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

General Information of Drug (ID: DM3M4RA)

• Drug Name: 1-(2-Methoxy-phenyl)-piperazine Drug Info
• Synonyms: 1-(2-Methoxyphenyl)piperazine; 35386-24-4; 1-(o-Methoxyphenyl)piperazine; 1-(2-Methoxyphenyl)-piperazine; 2-MPP; UNII-81NJO1330A; N-(2-methoxyphenyl)piperazine; 1-(2-methoxy phenyl) piperazine; Piperazine, 1-(2-methoxyphenyl)-; 2-methoxyphenylpiperazine; 1-(2-METHOXYPHENYL) PIPERAZINE; CHEMBL9666; VNZLQLYBRIOLFZ-UHFFFAOYSA-N; 81NJO1330A; MFCD00005958; 1-(2-methoxyphenyl)piperazinehydrochloride; 2-methoxy-1-piperazinylbenzene; 1-(2-Methoxyphenyl)piperazine, 98+%; 1-(2-methoxyphenyl)piperazin

Indication

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

• Cross-matching ID:
  PubChem CID: 1346
  ChEBI ID: CHEBI:104020
  CAS Number: CAS 35386-24-4
  TTD Drug ID: DM3M4RA

Molecule-Related Drug Atlas

Drug(s) Targeting 5-HT 1D receptor (HTR1D)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Metergolin	DMJFP6G	Hyperprolactinaemia	5A60.1	Approved	[7]
Eletriptan	DMW649X	Migraine	8A80	Approved	[8]
Zolmitriptan	DM1IB4Q	Migraine	8A80	Approved	[8]
Frovatriptan	DM7RE8P	Migraine	8A80	Approved	[8]
Sumatriptan	DMVYXR8	Cluster headache	8A81.0	Approved	[9]
Rizatriptan	DMDJMA3	Migraine	8A80	Approved	[10]
Almogran	DM7I64Z	Migraine	8A80	Approved	[11]
Neu-P11	DMIQDFW	Alzheimer disease	8A20	Phase 2	[12]
FKB01MD	DM2O7NM	N. A.	N. A.	Phase 2	[13]
NXN-188	DMMBAIH	Migraine	8A80	Phase 2	[14]

Drug(s) Targeting 5-HT 6 receptor (HTR6)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
LU AE58054	DMWGRQD	Schizophrenia	6A20	Phase 3	[15]
SB-742457	DM6L4ZT	Alzheimer disease	8A20	Phase 3	[16]
AVN 211	DMVB4OS	Schizophrenia	6A20	Phase 2/3	[17]
SYN120	DMDF7XB	Parkinson disease	8A00.0	Phase 2	[18]
AVN 101	DMJFLBC	Alzheimer disease	8A20	Phase 2	[17]
SYN-120	DMPW0UL	Alzheimer disease	8A20	Phase 2	[19]
PF-05212377	DMPVQYR	Alzheimer disease	8A20	Phase 2	[20]
AVN 322	DMK2LGM	Cognitive impairment	6D71	Phase 2	[16]
SAM-531	DMHVJZ6	Alzheimer disease	8A20	Phase 2	[21]
SUVN-502	DMQD753	Alzheimer disease	8A20	Phase 2	[22]

Drug(s) Targeting 5-HT 2A receptor (HTR2A)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Metergolin	DMJFP6G	Hyperprolactinaemia	5A60.1	Approved	[23]
ZOTEPINE	DMF3VXA	Anxiety disorder	6B00-6B0Z	Approved	[24]
Iloperidone	DM6AUFY	Schizophrenia	6A20	Approved	[25]
Flibanserin	DM70DTN	Depression	6A70-6A7Z	Approved	[26]
Lurasidone hydrochloride	DMCVPXO	Schizophrenia	6A20	Approved	[27]
Aniracetam	DMOIFW0	Cerebrovascular ischaemia	8B1Z	Approved	[28]
lumateperone tosylate	DMQ8HOJ	Schizophrenia	6A20	Approved	[29]
Sarpogrelate	DMGLP6S	Diabetic complication	5A2Y	Approved	[30]
Pimavanserin	DMR7IVC	Parkinson disease	8A00.0	Approved	[31]
Zicronapine	DMP8ESD	Schizophrenia	6A20	Phase 3	[32]

