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

General Information of Drug (ID: DME5QDP)

• Drug Name: TIOSPIRONE Drug Info
• Synonyms: TIOSPIRONE; tiaspirone; Tiospirone [INN]; Tiospironum [Latin]; Tiospirona [Spanish]; 87691-91-6; UNII-35C6UMO5SR; 35C6UMO5SR; CHEMBL35057; BMY-13859; Tiospironum; Tiospirona; 8-[4-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]butyl]-8-azaspiro[4.5]decane-7,9-dione; 8-Azaspiro(4,5)decane-7,9-dione, 8-(4-(4-(1,2-benzisothiazol-3-yl)-1-piperazinyl)butyl)-; BMY-13859-1; tiospyrone; TIOSPERONE; AC1L1JPQ; 8-(4-(4-(1,2-benzisothiazol-3-yl)-1-piperazinyl)butyl)-8-azaspiro(4.5)decane-7,9-dione hydrochloride; SCHEMBL78696; GTPL101
• Cross-matching ID:
  PubChem CID: 55752
  CAS Number: CAS 87691-91-6
  TTD Drug ID: DME5QDP

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	[3]
Propericiazine	DME9JNL	Psychiatric disorder	6E8Z	Approved	[4]
Methoxamine	DMF5XQH	Hypertension	BA00-BA04	Approved	[5]
Phendimetrazine	DM6TS1N	Obesity	5B81	Approved	[6]
MEDETOMIDINE	DMX9Y7V	Pain	MG30-MG3Z	Phase 2	[7]
Sunepitron	DM6M8ZX	N. A.	N. A.	Discontinued in Phase 3	[8]
MAZAPERTINE	DMRHYAU	N. A.	N. A.	Discontinued in Phase 2	[9]
SOU-001	DMPAEK5	Urinary incontinence	MF50.2	Discontinued in Phase 2	[10]
SNAP-5089	DMROJEN	Heart arrhythmia	BC65	Terminated	[11]
WB-4101	DMQU8B1	N. A.	N. A.	Terminated	[12]

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Metergolin	DMJFP6G	Hyperprolactinaemia	5A60.1	Approved	[13]
ZOTEPINE	DMF3VXA	Anxiety disorder	6B00-6B0Z	Approved	[14]
Iloperidone	DM6AUFY	Schizophrenia	6A20	Approved	[15]
Flibanserin	DM70DTN	Depression	6A70-6A7Z	Approved	[16]
Lurasidone hydrochloride	DMCVPXO	Schizophrenia	6A20	Approved	[17]
Aniracetam	DMOIFW0	Cerebrovascular ischaemia	8B1Z	Approved	[18]
lumateperone tosylate	DMQ8HOJ	Schizophrenia	6A20	Approved	[19]
Sarpogrelate	DMGLP6S	Diabetic complication	5A2Y	Approved	[20]
Pimavanserin	DMR7IVC	Parkinson disease	8A00.0	Approved	[21]
Zicronapine	DMP8ESD	Schizophrenia	6A20	Phase 3	[22]

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	[23]
Armodafinil	DMGB035	Malignant glioma	2A00.0	Approved	[24]
Alfuzosin	DMZVMKF	Benign prostatic hyperplasia	GA90	Approved	[25]
Moxisylyte	DMFCLYW	Erectile dysfunction	HA01.1	Approved	[26]
Terazosin	DM3JCVS	Benign prostatic hyperplasia	GA90	Approved	[27]
Bunazosin	DM4I8O7	Glaucoma/ocular hypertension	9C61	Approved	[28]
Trimazosin	DM1QLST	Congestive heart failure	BD10	Approved	[29]
MEDETOMIDINE	DMX9Y7V	Pain	MG30-MG3Z	Phase 2	[7]
DL-017	DMM8GZT	Hypertension	BA00-BA04	Phase 1	[30]
PMID30124346-Compound-LDT8	DM5MUNG	Benign prostatic hyperplasia	GA90	Patented	[31]

