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

General Information of Drug (ID: DMRHCEG)

• Drug Name: BMY-7378 Drug Info
• Synonyms: Bmy-7378; UNII-08EI0K81OL; CHEMBL13647; 08EI0K81OL; 8-(2-[4-(2-Methoxyphenyl)-1-piperazinyl]ethyl)-8-azaspiro[4.5]decane-7,9-dione; BMY7378; 8-(2-(4-(2-Methoxyphenyl)-1-piperazinyl)ethyl)-8-azaspiro(4.5)decane-7,9-dione; 21102-94-3; 8-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-8-azaspiro[4.5]decane-7,9-dione; 8-(2-(4-(2-methoxyphenyl)piperazin-1-yl)ethyl)-8-azaspiro[4.5]decane-7,9-dione; 8-[2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]-8-azaspiro[4.5]decane-7,9-dione; 8-Azaspiro(4.5)decane-7,9-dione, 8-(2-(4-(2-methox
• Cross-matching ID:
  PubChem CID: 2419
  ChEBI ID: CHEBI:92539
  CAS Number: CAS 21102-94-3
  TTD Drug ID: DMRHCEG

Molecule-Related Drug Atlas

Drug(s) Targeting Adrenergic receptor alpha-1B (ADRA1B)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Methamphetamine	DMPM4SK	Anxiety		Approved	[4]
Propericiazine	DME9JNL	Psychiatric disorder	6E8Z	Approved	[5]
Methoxamine	DMF5XQH	Hypertension	BA00-BA04	Approved	[6]
Phendimetrazine	DM6TS1N	Obesity	5B81	Approved	[7]
MEDETOMIDINE	DMX9Y7V	Pain	MG30-MG3Z	Phase 2	[8]
TIOSPIRONE	DME5QDP	N. A.	N. A.	Discontinued in Phase 3	[9]
Sunepitron	DM6M8ZX	N. A.	N. A.	Discontinued in Phase 3	[10]
MAZAPERTINE	DMRHYAU	N. A.	N. A.	Discontinued in Phase 2	[11]
SOU-001	DMPAEK5	Urinary incontinence	MF50.2	Discontinued in Phase 2	[12]
SNAP-5089	DMROJEN	Heart arrhythmia	BC65	Terminated	[13]

Drug(s) Targeting Adrenergic receptor alpha-1D (ADRA1D)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Doxazosin	DM9PLRH	Benign prostatic hyperplasia	GA90	Approved	[14]
Armodafinil	DMGB035	Malignant glioma	2A00.0	Approved	[15]
Alfuzosin	DMZVMKF	Benign prostatic hyperplasia	GA90	Approved	[16]
Moxisylyte	DMFCLYW	Erectile dysfunction	HA01.1	Approved	[17]
Terazosin	DM3JCVS	Benign prostatic hyperplasia	GA90	Approved	[18]
Bunazosin	DM4I8O7	Glaucoma/ocular hypertension	9C61	Approved	[19]
Trimazosin	DM1QLST	Congestive heart failure	BD10	Approved	[20]
MEDETOMIDINE	DMX9Y7V	Pain	MG30-MG3Z	Phase 2	[8]
DL-017	DMM8GZT	Hypertension	BA00-BA04	Phase 1	[21]
PMID30124346-Compound-LDT8	DM5MUNG	Benign prostatic hyperplasia	GA90	Patented	[22]

Drug(s) Targeting 5-HT 1A receptor (HTR1A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Trazodone	DMK1GBJ	Depression	6A70-6A7Z	Approved	[23]
Buspirone	DMBS632	Anxiety disorder	6B00-6B0Z	Approved	[24]
OPC-34712	DMHG57U	Major depressive disorder	6A70.3	Approved	[25]
Vilazodone	DM4LECQ	Major depressive disorder	6A70.3	Approved	[26]
Flibanserin	DM70DTN	Depression	6A70-6A7Z	Approved	[27]
Gepirone	DMGX5Q0	Major depressive disorder	6A70.3	Approved	[28]
TERTATOLOL	DM2L3D5	Hypertension	BA00-BA04	Approved	[29]
Urapidil	DMD59GI	Hypertension	BA00-BA04	Approved	[30]
Treximet	DMU54QB	Migraine	8A80	Approved	[31]
CM-2395	DMASPWR	Schizophrenia	6A20	Phase 3	[32]