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	[33]
Armodafinil	DMGB035	Malignant glioma	2A00.0	Approved	[34]
Alfuzosin	DMZVMKF	Benign prostatic hyperplasia	GA90	Approved	[35]
Moxisylyte	DMFCLYW	Erectile dysfunction	HA01.1	Approved	[36]
Terazosin	DM3JCVS	Benign prostatic hyperplasia	GA90	Approved	[37]
Bunazosin	DM4I8O7	Glaucoma/ocular hypertension	9C61	Approved	[38]
Trimazosin	DM1QLST	Congestive heart failure	BD10	Approved	[39]
MEDETOMIDINE	DMX9Y7V	Pain	MG30-MG3Z	Phase 2	[40]
DL-017	DMM8GZT	Hypertension	BA00-BA04	Phase 1	[41]
PMID30124346-Compound-LDT8	DM5MUNG	Benign prostatic hyperplasia	GA90	Patented	[42]

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Trazodone	DMK1GBJ	Depression	6A70-6A7Z	Approved	[8]
Buspirone	DMBS632	Anxiety disorder	6B00-6B0Z	Approved	[43]
OPC-34712	DMHG57U	Major depressive disorder	6A70.3	Approved	[44]
Vilazodone	DM4LECQ	Major depressive disorder	6A70.3	Approved	[45]
Flibanserin	DM70DTN	Depression	6A70-6A7Z	Approved	[26]
Gepirone	DMGX5Q0	Major depressive disorder	6A70.3	Approved	[46]
TERTATOLOL	DM2L3D5	Hypertension	BA00-BA04	Approved	[47]
Urapidil	DMD59GI	Hypertension	BA00-BA04	Approved	[48]
Treximet	DMU54QB	Migraine	8A80	Approved	[49]
CM-2395	DMASPWR	Schizophrenia	6A20	Phase 3	[50]

Drug(s) Targeting 5-HT 7 receptor (HTR7)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
RP5063	DMKUE8O	Schizophrenia	6A20	Phase 2	[13]
JNJ-18038683	DMV1T59	Major depressive disorder	6A70.3	Phase 2	[51]
AVN-101	DMOGFNI	Cognitive impairment	6D71	Phase 2	[52]
ATI-9242	DM6GKMU	Schizophrenia	6A20	Phase 1	[53]
PMID30124346-Compound-34TABLE4	DM2G3VE	Attention deficit hyperactivity disorder	6A05.Z	Patented	[42]
PMID30124346-Compound-13TABLE4	DMHTJVA	Attention deficit hyperactivity disorder	6A05.Z	Patented	[42]
Carbamide derivative 2	DMW5GI3	N. A.	N. A.	Patented	[54]
4-oxadiazole derivative 1	DMWFHKR	N. A.	N. A.	Patented	[54]
SB-269970	DM8WTGA	Sleep-wake disorder	7A00-7B2Z	Terminated	[55]
4-(4-butylpiperidin-1-yl)-1-o-tolylbutan-1-one	DMM9X0G	Discovery agent	N.A.	Investigative	[56]

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	[57]
NAFTOPIDIL	DMQ8R4E	Hypertension	BA00-BA04	Approved	[57]
Tamsulosin	DM5QF9V	Benign prostatic hyperplasia	GA90	Approved	[8]
Xatral	DMLHOA0	Benign prostatic hyperplasia	GA90	Approved	[58]
Dutasteride + tamsulosin	DM6P8HU	Benign prostatic hyperplasia	GA90	Phase 3	[49]
Besipirdine	DMLVNTA	Cognitive impairment	6D71	Phase 3	[59]
MEDETOMIDINE	DMX9Y7V	Pain	MG30-MG3Z	Phase 2	[40]
PMID30124346-Compound-LDT8	DM5MUNG	Benign prostatic hyperplasia	GA90	Patented	[42]
PMID30124346-Compound-LDT66	DMJMTNL	Benign prostatic hyperplasia	GA90	Patented	[42]
TIOSPIRONE	DME5QDP	N. A.	N. A.	Discontinued in Phase 3	[60]

