20]
D(4) dopamine receptor (DRD4)	OTAJTO7N	DRD4_HUMAN	Affects Activity	[20]
Brain-derived neurotrophic factor (BDNF)	OTLGH7EW	BDNF_HUMAN	Increases Expression	[21]
D(3) dopamine receptor (DRD3)	OT0OFFKB	DRD3_HUMAN	Affects Binding	[22]
Superoxide dismutase (SOD1)	OT39TA1L	SODC_HUMAN	Increases ADR	[23]
Catalase (CAT)	OTHEBX9R	CATA_HUMAN	Increases ADR	[23]
G protein-activated inward rectifier potassium channel 1 (KCNJ3)	OTHQG16J	KCNJ3_HUMAN	Increases ADR	[23]
Glutathione S-transferase P (GSTP1)	OTLP0A0Y	GSTP1_HUMAN	Decreases Expression	[19]
Multidrug resistance-associated protein 1 (ABCC1)	OTGUN89S	MRP1_HUMAN	Decreases Expression	[19]
Stearoyl-CoA desaturase (SCD)	OTB1073G	SCD_HUMAN	Increases Expression	[24]
3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR)	OTRT3F3U	HMDH_HUMAN	Increases Expression	[24]
Fatty acid synthase (FASN)	OTFII9KG	FAS_HUMAN	Increases Expression	[24]
Hydroxymethylglutaryl-CoA synthase, cytoplasmic (HMGCS1)	OTCO26FV	HMCS1_HUMAN	Increases Expression	[24]
Lathosterol oxidase (SC5D)	OT41KMW4	SC5D_HUMAN	Increases Expression	[25]
Low-density lipoprotein receptor (LDLR)	OTH559LU	LDLR_HUMAN	Increases Expression	[25]
Nuclear protein 1 (NUPR1)	OT4FU8C0	NUPR1_HUMAN	Increases Expression	[7]
Alpha-1-antichymotrypsin (SERPINA3)	OT9BP2S0	AACT_HUMAN	Increases Expression	[7]
Asparagine synthetase (ASNS)	OT8R922G	ASNS_HUMAN	Decreases Expression	[7]
Inhibin beta E chain (INHBE)	OTOI2NYG	INHBE_HUMAN	Increases Expression	[7]
Transgelin (TAGLN)	OTAEZ0KP	TAGL_HUMAN	Decreases Expression	[7]
Nuclear receptor subfamily 0 group B member 2 (NR0B2)	OT7UVICX	NR0B2_HUMAN	Increases Expression	[7]
Lysophospholipase D GDPD3 (GDPD3)	OTOHM9QM	GDPD3_HUMAN	Increases Expression	[7]
Fibronectin type III domain-containing protein 4 (FNDC4)	OTOQK0WK	FNDC4_HUMAN	Increases Expression	[7]
Protein DEPP1 (DEPP1)	OTB36PHJ	DEPP1_HUMAN	Increases Expression	[7]
AP-3 complex subunit beta-1 (AP3B1)	OTYTIH5Q	AP3B1_HUMAN	Increases Expression	[8]
Importin subunit alpha-3 (KPNA4)	OTP0EX18	IMA3_HUMAN	Increases Expression	[8]
Branched-chain-amino-acid aminotransferase, mitochondrial (BCAT2)	OT8L6EGI	BCAT2_HUMAN	Decreases Expression	[8]
Transmembrane protease serine 2 (TMPRSS2)	OTN44YQ5	TMPS2_HUMAN	Increases Expression	[26]
Period circadian protein homolog 1 (PER1)	OTVQF3WX	PER1_HUMAN	Increases Expression	[27]
Kinesin heavy chain isoform 5C (KIF5C)	OT35570Y	KIF5C_HUMAN	Decreases Expression	[8]
Copine-3 (CPNE3)	OTCR3WG2	CPNE3_HUMAN	Decreases Expression	[8]
CCR4-NOT transcription complex subunit 3 (CNOT3)	OT4D5Z9L	CNOT3_HUMAN	Decreases Expression	[8]
Pyridoxal phosphate homeostasis protein (PLPBP)	OT9DZ8P6	PLPHP_HUMAN	Increases Expression	[8]
Prolactin (PRL)	OTWFQGX7	PRL_HUMAN	Increases Expression	[28]
