Details of the Drug-Related molecule(s) Interaction Atlas

General Information of Drug (ID: DMOL2Y0)

• Drug Name: 1-Dibenzo[b,f]oxepin-10-yl-4-methyl-piperazine Drug Info
• Synonyms: RMI 60947; CHEMBL89970; piperazine, 1-dibenz[b,f]oxepin-10-yl-4-methyl-; Piperazine, 1-dibenz(b,f)oxepin-10-yl-4-methyl-; BRN 0624016; 1-Dibenz(b,f)oxepin-10-yl-4-methylpiperazine; 22012-06-2; AC1L4PU3; 1-Dibenzo[b,f]oxepin-10-yl-4-methyl-piperazine; AC1Q70N4; CTK8D8624; DTXSID60176452; ZINC26648468; BDBM50028598; AKOS005065368; 11-(4-Methylpiperazino)dibenz[b,f]oxepin; LS-111456; 1-benzo[b][1]benzoxepin-5-yl-4-methylpiperazine; 5-23-02-00446 (Beilstein Handbook Reference)

Indication

Disease Entry	ICD 11	Status	REF
Discovery agent	N.A.	Investigative	[1]

• Cross-matching ID:
  PubChem CID: 210956
  CAS Number: CAS 22012-06-2
  TTD Drug ID: DMOL2Y0

Molecule-Related Drug Atlas

Drug(s) Targeting Dopamine D3 receptor (D3R)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Cariprazine	DMJYDVK	Bipolar disorder	6A60	Approved	[2]
Pramipexole	DMNMW9R	Parkinson disease	8A00.0	Approved	[3]
Ropinirole	DMA6S1D	Parkinson disease	8A00.0	Approved	[3]
CM-2395	DMASPWR	Schizophrenia	6A20	Phase 3	[4]
P2B-001	DM9PVHX	Parkinson disease	8A00.0	Phase 3	[5]
RP5063	DMKUE8O	Schizophrenia	6A20	Phase 2	[6]
ONC201	DMM5SCF	Endometrial cancer	2C76	Phase 2	[7]
TAK-906	DMBQD9H	Diabetic gastroparesis	DA41.00	Phase 2	[8]
GSK598809	DMGU05N	Drug abuse	6C4G.1Z	Phase 2	[9]
GSK618334	DMJPXZ4	Drug abuse	6C4G.1Z	Phase 1	[9]

Drug(s) Targeting Dopamine D1 receptor (D1R)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Phenyltoloxamine	DMKAEQW	Allergy	4A80-4A85	Approved	[10]
Pergolide	DM14MAE	Parkinson disease	8A00.0	Approved	[3]
Methylergonovine	DMBEX4O	Spontaneous abortion	JA00.0	Approved	[11]
Fenoldopam	DMFAOKP	Hypertension	BA00-BA04	Approved	[12]
Zicronapine	DMP8ESD	Schizophrenia	6A20	Phase 3	[13]
Ecopipam	DMS9R43	Cocaine addiction	6C45.2	Phase 3	[14]
DAS-431	DMM3BPL	Dementia	6D80-6D86	Phase 2	[15]
Dihydrexidine	DMACPQO	Psychotic disorder	6A20-6A25	Phase 1/2	[16]
Lu AF28996	DMY572G	Parkinson disease	8A00.0	Phase 1	[17]
BAM-1110	DMPMKUF	Parkinson disease	8A00.0	Discontinued in Phase 2	[18]

Drug(s) Targeting Dopamine D4 receptor (D4R)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Clozapine	DMFC71L	Schizophrenia	6A20	Approved	[3]
Phenyltoloxamine	DMKAEQW	Allergy	4A80-4A85	Approved	[10]
CM-2395	DMASPWR	Schizophrenia	6A20	Phase 3	[4]
RP5063	DMKUE8O	Schizophrenia	6A20	Phase 2	[6]
L-745,870	DMTGR25	Psychotic disorder	6A20-6A25	Phase 2	[19]
NGD 94-1	DMM1Y8F	Schizophrenia	6A20	Phase 1	[20]
ABT-724	DMDQVY4	Erectile dysfunction	HA01.1	Discontinued in Phase 2	[21]
Lu-35138	DMQ7A35	Psychotic disorder	6A20-6A25	Discontinued in Phase 2	[22]
NGD-94-4	DMZ9WLO	Schizophrenia	6A20	Discontinued in Phase 1	[23]
PD-165167	DMD0GB4	Schizophrenia	6A20	Preclinical	[20]

