Details of the Drug Combination

General Information of Drug Combination (ID: DCMGJ5E)

• Drug Combination Name: Amisulpride + Bromocriptine
• Indication: Anorexia Nervosa; Status: Phase 1 [1]
• Component Drugs:
  Amisulpride (DMSJVAM): Small molecular drug
  Bromocriptine (DMVE3TK): Small molecular drug

Molecular Interaction Atlas of This Drug Combination

Indication(s) of Amisulpride

Disease Entry	ICD 11	Status	REF
Schizophrenia	6A20	Approved	[2]

Amisulpride 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]

Amisulpride Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[6]

Indication(s) of Bromocriptine

Disease Entry	ICD 11	Status	REF
Acromegaly	5A60.0	Approved	[3]
Hyperprolactinaemia	5A60.1	Approved	[3]
Parkinson disease	8A00.0	Approved	[4]
Postencephalitic Parkinson disease	N.A.	Approved	[3]

Bromocriptine Interacts with 1 DTT Molecule(s)

DTT Name	DTT ID	UniProt ID	Mode of Action	REF
Dopamine D2 receptor (D2R)	TTEX248	DRD2_HUMAN	Agonist	[7]

Bromocriptine Interacts with 1 DTP Molecule(s)

DTP Name	DTP ID	UniProt ID	Mode of Action	REF
P-glycoprotein 1 (ABCB1)	DTUGYRD	MDR1_HUMAN	Substrate	[8]

Bromocriptine Interacts with 1 DME Molecule(s)

DME Name	DME ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	DE4LYSA	CP3A4_HUMAN	Metabolism	[9]

Bromocriptine Interacts with 14 DOT Molecule(s)

DOT Name	DOT ID	UniProt ID	Mode of Action	REF
Cytochrome P450 3A4 (CYP3A4)	OTQGYY83	CP3A4_HUMAN	Affects Binding	[10]
D(2) dopamine receptor (DRD2)	OTBLXKEG	DRD2_HUMAN	Increases Response To Substance	[11]
Pro-opiomelanocortin (POMC)	OTV41F7T	COLI_HUMAN	Increases Expression	[12]
Follitropin subunit beta (FSHB)	OTGLS283	FSHB_HUMAN	Increases Expression	[13]
Lutropin subunit beta (LHB)	OT5GBOVJ	LSHB_HUMAN	Increases Expression	[13]
Prolactin (PRL)	OTWFQGX7	PRL_HUMAN	Decreases Expression	[14]
Somatotropin (GH1)	OT92RTRD	SOMA_HUMAN	Decreases Expression	[15]
Insulin (INS)	OTZ85PDU	INS_HUMAN	Decreases Expression	[16]
Cytochrome P450 1A1 (CYP1A1)	OTE4EFH8	CP1A1_HUMAN	Decreases Activity	[17]
Dopamine beta-hydroxylase (DBH)	OTC6I2SP	DOPO_HUMAN	Decreases Activity	[18]
Heme oxygenase 1 (HMOX1)	OTC1W6UX	HMOX1_HUMAN	Increases Expression	[19]
Cyclic AMP-dependent transcription factor ATF-3 (ATF3)	OTC1UOHP	ATF3_HUMAN	Increases Expression	[19]
Nuclear factor erythroid 2-related factor 2 (NFE2L2)	OT0HENJ5	NF2L2_HUMAN	Increases Localization	[19]
Cytochrome P450 1B1 (CYP1B1)	OTYXFLSD	CP1B1_HUMAN	Decreases Activity	[17]

References

• [1] ClinicalTrials.gov (NCT04128683) Dopamine Receptor Contributions to Prediction Error and Reversal Learning in Anorexia Nervosa
• [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: 963).
• [3] Bromocriptine 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: 35).
• [5] Mechanism of action of atypical antipsychotic drugs and the neurobiology of schizophrenia. CNS Drugs. 2006;20(5):389-409.
• [6] Identification of P-glycoprotein substrates and inhibitors among psychoactive compounds--implications for pharmacokinetics of selected substrates. J Pharm Pharmacol. 2004 Aug;56(8):967-75.
• [7] Silymarin BIO-C, an extract from Silybum marianum fruits, induces hyperprolactinemia in intact female rats. Phytomedicine. 2009 Sep;16(9):839-44.
• [8] Improving the prediction of the brain disposition for orally administered drugs using BDDCS. Adv Drug Deliv Rev. 2012 Jan;64(1):95-109.
• [9] Kinetics of dithionite-dependent reduction of cytochrome P450 3A4: heterogeneity of the enzyme caused by its oligomerization. Biochemistry. 2005 Oct 25;44(42):13902-13.
• [10] Mechanism of interactions of alpha-naphthoflavone with cytochrome P450 3A4 explored with an engineered enzyme bearing a fluorescent probe. Biochemistry. 2007 Jan 9;46(1):106-19. doi: 10.1021/bi061944p.
• [11] Imaging gene-substance interactions: the effect of the DRD2 TaqIA polymorphism and the dopamine agonist bromocriptine on the brain activation during the anticipation of reward. Neurosci Lett. 2006 Sep 25;405(3):196-201. doi: 10.1016/j.neulet.2006.07.030. Epub 2006 Aug 8.
• [12] Bromocriptine inhibits pro-opiomelanocortin mRNA and ACTH precursor secretion in small cell lung cancer cell lines. J Clin Invest. 1992 Sep;90(3):705-10. doi: 10.1172/JCI115941.
• [13] Resolution of hyperprolactinaemia after bromocriptine-induced pregnancy. Lancet. 1979 Apr 7;1(8119):784-5. doi: 10.1016/s0140-6736(79)91247-9.
• [14] Long-term follow-up of prolactinomas: normoprolactinemia after bromocriptine withdrawal. J Clin Endocrinol Metab. 2002 Aug;87(8):3578-82. doi: 10.1210/jcem.87.8.8722.
• [15] Improvement of congestive heart failure after octreotide and transsphenoidal surgery in a patient with acromegaly. Intern Med. 2009;48(9):697-700. doi: 10.2169/internalmedicine.48.1537. Epub 2009 May 1.
• [16] Activation of dopamine D2 receptors simultaneously ameliorates various metabolic features of obese women. Am J Physiol Endocrinol Metab. 2006 Nov;291(5):E1038-43. doi: 10.1152/ajpendo.00567.2005. Epub 2006 Jun 27.
• [17] Association of CYP1A1 and CYP1B1 inhibition in in vitro assays with drug-induced liver injury. J Toxicol Sci. 2021;46(4):167-176. doi: 10.2131/jts.46.167.
• [18] Plasma dopamine beta hydroxylase (D.B.H.) activity in Parkinsonian patients under L-dopa, and 2-bromo-alpha-ergocriptine loading. J Neural Transm. 1979;46(1):71-8. doi: 10.1007/BF01243430.
• [19] Bromocriptine methylate suppresses glial inflammation and moderates disease progression in a mouse model of amyotrophic lateral sclerosis. Exp Neurol. 2011 Nov;232(1):41-52. doi: 10.1016/j.expneurol.2011.08.001. Epub 2011 Aug 16.