Drug(s) Targeting Dopamine D2 receptor (D2R)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dopamine	DMPGUCF	Acromegaly	5A60.0	Approved	[32]
Haloperidol	DM96SE0	Delirium		Approved	[33]
Perphenazine	DMA4MRX	Schizophrenia	6A20	Approved	[34]
Perazine	DM2AOTZ	Psychotic disorder	6A20-6A25	Approved	[35]
Domperidone	DMBDPY0	Gastrointestinal disease	DE2Z	Approved	[36]
Levodopa	DMN3E57	Parkinson disease	8A00.0	Approved	[37]
Quetiapine	DM1N62C	Anorexia nervosa cachexia	6B80	Approved	[38]
Pimozide	DMW83TP	Schizophrenia	6A20	Approved	[39]
Chlorpromazine	DMBGZI3	Acute intermittent hepatic porphyria	5C58.11	Approved	[40]
Iloperidone	DM6AUFY	Schizophrenia	6A20	Approved	[15]

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

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Trazodone	DMK1GBJ	Depression	6A70-6A7Z	Approved	[41]
Buspirone	DMBS632	Anxiety disorder	6B00-6B0Z	Approved	[42]
OPC-34712	DMHG57U	Major depressive disorder	6A70.3	Approved	[43]
Vilazodone	DM4LECQ	Major depressive disorder	6A70.3	Approved	[44]
Flibanserin	DM70DTN	Depression	6A70-6A7Z	Approved	[16]
Gepirone	DMGX5Q0	Major depressive disorder	6A70.3	Approved	[45]
TERTATOLOL	DM2L3D5	Hypertension	BA00-BA04	Approved	[46]
Urapidil	DMD59GI	Hypertension	BA00-BA04	Approved	[47]
Treximet	DMU54QB	Migraine	8A80	Approved	[48]
CM-2395	DMASPWR	Schizophrenia	6A20	Phase 3	[49]

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	[50]
NAFTOPIDIL	DMQ8R4E	Hypertension	BA00-BA04	Approved	[50]
Tamsulosin	DM5QF9V	Benign prostatic hyperplasia	GA90	Approved	[41]
Xatral	DMLHOA0	Benign prostatic hyperplasia	GA90	Approved	[51]
Dutasteride + tamsulosin	DM6P8HU	Benign prostatic hyperplasia	GA90	Phase 3	[48]
Besipirdine	DMLVNTA	Cognitive impairment	6D71	Phase 3	[52]
MEDETOMIDINE	DMX9Y7V	Pain	MG30-MG3Z	Phase 2	[7]
PMID30124346-Compound-LDT8	DM5MUNG	Benign prostatic hyperplasia	GA90	Patented	[31]
PMID30124346-Compound-LDT66	DMJMTNL	Benign prostatic hyperplasia	GA90	Patented	[31]
Sunepitron	DM6M8ZX	N. A.	N. A.	Discontinued in Phase 3	[8]

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]
5-HT 2A receptor (HTR2A)	TTJQOD7	5HT2A_HUMAN	Inhibitor	[2]
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]
Dopamine D2 receptor (D2R)	TTEX248	DRD2_HUMAN	Inhibitor	[2]