Drug(s) Targeting Dopamine D5 receptor (D5R)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Phenyltoloxamine	DMKAEQW	Allergy	4A80-4A85	Approved	[10]
LE-300	DMGJL16	Schizophrenia	6A20	Preclinical	[20]
ZD-3638	DM6M9GC	Schizophrenia	6A20	Terminated	[20]
GMC-283	DMT1RH6	Schizophrenia	6A20	Terminated	[20]
(+/-)-nantenine	DM0L3GE	Discovery agent	N.A.	Investigative	[24]
ISOCLOZAPINE	DM52CPU	Discovery agent	N.A.	Investigative	[1]
FLUMEZAPINE	DMW0HOG	Discovery agent	N.A.	Investigative	[25]
ISOLOXAPINE	DMH1BN4	Discovery agent	N.A.	Investigative	[26]
1-[3-(2-Benzyl-phenoxy)-propyl]-pyrrolidine	DMD2NXL	Discovery agent	N.A.	Investigative	[10]
STEPHOLIDINE	DMGMXQC	Discovery agent	N.A.	Investigative	[27]

Drug(s) Targeting Dopamine D2 receptor (D2R)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dopamine	DMPGUCF	Acromegaly	5A60.0	Approved	[28]
Haloperidol	DM96SE0	Delirium		Approved	[29]
Perphenazine	DMA4MRX	Schizophrenia	6A20	Approved	[30]
Perazine	DM2AOTZ	Psychotic disorder	6A20-6A25	Approved	[31]
Domperidone	DMBDPY0	Gastrointestinal disease	DE2Z	Approved	[32]
Levodopa	DMN3E57	Parkinson disease	8A00.0	Approved	[33]
Quetiapine	DM1N62C	Anorexia nervosa cachexia	6B80	Approved	[34]
Pimozide	DMW83TP	Schizophrenia	6A20	Approved	[35]
Chlorpromazine	DMBGZI3	Acute intermittent hepatic porphyria	5C58.11	Approved	[36]
Iloperidone	DM6AUFY	Schizophrenia	6A20	Approved	[37]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Dopamine D1 receptor (D1R)	TTZFYLI	DRD1_HUMAN	Inhibitor	[1]
Dopamine D2 receptor (D2R)	TTEX248	DRD2_HUMAN	Inhibitor	[1]
Dopamine D3 receptor (D3R)	TT4C8EA	DRD3_HUMAN	Inhibitor	[1]
Dopamine D4 receptor (D4R)	TTE0A2F	DRD4_HUMAN	Inhibitor	[1]
Dopamine D5 receptor (D5R)	TTS2PH3	DRD5_HUMAN	Inhibitor	[1]