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	[2]
5-HT 1D receptor (HTR1D)	TT6MSOK	5HT1D_HUMAN	Inhibitor	[3]
5-HT 2A receptor (HTR2A)	TTJQOD7	5HT2A_HUMAN	Inhibitor	[4]
5-HT 6 receptor (HTR6)	TTJS8PY	5HT6R_HUMAN	Inhibitor	[5]
5-HT 7 receptor (HTR7)	TTO9X1H	5HT7R_HUMAN	Agonist	[6]
Adrenergic receptor alpha-1A (ADRA1A)	TTNGILX	ADA1A_HUMAN	Inhibitor	[2]
Adrenergic receptor alpha-1D (ADRA1D)	TT34BHT	ADA1D_HUMAN	Inhibitor	[2]

References

• [1] 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: 280).
• [2] Pyrimido[5,4-b]indole derivatives. 1. A new class of potent and selective alpha 1 adrenoceptor ligands. J Med Chem. 1991 Jun;34(6):1850-4.
• [3] Activity of aromatic substituted phenylpiperazines lacking affinity for dopamine binding sites in a preclinical test of antipsychotic efficacy. J Med Chem. 1989 May;32(5):1052-6.
• [4] Synthesis and evaluation of phenyl- and benzoylpiperazines as potential serotonergic agents. J Med Chem. 1986 May;29(5):630-4.
• [5] 1-(1-Naphthyl)piperazine as a novel template for 5-HT6 serotonin receptor ligands. Bioorg Med Chem Lett. 2005 Mar 15;15(6):1707-11.
• [6] Molecular cloning and expression of a 5-hydroxytryptamine7 serotonin receptor subtype. J Biol Chem. 1993 Aug 25;268(24):18200-4.
• [7] Primary structure and functional characterization of a human 5-HT1D-type serotonin receptor. Mol Pharmacol. 1991 Aug;40(2):143-8.
• [8] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [9] Irritable bowel syndrome: new agents targeting serotonin receptor subtypes. Drugs. 2001;61(3):317-32.
• [10] An introduction to migraine: from ancient treatment to functional pharmacology and antimigraine therapy. Proc West Pharmacol Soc. 2002;45:199-210.
• [11] Efficacy and tolerability of subcutaneous almotriptan for the treatment of acute migraine: a randomized, double-blind, parallel-group, dose-finding study. Clin Ther. 2001 Nov;23(11):1867-75.
• [12] Clinical pipeline report, company report or official report of Neurim Pharmaceuticals.
• [13] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [14] Company report (NeurAxon)
• [15] Lu AE58054, a 5-HT6 antagonist, reverses cognitive impairment induced by subchronic phencyclidine in a novel object recognition test in rats. Int J Neuropsychopharmacol. 2010 Sep;13(8):1021-33.
• [16] 5-HT6 receptors and Alzheimer's disease. Alzheimers Res Ther. 2013; 5(2): 15.
• [17] Latrepirdine, a potential novel treatment for Alzheimer's disease and Huntington's chorea. Curr Opin Investig Drugs. 2010 January; 11(1): 80-91.
• [18] Therapeutic strategies for Parkinson disease: beyond dopaminergic drugs. Nat Rev Drug Discov. 2018 Nov;17(11):804-822.
• [19] The Serotonin-6 Receptor as a Novel Therapeutic Target. Exp Neurobiol. 2011 December; 20(4): 159-168.
• [20] PF-05212377 Alzheimer's Disease (Phase 2). Pfizer.
• [21] Activation of 5-HT6 receptors modulates sleep-wake activity and hippocampal theta oscillation. ACS Chem Neurosci. 2013 Jan 16;4(1):191-9.
• [22] Novel and Potent 5-Piperazinyl Methyl-N1-aryl Sulfonyl Indole Derivatives as 5-HT6 Receptor Ligands. ACS Med Chem Lett. 2010 October 14; 1(7): 340-344.
• [23] Pharmacological characterisation of the agonist radioligand binding site of 5-HT(2A), 5-HT(2B) and 5-HT(2C) receptors. Naunyn Schmiedebergs Arch Pharmacol. 2004 Aug;370(2):114-23.
• [24] Current and novel approaches to the drug treatment of schizophrenia. J Med Chem. 2001 Feb 15;44(4):477-501.
• [25] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [26] Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
• [27] Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
• [28] Anxiolytic effects of aniracetam in three different mouse models of anxiety and the underlying mechanism. Eur J Pharmacol. 2001 May 18;420(1):33-43.