Fatty acid-binding protein, heart (FABP3)	OT562DA1	FABPH_HUMAN	Increases Expression	[8]
Prothymosin alpha (PTMA)	OT2W4T1M	PTMA_HUMAN	Increases Expression	[8]
Corticoliberin (CRH)	OT2MOC4T	CRF_HUMAN	Decreases Expression	[29]
Profilin-1 (PFN1)	OTHTGA1H	PROF1_HUMAN	Increases Expression	[8]
Signal recognition particle receptor subunit alpha (SRPRA)	OT5NMYTY	SRPRA_HUMAN	Decreases Expression	[8]
Stromelysin-2 (MMP10)	OTJDWW8Q	MMP10_HUMAN	Decreases Expression	[8]
Glycogen phosphorylase, muscle form (PYGM)	OTWLVWTV	PYGM_HUMAN	Decreases Expression	[8]
Histidine--tRNA ligase, cytoplasmic (HARS1)	OTHOEOTS	HARS1_HUMAN	Increases Expression	[8]
Plastin-3 (PLS3)	OTYBM4PK	PLST_HUMAN	Decreases Expression	[8]
Glial fibrillary acidic protein (GFAP)	OTQ01ZAS	GFAP_HUMAN	Decreases Expression	[8]
Solute carrier family 2, facilitated glucose transporter member 4 (SLC2A4)	OTJZG0LD	GLUT4_HUMAN	Increases Expression	[30]
Ezrin (EZR)	OTHBPF1Z	EZRI_HUMAN	Decreases Expression	[8]
V-type proton ATPase subunit B, kidney isoform (ATP6V1B1)	OT8FQ7MN	VATB1_HUMAN	Decreases Expression	[8]
Probable ATP-dependent RNA helicase DDX5 (DDX5)	OTLS124U	DDX5_HUMAN	Decreases Expression	[8]
Vascular endothelial growth factor receptor 1 (FLT1)	OTT0OGYS	VGFR1_HUMAN	Decreases Expression	[8]
Protein-L-isoaspartate(D-aspartate) O-methyltransferase (PCMT1)	OTGYVSGU	PIMT_HUMAN	Decreases Expression	[8]
Cofilin-1 (CFL1)	OTT6D5MH	COF1_HUMAN	Increases Expression	[8]
Acetyl-CoA acetyltransferase, mitochondrial (ACAT1)	OTJC60Q7	THIL_HUMAN	Decreases Expression	[8]
5-hydroxytryptamine receptor 2A (HTR2A)	OTWXJX0M	5HT2A_HUMAN	Affects Binding	[31]
General transcription factor IIE subunit 1 (GTF2E1)	OTAG9V0I	T2EA_HUMAN	Decreases Expression	[8]
Stress-induced-phosphoprotein 1 (STIP1)	OT7TXLOX	STIP1_HUMAN	Decreases Expression	[8]
Catenin alpha-1 (CTNNA1)	OTFC725Z	CTNA1_HUMAN	Decreases Expression	[8]
Radixin (RDX)	OTNSYUN6	RADI_HUMAN	Decreases Expression	[8]
Vascular endothelial growth factor receptor 2 (KDR)	OT15797V	VGFR2_HUMAN	Increases Expression	[8]
Transgelin-2 (TAGLN2)	OTUXZGDQ	TAGL2_HUMAN	Decreases Expression	[8]
Lysosomal acid lipase/cholesteryl ester hydrolase (LIPA)	OTIOLNHE	LICH_HUMAN	Increases Expression	[8]
Pituitary adenylate cyclase-activating polypeptide type I receptor (ADCYAP1R1)	OTNBHULA	PACR_HUMAN	Affects Expression	[9]
Small ribosomal subunit protein eS27 (RPS27)	OTFXKY7P	RS27_HUMAN	Increases Expression	[8]
Cell surface glycoprotein MUC18 (MCAM)	OTT8XKGE	MUC18_HUMAN	Increases Expression	[8]
Vesicle-fusing ATPase (NSF)	OTKRJ2ZT	NSF_HUMAN	Decreases Expression	[8]
Serine--tRNA ligase, cytoplasmic (SARS1)	OTFKXQ1O	SYSC_HUMAN	Decreases Expression	[8]