References

• [1] Affinity of 10-(4-methylpiperazino)dibenz[b,f]oxepins for clozapine and spiroperidol binding sites in rat brain. J Med Chem. 1982 Jul;25(7):855-8.
• [2] Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
• [3] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [4] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031127)
• [5] Pharmacology of pramipexole, a dopamine D3-preferring agonist useful in treating Parkinson's disease. Clin Neuropharmacol. 1998 May-Jun;21(3):141-51.
• [6] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [7] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [8] Safety, Pharmacokinetics, and Pharmacodynamics of Trazpiroben (TAK-906), a Novel Selective D 2 /D 3 Receptor Antagonist: A Phase 1 Randomized, Placebo-Controlled Single- and Multiple-Dose Escalation Study in Healthy Participants. Clin Pharmacol Drug Dev. 2021 Jan 18.
• [9] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [10] Dopamine/serotonin receptor ligands. 9. Oxygen-containing midsized heterocyclic ring systems and nonrigidized analogues. A step toward dopamine D5 ... J Med Chem. 2004 Aug 12;47(17):4155-8.
• [11] Reinforcement in an in vitro analog of appetitive classical conditioning of feeding behavior in Aplysia: blockade by a dopamine antagonist. Learn Mem. 2005 May-Jun;12(3):216-20.
• [12] Etiology of iodinated radiocontrast nephrotoxicity and its attenuation by beraprost. Yakugaku Zasshi. 2008 Jul;128(7):1023-9.
• [13] Clinical pipeline report, company report or official report of Lundbeck.
• [14] A D1 receptor antagonist, ecopipam, for treatment of tics in Tourette syndrome.Clin Neuropharmacol.2014 Jan-Feb;37(1):26-30.
• [15] Adrogolide HCl (ABT-431; DAS-431), a prodrug of the dopamine D1 receptor agonist, A-86929: preclinical pharmacology and clinical data. CNS Drug Rev. 2001 Fall;7(3):305-16.
• [16] trans-2,3-dihydroxy-6a,7,8,12b-tetrahydro-6H-chromeno[3,4-c]isoquinoline: synthesis, resolution, and preliminary pharmacological characterization o... J Med Chem. 2006 Nov 16;49(23):6848-57.
• [17] Clinical pipeline report, company report or official report of Lundbeck
• [18] Therapeutic effects of dopamine D1/D2 receptor agonists on detrusor hyperreflexia in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned parkinso... J Pharmacol Exp Ther. 1998 Jul;286(1):228-33.
• [19] Dopamine D4 receptor involvement in the discriminative stimulus effects in rats of LSD, but not the phenethylamine hallucinogen DOI. Psychopharmacology (Berl). 2009 Apr;203(2):265-77.
• [20] The pipeline and future of drug development in schizophrenia. Mol Psychiatry. 2007 Oct;12(10):904-22.
• [21] Activation of dopamine D4 receptors by ABT-724 induces penile erection in rats. Proc Natl Acad Sci U S A. 2004 April 27; 101(17): 6758-6763.
• [22] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800014237)
• [23] I. NGD 94-1: identification of a novel, high-affinity antagonist at the human dopamine D4 receptor. J Pharmacol Exp Ther. 1997 Aug;282(2):1011-9.
• [24] Synthetic studies and pharmacological evaluations on the MDMA ('Ecstasy') antagonist nantenine. Bioorg Med Chem Lett. 2010 Jan 15;20(2):628-31.
• [25] Effects of conformationally restricted 4-piperazinyl-10H-thienobenzodiazepine neuroleptics on central dopaminergic and cholinergic systems. J Med Chem. 1982 Oct;25(10):1133-40.
• [26] Synthesis of clozapine analogues and their affinity for clozapine and spiroperidol binding sites in rat brain. J Med Chem. 1981 Sep;24(9):1021-6.
• [27] Dibenzazecine scaffold rebuilding--is the flexibility always essential for high dopamine receptor affinities Bioorg Med Chem. 2009 Oct 1;17(19):6898-907.
• [28] The Detection of Dopamine Gene Receptors (DRD1-DRD5) Expression on Human Peripheral Blood Lymphocytes by Real Time PCR. Iran J Allergy Asthma Immunol. 2004 Dec;3(4):169-74.
• [29] Dopaminergic synapses in the matrix of the ventrolateral striatum after chronic haloperidol treatment. Synapse. 2002 Aug;45(2):78-85.
• [30] CYP2D6 and DRD2 genes differentially impact pharmacodynamic sensitivity and time course of prolactin response to perphenazine. Pharmacogenet Genomics. 2007 Nov;17(11):989-93.
• [31] Synthesis and in vitro binding of N-phenyl piperazine analogs as potential dopamine D3 receptor ligands. Bioorg Med Chem. 2005 Jan 3;13(1):77-87.
• [32] Screening of domperidone in wastewater by high performance liquid chromatography and solid phase extraction methods. Talanta. 2006 Jan 15;68(3):928-31.
• [33] 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: 3639).
• [34] Receptor reserve-dependent properties of antipsychotics at human dopamine D2 receptors. Eur J Pharmacol. 2009 Apr 1;607(1-3):35-40.
• [35] [The benzamides tiapride, sulpiride, and amisulpride in treatment for Tourette's syndrome]. Nervenarzt. 2007 Mar;78(3):264, 266-8, 270-1.
• [36] Modulatory role of dopamine D2 receptors and fundamental role of L-type Ca2+ channels in the induction of long-term potentiation in the basolateral... Eur J Pharmacol. 2009 Mar 15;606(1-3):90-3.
• [37] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.