Drug(s) Targeting Adrenergic receptor alpha-1A (ADRA1A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
SILODOSIN	DMJSBT6	Benign prostatic hyperplasia	GA90	Approved	[33]
NAFTOPIDIL	DMQ8R4E	Hypertension	BA00-BA04	Approved	[33]
Tamsulosin	DM5QF9V	Benign prostatic hyperplasia	GA90	Approved	[23]
Xatral	DMLHOA0	Benign prostatic hyperplasia	GA90	Approved	[34]
Dutasteride + tamsulosin	DM6P8HU	Benign prostatic hyperplasia	GA90	Phase 3	[31]
Besipirdine	DMLVNTA	Cognitive impairment	6D71	Phase 3	[35]
MEDETOMIDINE	DMX9Y7V	Pain	MG30-MG3Z	Phase 2	[8]
PMID30124346-Compound-LDT8	DM5MUNG	Benign prostatic hyperplasia	GA90	Patented	[22]
PMID30124346-Compound-LDT66	DMJMTNL	Benign prostatic hyperplasia	GA90	Patented	[22]
TIOSPIRONE	DME5QDP	N. A.	N. A.	Discontinued in Phase 3	[9]

Drug(s) Affected By Alpha-1D adrenergic receptor (ADRA1D)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Alfuzosin	DMZVMKF	Benign prostatic hyperplasia	GA90	Approved	[36]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[37]
Epinephrine	DM3KJBC	Acute asthma	CA23	Approved	[38]
Oxymetazoline	DM8ZXT6	Arrhythmia	BC9Z	Approved	[39]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[40]
Terbutaline	DMD4381	Asthma	CA23	Approved	[41]
Methoxamine	DMF5XQH	Hypertension	BA00-BA04	Approved	[39]
Quinidine	DMLPICK	N. A.	N. A.	Approved	[37]
Dexamethasone	DMMWZET	Acute adrenal insufficiency		Approved	[41]
Norepinephrine	DMOUC09	Alopecia	ED70	Approved	[39]

Drug(s) Affected By Alpha-1B adrenergic receptor (ADRA1B)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[37]
Epinephrine	DM3KJBC	Acute asthma	CA23	Approved	[38]
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[42]
Calcitriol	DM8ZVJ7	Congenital alopecia	LC30	Approved	[43]
Oxymetazoline	DM8ZXT6	Arrhythmia	BC9Z	Approved	[44]
Terbutaline	DMD4381	Asthma	CA23	Approved	[41]
Quinidine	DMLPICK	N. A.	N. A.	Approved	[37]
Dexamethasone	DMMWZET	Acute adrenal insufficiency		Approved	[41]
Cisplatin	DMRHGI9	Adenocarcinoma	2D40	Approved	[45]
Arsenic	DMTL2Y1	N. A.	N. A.	Approved	[46]

Drug(s) Affected By Alpha-1A adrenergic receptor (ADRA1A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tamsulosin	DM5QF9V	Benign prostatic hyperplasia	GA90	Approved	[47]
SILODOSIN	DMJSBT6	Benign prostatic hyperplasia	GA90	Approved	[38]
Gabapentin	DM6T924	Complex partial seizure	8A68.0	Approved	[48]
Verapamil	DMA7PEW	Angina pectoris	BA40	Approved	[37]
Epinephrine	DM3KJBC	Acute asthma	CA23	Approved	[38]
Troglitazone	DM3VFPD	Diabetic complication	5A2Y	Approved	[49]
Oxymetazoline	DM8ZXT6	Arrhythmia	BC9Z	Approved	[47]
Ciclosporin	DMAZJFX	Graft-versus-host disease	4B24	Approved	[50]
Quinidine	DMLPICK	N. A.	N. A.	Approved	[37]
Norepinephrine	DMOUC09	Alopecia	ED70	Approved	[36]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
5-HT 1A receptor (HTR1A)	TTSQIFT	5HT1A_HUMAN	Inhibitor	[1]
Adrenergic receptor alpha-1A (ADRA1A)	TTNGILX	ADA1A_HUMAN	Inhibitor	[2]
Adrenergic receptor alpha-1B (ADRA1B)	TTBRKXS	ADA1B_HUMAN	Inhibitor	[2]
Adrenergic receptor alpha-1D (ADRA1D)	TT34BHT	ADA1D_HUMAN	Inhibitor	[2]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Alpha-1A adrenergic receptor (ADRA1A)	OTUIWCL5	ADA1A_HUMAN	Protein Interaction/Cellular Processes	[3]
Alpha-1B adrenergic receptor (ADRA1B)	OTSAYAFD	ADA1B_HUMAN	Protein Interaction/Cellular Processes	[3]
Alpha-1D adrenergic receptor (ADRA1D)	OTW2CD1O	ADA1D_HUMAN	Protein Interaction/Cellular Processes	[3]