Very long-chain specific acyl-CoA dehydrogenase, mitochondrial (ACADVL)	OT50L4XB	ACADV_HUMAN	Decreases Expression	[8]
Peroxisomal multifunctional enzyme type 2 (HSD17B4)	OT8733D7	DHB4_HUMAN	Decreases Expression	[8]
Delta-1-pyrroline-5-carboxylate synthase (ALDH18A1)	OT6W40XU	P5CS_HUMAN	Decreases Expression	[8]
Heterogeneous nuclear ribonucleoprotein K (HNRNPK)	OTNPRM8U	HNRPK_HUMAN	Decreases Expression	[8]
Small ribosomal subunit protein uS9 (RPS16)	OTVGZOB5	RS16_HUMAN	Decreases Expression	[8]
Large ribosomal subunit protein eL30 (RPL30)	OTLQVY1Z	RL30_HUMAN	Increases Expression	[8]
Microtubule-associated protein 1A (MAP1A)	OTHO8K43	MAP1A_HUMAN	Decreases Expression	[8]
Large ribosomal subunit protein eL19 (RPL19)	OT33LM66	RL19_HUMAN	Decreases Expression	[8]
Transcriptional activator protein Pur-alpha (PURA)	OT975ELW	PURA_HUMAN	Increases Expression	[8]
Protein Dr1 (DR1)	OTR081M4	NC2B_HUMAN	Decreases Expression	[8]
Synaptic vesicular amine transporter (SLC18A2)	OTUOMMM6	VMAT2_HUMAN	Affects Binding	[32]
Mitochondrial-processing peptidase subunit alpha (PMPCA)	OT5X1G9Q	MPPA_HUMAN	Increases Expression	[8]
Aspartyl/asparaginyl beta-hydroxylase (ASPH)	OT3KGDEE	ASPH_HUMAN	Increases Expression	[8]
Potassium voltage-gated channel subfamily H member 2 (KCNH2)	OTZX881H	KCNH2_HUMAN	Decreases Activity	[33]
Translation initiation factor eIF2B subunit epsilon (EIF2B5)	OTV3R4RB	EI2BE_HUMAN	Increases Expression	[8]
Transcription intermediary factor 1-beta (TRIM28)	OTE38OBF	TIF1B_HUMAN	Decreases Expression	[8]
Condensin complex subunit 2 (NCAPH)	OTXOS97C	CND2_HUMAN	Decreases Expression	[8]
Inorganic pyrophosphatase (PPA1)	OTHZK1QB	IPYR_HUMAN	Increases Expression	[8]
Reticulocalbin-1 (RCN1)	OT3JBGAG	RCN1_HUMAN	Decreases Expression	[8]
Splicing factor 3B subunit 4 (SF3B4)	OTGB9OR9	SF3B4_HUMAN	Decreases Expression	[8]
Disks large homolog 2 (DLG2)	OTQ3BD8U	DLG2_HUMAN	Increases Expression	[8]
Striated muscle preferentially expressed protein kinase (SPEG)	OTQXWJR4	SPEG_HUMAN	Increases Expression	[8]
Cryptochrome-1 (CRY1)	OTTGAJT0	CRY1_HUMAN	Decreases Expression	[27]
Histone H2A type 2-C (H2AC20)	OTEIVLM1	H2A2C_HUMAN	Increases Expression	[8]
Tau-tubulin kinase 1 (TTBK1)	OTYW316L	TTBK1_HUMAN	Increases Expression	[8]
Coiled-coil domain-containing protein 121 (CCDC121)	OTWZ4FTT	CC121_HUMAN	Increases Expression	[8]
Nucleoporin p54 (NUP54)	OTHOIRMG	NUP54_HUMAN	Decreases Expression	[8]
Retinol dehydrogenase 11 (RDH11)	OTIND43N	RDH11_HUMAN	Decreases Expression	[8]
Dynein axonemal heavy chain 3 (DNAH3)	OTD2JOKM	DYH3_HUMAN	Increases Expression	[8]
Pre-mRNA-splicing factor ATP-dependent RNA helicase PRP16 (DHX38)	OTBVB3W5	PRP16_HUMAN	Decreases Expression	[8]
Small ribosomal subunit protein mS31 (MRPS31)	OTB0OBWK	RT31_HUMAN	Increases Expression	[8]
