General Information of Drug (ID: DME5QDP)

Drug Name
TIOSPIRONE
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
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 440.6
Topological Polar Surface Area (xlogp) 4.3
Rotatable Bond Count (rotbonds) 6
Hydrogen Bond Donor Count (hbonddonor) 0
Hydrogen Bond Acceptor Count (hbondacc) 6
Chemical Identifiers
Formula
C24H32N4O2S
IUPAC Name
8-[4-[4-(1,2-benzothiazol-3-yl)piperazin-1-yl]butyl]-8-azaspiro[4.5]decane-7,9-dione
Canonical SMILES
C1CCC2(C1)CC(=O)N(C(=O)C2)CCCCN3CCN(CC3)C4=NSC5=CC=CC=C54
InChI
InChI=1S/C24H32N4O2S/c29-21-17-24(9-3-4-10-24)18-22(30)28(21)12-6-5-11-26-13-15-27(16-14-26)23-19-7-1-2-8-20(19)31-25-23/h1-2,7-8H,3-6,9-18H2
InChIKey
ZFZPJDFBJFHYIV-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
55752
CAS Number
87691-91-6
TTD ID
D01RCS

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]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
5-HT 1A receptor (HTR1A) DTT HTR1A 7.49E-01 -0.02 -0.06
5-HT 1A receptor (HTR1A) DTT HTR1A 3.45E-01 -0.02 -0.14
5-HT 2A receptor (HTR2A) DTT HTR2A 1.68E-01 -0.3 -0.14
5-HT 2A receptor (HTR2A) DTT HTR2A 5.59E-01 0.15 0.21
Dopamine D2 receptor (D2R) DTT DRD2 9.39E-01 -0.01 -0.05
Dopamine D2 receptor (D2R) DTT DRD2 9.91E-01 -0.02 -0.28
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

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 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).
46 Urapidil. A reappraisal of its use in the management of hypertension. Drugs. 1998 Nov;56(5):929-55.
47 Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
48 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031127)
49 Clinical pipeline report, company report or official report of Jazz Pharmaceuticals.
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.