References

• [1] 8-[4-[2-(1,2,3,4-Tetrahydroisoquinolinyl]butyl-8-azaspiro[4.5]decane-7,9-dione: a new 5-HT1A receptor ligand with the same activity profile as busp... J Med Chem. 1996 Mar 1;39(5):1125-9.
• [2] Synthesis and structure-activity relationship of fluoro analogues of 8-{2-[4-(4-methoxyphenyl)piperazin-1yl]ethyl}-8-azaspiro[4.5]decane-7,9-dione ... J Med Chem. 2005 Apr 21;48(8):3076-9.
• [3] Heterodimers of alpha1B- and alpha1D-adrenergic receptors form a single functional entity. Mol Pharmacol. 2006 Jan;69(1):45-55. doi: 10.1124/mol.105.014985. Epub 2005 Sep 29.
• [4] Mirtazapine treatment after conditioning with methamphetamine alters subsequent expression of place preference. Drug Alcohol Depend. 2009 Jan 1;99(1-3):231-9.
• [5] Interaction of neuroleptics and antidepressants with rat brain alpha 2-receptors: a possible relationship between alpha 2-receptor antagonism and antidepressant action. Biol Psychiatry. 1984 Sep;19(9):1283-91.
• [6] Activation of alpha1-adrenoceptors inhibits growth hormone secretion in humans. Exp Clin Endocrinol Diabetes. 2009 Oct;117(9):460-2.
• [7] Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34.
• [8] A structure-activity relationship study of benzylic modifications of 4-[1-(1-naphthyl)ethyl]-1H-imidazoles on alpha 1- and alpha 2-adrenergic recep... J Med Chem. 1994 Jul 22;37(15):2328-33.
• [9] 3-Benzisothiazolylpiperazine derivatives as potential atypical antipsychotic agents. J Med Chem. 1996 Jan 5;39(1):143-8.
• [10] An integrated in silico 3D model-driven discovery of a novel, potent, and selective amidosulfonamide 5-HT1A agonist (PRX-00023) for the treatment o... J Med Chem. 2006 Jun 1;49(11):3116-35.
• [11] A new arylpiperazine antipsychotic with high D2/D3/5-HT1A/alpha 1A-adrenergic affinity and a low potential for extrapyramidal effects. J Med Chem. 1994 Apr 15;37(8):1060-2.
• [12] Drug repositioning: identifying and developing new uses for existing drugs. Nat Rev Drug Discov. 2004 Aug;3(8):673-83.
• [13] Alpha- and beta-adrenoceptors: from the gene to the clinic. 2. Structure-activity relationships and therapeutic applications. J Med Chem. 1995 Sep 15;38(19):3681-716.
• [14] The role of combination medical therapy in benign prostatic hyperplasia. Int J Impot Res. 2008 Dec;20 Suppl 3:S33-43.
• [15] Mechanisms of modafinil: A review of current research. Neuropsychiatr Dis Treat. 2007 June; 3(3): 349-364.
• [16] Alfuzosin: a review of the therapeutic use of the prolonged-release formulation given once daily in the management of benign prostatic hyperplasia. Drugs. 2002;62(4):633-53.
• [17] Pharmacokinetics of moxisylyte in healthy volunteers after intracavernous injection of increasing doses. Eur J Clin Pharmacol. 1996;49(5):411-5.
• [18] Induction of prostate apoptosis by alpha1-adrenoceptor antagonists: mechanistic significance of the quinazoline component. Prostate Cancer Prostatic Dis. 2002;5(2):88-95.
• [19] Bunazosin, a selective alpha1-adrenoceptor antagonist, as an anti-glaucoma drug: effects on ocular circulation and retinal neuronal damage. Cardiovasc Drug Rev. 2005 Spring;23(1):43-56.
• [20] The hypotensive effect of trimazosin is not caused solely by alpha 1-adrenoceptor blockade. J Cardiovasc Pharmacol. 1984 Jan-Feb;6(1):142-50.
• [21] Antihypertensive action and blockade of alpha1-adrenoceptors by DL-017, a quinazoline derivative. J Cardiovasc Pharmacol. 2001 Dec;38(6):893-9.
• [22] 5-HT1A receptor ligands and their therapeutic applications: review of new patents.Expert Opin Ther Pat. 2018 Sep;28(9):679-689.
• [23] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [24] Interactions between corticotropin-releasing hormone and serotonin: implications for the aetiology and treatment of anxiety disorders. Handb Exp Pharmacol. 2005;(169):181-204.