AP-2 complex subunit mu (AP2M1)	OTQCOSFN	AP2M1_HUMAN	Increases Expression	[8]
Probable ATP-dependent RNA helicase DDX27 (DDX27)	OT64NCZ6	DDX27_HUMAN	Increases Expression	[8]
PDZ and LIM domain protein 5 (PDLIM5)	OTLQVV22	PDLI5_HUMAN	Decreases Expression	[8]
Kremen protein 1 (KREMEN1)	OTGJFSAC	KREM1_HUMAN	Increases Expression	[8]
KH domain-containing RNA-binding protein QKI (QKI)	OTTAUGLB	QKI_HUMAN	Increases Expression	[34]
Transcriptional regulator protein Pur-beta (PURB)	OTCDDKYB	PURB_HUMAN	Decreases Expression	[8]
Melanin-concentrating hormone receptor 1 (MCHR1)	OTT57EOE	MCHR1_HUMAN	Affects Binding	[35]
Transmembrane 9 superfamily member 2 (TM9SF2)	OTA0C202	TM9S2_HUMAN	Decreases Expression	[8]
COP9 signalosome complex subunit 4 (COPS4)	OTNK2KS1	CSN4_HUMAN	Decreases Expression	[8]
Histone H2A.J (H2AJ)	OTVA4XTW	H2AJ_HUMAN	Increases Expression	[8]
MKI67 FHA domain-interacting nucleolar phosphoprotein (NIFK)	OT20GHN3	MK67I_HUMAN	Decreases Expression	[8]
ATP-dependent DNA/RNA helicase DHX36 (DHX36)	OT8IGL9Y	DHX36_HUMAN	Decreases Expression	[8]
tRNA:m(4)X modification enzyme TRM13 homolog (TRMT13)	OT2H0MCE	TRM13_HUMAN	Decreases Expression	[8]
Tropomodulin-3 (TMOD3)	OTQPNSTH	TMOD3_HUMAN	Decreases Expression	[8]
Endoplasmic reticulum aminopeptidase 1 (ERAP1)	OT72S99B	ERAP1_HUMAN	Decreases Expression	[8]
Ribosome-binding protein 1 (RRBP1)	OT4ZTPTM	RRBP1_HUMAN	Decreases Expression	[8]
DnaJ homolog subfamily B member 11 (DNAJB11)	OTDDK2SY	DJB11_HUMAN	Increases Expression	[8]
Translocation protein SEC63 homolog (SEC63)	OT1ICPMK	SEC63_HUMAN	Increases Expression	[8]
Cysteine and histidine-rich domain-containing protein 1 (CHORDC1)	OT3W6F1U	CHRD1_HUMAN	Increases Expression	[8]
Unconventional myosin-Vb (MYO5B)	OTCKL3W3	MYO5B_HUMAN	Decreases Expression	[8]
Pre-mRNA-processing factor 19 (PRPF19)	OTQ1STV3	PRP19_HUMAN	Increases Expression	[8]
E3 ubiquitin-protein ligase PDZRN3 (PDZRN3)	OTQ891OS	PZRN3_HUMAN	Decreases Expression	[8]
DNA-binding protein SATB2 (SATB2)	OT2W80XC	SATB2_HUMAN	Decreases Expression	[8]
TRPM8 channel-associated factor 1 (TCAF1)	OTSQQ37P	TCAF1_HUMAN	Decreases Expression	[8]
Talin-2 (TLN2)	OT10QQBC	TLN2_HUMAN	Decreases Expression	[8]
Mitogen-activated protein kinase 14 (MAPK14)	OT5TCO3O	MK14_HUMAN	Increases ADR	[23]
Sodium-dependent serotonin transporter (SLC6A4)	OT6FGDLW	SC6A4_HUMAN	Increases ADR	[23]
Dysbindin (DTNBP1)	OT9UQT2S	DTBP1_HUMAN	Increases Response To Substance	[36]
NADH-ubiquinone oxidoreductase chain 1 (ND1)	OTCLGIXV	NU1M_HUMAN	Increases ADR	[23]
Mitogen-activated protein kinase 8 (MAPK8)	OTEREYS5	MK08_HUMAN	Increases ADR	[23]
Synaptosomal-associated protein 25 (SNAP25)	OTUIQ81Q	SNP25_HUMAN	Affects Response To Substance	[37]