• [29] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [30] Beneficial effects of sarpogrelate hydrochloride, a 5-HT2A receptor antagonist, supplemented with pioglitazone on diabetic model mice. Endocr Res. 2009;34(1-2):18-30.
• [31] Pimavanserin, a selective serotonin (5-HT)2A-inverse agonist, enhances the efficacy and safety of risperidone, 2mg/day, but does not enhance efficacy of haloperidol, 2mg/day: comparison with reference dose risperidone, 6mg/day.Schizophr Res.2012 Nov;141(2-3):144-52.
• [32] Clinical pipeline report, company report or official report of Lundbeck.
• [33] The role of combination medical therapy in benign prostatic hyperplasia. Int J Impot Res. 2008 Dec;20 Suppl 3:S33-43.
• [34] Mechanisms of modafinil: A review of current research. Neuropsychiatr Dis Treat. 2007 June; 3(3): 349-364.
• [35] 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.
• [36] Pharmacokinetics of moxisylyte in healthy volunteers after intracavernous injection of increasing doses. Eur J Clin Pharmacol. 1996;49(5):411-5.
• [37] Induction of prostate apoptosis by alpha1-adrenoceptor antagonists: mechanistic significance of the quinazoline component. Prostate Cancer Prostatic Dis. 2002;5(2):88-95.
• [38] 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.
• [39] The hypotensive effect of trimazosin is not caused solely by alpha 1-adrenoceptor blockade. J Cardiovasc Pharmacol. 1984 Jan-Feb;6(1):142-50.
• [40] 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.
• [41] Antihypertensive action and blockade of alpha1-adrenoceptors by DL-017, a quinazoline derivative. J Cardiovasc Pharmacol. 2001 Dec;38(6):893-9.
• [42] 5-HT1A receptor ligands and their therapeutic applications: review of new patents.Expert Opin Ther Pat. 2018 Sep;28(9):679-689.
• [43] Interactions between corticotropin-releasing hormone and serotonin: implications for the aetiology and treatment of anxiety disorders. Handb Exp Pharmacol. 2005;(169):181-204.
• [44] 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.
• [45] 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
• [46] Novel drugs and therapeutic targets for severe mood disorders. Neuropsychopharmacology. 2008 Aug;33(9):2080-92.
• [47] 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).
• [48] Urapidil. A reappraisal of its use in the management of hypertension. Drugs. 1998 Nov;56(5):929-55.
• [49] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [50] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031127)
• [51] Selective pharmacological blockade of the 5-HT7 receptor attenuates light and 8-OH-DPAT induced phase shifts of mouse circadian wheel running activity. Front Behav Neurosci. 2015 Jan 15;8:453.
• [52] AVN-101: A Multi-Target Drug Candidate for the Treatment of CNS Disorders. J Alzheimers Dis. 2016 May 25;53(2):583-620.
• [53] Pharmacological characteristics of ATI-9242, a Novel Atypical Antipsychotic. FASEB J, April, 2010, 24(Meeting Abstract Supplement),773.12.
• [54] Acyltransferase inhibitors: a patent review (2010-present).Expert Opin Ther Pat. 2015 Feb;25(2):145-58.
• [55] [(3)H]-SB-269970--A selective antagonist radioligand for 5-HT(7) receptors. Br J Pharmacol. 2000 May;130(2):409-17.
• [56] Discovery of N-{1-[3-(3-oxo-2,3-dihydrobenzo[1,4]oxazin-4-yl)propyl]piperidin-4-yl}-2-phenylacetamide (Lu AE51090): an allosteric muscarinic M1 rec... J Med Chem. 2010 Sep 9;53(17):6386-97.
• [57] Pharmacophore identification of alpha(1A)-adrenoceptor antagonists. Bioorg Med Chem Lett. 2005 Feb 1;15(3):657-64.
• [58] Pharma & Vaccines. Product Development Pipeline. April 29 2009.
• [59] 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.
• [60] 3-Benzisothiazolylpiperazine derivatives as potential atypical antipsychotic agents. J Med Chem. 1996 Jan 5;39(1):143-8.