• [25] Effects of brexpiprazole, a novel serotonin-dopamine activity modulator, on phencyclidine-induced cognitive deficits in mice: a role for serotonin 5-HT1A receptors.Pharmacol Biochem Behav.2014 Sep;124:245-9.
• [26] 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
• [27] Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
• [28] Novel drugs and therapeutic targets for severe mood disorders. Neuropsychopharmacology. 2008 Aug;33(9):2080-92.
• [29] Synthesis of new derivatives of 8-OH-DPAT: Influence of substitution on the aromatic ring on the pharmacological profile, Bioorg. Med. Chem. Lett. 3(10):2035-2038 (1993).
• [30] Urapidil. A reappraisal of its use in the management of hypertension. Drugs. 1998 Nov;56(5):929-55.
• [31] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [32] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031127)
• [33] Pharmacophore identification of alpha(1A)-adrenoceptor antagonists. Bioorg Med Chem Lett. 2005 Feb 1;15(3):657-64.
• [34] Pharma & Vaccines. Product Development Pipeline. April 29 2009.
• [35] Alpha-Adrenergic activity and cardiovascular effects of besipirdine HCl (HP 749) and metabolite P7480 in vitro and in the conscious rat and dog. J Pharmacol Exp Ther. 1997 Apr;281(1):337-46.
• [36] The alpha 1-adrenergic receptor that mediates smooth muscle contraction in human prostate has the pharmacological properties of the cloned human alpha 1c subtype. Mol Pharmacol. 1994 Apr;45(4):703-8.
• [37] Effects of quinidine and verapamil on human cardiovascular alpha1-adrenoceptors. Circulation. 1998 Apr 7;97(13):1227-30. doi: 10.1161/01.cir.97.13.1227.
• [38] Carvedilol selectively inhibits oscillatory intracellular calcium changes evoked by human alpha1D- and alpha1B-adrenergic receptors. Cardiovasc Res. 2004 Sep 1;63(4):662-72. doi: 10.1016/j.cardiores.2004.05.014.
• [39] Chromatography studies on bio-affinity of nine ligands of alpha1-adrenoceptor to alpha1D subtypes overexpressed in cell membrane. Sci China C Life Sci. 2004 Aug;47(4):376-81. doi: 10.1360/03yc0109.
• [40] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [41] Neuroendocrine mediators up-regulate alpha1b- and alpha1d-adrenergic receptor subtypes in human monocytes. J Neuroimmunol. 1999 Mar 1;95(1-2):165-73. doi: 10.1016/s0165-5728(99)00011-9.
• [42] Retinoic acid receptor alpha amplifications and retinoic acid sensitivity in breast cancers. Clin Breast Cancer. 2013 Oct;13(5):401-8.
• [43] Large-scale in silico and microarray-based identification of direct 1,25-dihydroxyvitamin D3 target genes. Mol Endocrinol. 2005 Nov;19(11):2685-95.
• [44] Alpha-adrenoceptor agonistic activity of oxymetazoline and xylometazoline. Fundam Clin Pharmacol. 2010 Dec;24(6):729-39.
• [45] Activation of AIFM2 enhances apoptosis of human lung cancer cells undergoing toxicological stress. Toxicol Lett. 2016 Sep 6;258:227-236.
• [46] Prenatal arsenic exposure and the epigenome: identifying sites of 5-methylcytosine alterations that predict functional changes in gene expression in newborn cord blood and subsequent birth outcomes. Toxicol Sci. 2015 Jan;143(1):97-106. doi: 10.1093/toxsci/kfu210. Epub 2014 Oct 10.
• [47] Cell membrane chromatography competitive binding analysis for characterization of 1A adrenoreceptor binding interactions. Anal Bioanal Chem. 2011 Jul;400(10):3625-33. doi: 10.1007/s00216-011-5026-z. Epub 2011 May 5.
• [48] 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.
• [49] Adipogenic Effects and Gene Expression Profiling of Firemaster? 550 Components in Human Primary Preadipocytes. Environ Health Perspect. 2017 Sep 14;125(9):097013. doi: 10.1289/EHP1318.
• [50] Comparison of HepG2 and HepaRG by whole-genome gene expression analysis for the purpose of chemical hazard identification. Toxicol Sci. 2010 May;115(1):66-79.