Indication(s) of Diphenhydramine

Disease Entry	ICD 11	Status	REF
Hyperemesis gravidarum	N.A.	Approved	[5]
Insomnia	7A00-7A0Z	Approved	[5]
Meniere disease	AB31.0	Approved	[6]
Nausea	MD90	Approved	[5]
Seasonal allergic rhinitis	CA08.01	Approved	[5]
Vasomotor/allergic rhinitis	CA08	Approved	[5]
Vomiting	MD90	Approved	[5]

Diphenhydramine Interacts with 2 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Histamine N-methyltransferase (HNMT)	TT2B6EV	HNMT_HUMAN	Inhibitor	[38]
Histamine H1 receptor (H1R)	TTTIBOJ	HRH1_HUMAN	Antagonist	[39]

Diphenhydramine Interacts with 4 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 2D6 (CYP2D6)	DECB0K3	CP2D6_HUMAN	Metabolism	[40]
Cytochrome P450 2C9 (CYP2C9)	DE5IED8	CP2C9_HUMAN	Metabolism	[41]
Mephenytoin 4-hydroxylase (CYP2C19)	DEGTFWK	CP2CJ_HUMAN	Metabolism	[17]
Prostaglandin G/H synthase 1 (COX-1)	DE073H6	PGH1_HUMAN	Metabolism	[17]

Diphenhydramine Interacts with 10 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cholinesterase (BCHE)	OTOH3WQ9	CHLE_HUMAN	Decreases Activity	[42]
Proepiregulin (EREG)	OTRM4NQY	EREG_HUMAN	Decreases Expression	[43]
Interleukin-1 beta (IL1B)	OT0DWXXB	IL1B_HUMAN	Decreases Expression	[43]
Antileukoproteinase (SLPI)	OTUNFUU8	SLPI_HUMAN	Increases Expression	[43]
Interleukin-8 (CXCL8)	OTS7T5VH	IL8_HUMAN	Decreases Expression	[43]
Bone morphogenetic protein 6 (BMP6)	OT9WN536	BMP6_HUMAN	Decreases Expression	[43]
Prostaglandin G/H synthase 2 (PTGS2)	OT75U9M4	PGH2_HUMAN	Decreases Expression	[43]
Mitogen-activated protein kinase 8 (MAPK8)	OTEREYS5	MK08_HUMAN	Increases Activity	[44]
Interleukin-24 (IL24)	OT4VUWH1	IL24_HUMAN	Decreases Expression	[43]
Cystine/glutamate transporter (SLC7A11)	OTKJ6PXW	XCT_HUMAN	Decreases Expression	[43]

Test Results of This Drug Combination in Other Disease Systems

Indication	DrugCom ID	Cell Line	Status	REF
Headache, Migraine	DC6R690	N. A.	Phase 4	[45]

References

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