References

• [1] Synthesis and biological activity of the putative metabolites of the atypical antipsychotic agent tiospirone. J Med Chem. 1991 Nov;34(11):3316-28.
• [2] 3-Benzisothiazolylpiperazine derivatives as potential atypical antipsychotic agents. J Med Chem. 1996 Jan 5;39(1):143-8.
• [3] Mirtazapine treatment after conditioning with methamphetamine alters subsequent expression of place preference. Drug Alcohol Depend. 2009 Jan 1;99(1-3):231-9.
• [4] 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.
• [5] Activation of alpha1-adrenoceptors inhibits growth hormone secretion in humans. Exp Clin Endocrinol Diabetes. 2009 Oct;117(9):460-2.
• [6] Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34.
• [7] 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.
• [8] 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.
• [9] 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.
• [10] Drug repositioning: identifying and developing new uses for existing drugs. Nat Rev Drug Discov. 2004 Aug;3(8):673-83.
• [11] 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.
• [12] Alpha- and beta-adrenoceptors: from the gene to the clinic. 1. Molecular biology and adrenoceptor subclassification. J Med Chem. 1995 Sep 1;38(18):3415-44.
• [13] 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.
• [14] Current and novel approaches to the drug treatment of schizophrenia. J Med Chem. 2001 Feb 15;44(4):477-501.
• [15] Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
• [16] Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
• [17] Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
• [18] 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.
• [19] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [20] 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.
• [21] 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.
• [22] Clinical pipeline report, company report or official report of Lundbeck.
• [23] The role of combination medical therapy in benign prostatic hyperplasia. Int J Impot Res. 2008 Dec;20 Suppl 3:S33-43.
• [24] Mechanisms of modafinil: A review of current research. Neuropsychiatr Dis Treat. 2007 June; 3(3): 349-364.
• [25] 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.
• [26] Pharmacokinetics of moxisylyte in healthy volunteers after intracavernous injection of increasing doses. Eur J Clin Pharmacol. 1996;49(5):411-5.
• [27] Induction of prostate apoptosis by alpha1-adrenoceptor antagonists: mechanistic significance of the quinazoline component. Prostate Cancer Prostatic Dis. 2002;5(2):88-95.
• [28] 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.
• [29] The hypotensive effect of trimazosin is not caused solely by alpha 1-adrenoceptor blockade. J Cardiovasc Pharmacol. 1984 Jan-Feb;6(1):142-50.
• [30] Antihypertensive action and blockade of alpha1-adrenoceptors by DL-017, a quinazoline derivative. J Cardiovasc Pharmacol. 2001 Dec;38(6):893-9.
• [31] 5-HT1A receptor ligands and their therapeutic applications: review of new patents.Expert Opin Ther Pat. 2018 Sep;28(9):679-689.
• [32] 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.
• [33] Dopaminergic synapses in the matrix of the ventrolateral striatum after chronic haloperidol treatment. Synapse. 2002 Aug;45(2):78-85.
• [34] CYP2D6 and DRD2 genes differentially impact pharmacodynamic sensitivity and time course of prolactin response to perphenazine. Pharmacogenet Genomics. 2007 Nov;17(11):989-93.
• [35] 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.
• [36] Screening of domperidone in wastewater by high performance liquid chromatography and solid phase extraction methods. Talanta. 2006 Jan 15;68(3):928-31.
• [37] 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).
• [38] Receptor reserve-dependent properties of antipsychotics at human dopamine D2 receptors. Eur J Pharmacol. 2009 Apr 1;607(1-3):35-40.
• [39] [The benzamides tiapride, sulpiride, and amisulpride in treatment for Tourette's syndrome]. Nervenarzt. 2007 Mar;78(3):264, 266-8, 270-1.
• [40] 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.
• [41] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [42] Interactions between corticotropin-releasing hormone and serotonin: implications for the aetiology and treatment of anxiety disorders. Handb Exp Pharmacol. 2005;(169):181-204.
• [43] 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.
• [44] 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
• [45] Novel drugs and therapeutic targets for severe mood disorders. Neuropsychopharmacology. 2008 Aug;33(9):2080-92.
• [46] 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).
• [47] Urapidil. A reappraisal of its use in the management of hypertension. Drugs. 1998 Nov;56(5):929-55.
• [48] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [49] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031127)
• [50] Pharmacophore identification of alpha(1A)-adrenoceptor antagonists. Bioorg Med Chem Lett. 2005 Feb 1;15(3):657-64.
• [51] Pharma & Vaccines. Product Development Pipeline. April 29 2009.
• [52] 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.