General Information of Drug (ID: DMRHYAU)

Drug Name
MAZAPERTINE
Synonyms
Mazapertine; UNII-N0X1XW704P; CHEMBL10085; N0X1XW704P; 134208-17-6; RWJ-377796; Mazapertine [INN]; AC1L1TZN; AC1Q5K4U; SCHEMBL636631; DTXSID40158594; ZKZFPRUSWCYSGT-UHFFFAOYSA-N; BDBM50029257; L001470; Piperidino[3-[[4-(2-isopropoxyphenyl)piperazino]methyl]phenyl] ketone; 1-[3-[[4-[2-(1-methylethoxy)phenyl]-1-piperazinyl]methyl]benzoyl]piperidine; {3-[4-(2-Isopropoxy-phenyl)-piperazin-1-ylmethyl]-phenyl}-piperidin-1-yl-methanone; piperidin-1-yl-[3-[[4-(2-propan-2-yloxyphenyl)piperazin-1-yl]methyl]phenyl]methanone
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 421.6
Topological Polar Surface Area (xlogp) 4.4
Rotatable Bond Count (rotbonds) 6
Hydrogen Bond Donor Count (hbonddonor) 0
Hydrogen Bond Acceptor Count (hbondacc) 4
Chemical Identifiers
Formula
C26H35N3O2
IUPAC Name
piperidin-1-yl-[3-[[4-(2-propan-2-yloxyphenyl)piperazin-1-yl]methyl]phenyl]methanone
Canonical SMILES
CC(C)OC1=CC=CC=C1N2CCN(CC2)CC3=CC(=CC=C3)C(=O)N4CCCCC4
InChI
InChI=1S/C26H35N3O2/c1-21(2)31-25-12-5-4-11-24(25)28-17-15-27(16-18-28)20-22-9-8-10-23(19-22)26(30)29-13-6-3-7-14-29/h4-5,8-12,19,21H,3,6-7,13-18,20H2,1-2H3
InChIKey
ZKZFPRUSWCYSGT-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
60820
CAS Number
134208-17-6
TTD ID
D01WJZ

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 [1]
Adrenergic receptor alpha-1A (ADRA1A) TTNGILX ADA1A_HUMAN Inhibitor [1]
Adrenergic receptor alpha-1B (ADRA1B) TTBRKXS ADA1B_HUMAN Inhibitor [1]
Adrenergic receptor alpha-1D (ADRA1D) TT34BHT ADA1D_HUMAN Inhibitor [1]
Adrenergic receptor alpha-2A (ADRA2A) TTWG9A4 ADA2A_HUMAN Inhibitor [1]
Adrenergic receptor alpha-2B (ADRA2B) TTWM4TY ADA2B_HUMAN Inhibitor [1]
Adrenergic receptor alpha-2C (ADRA2C) TT2NUT5 ADA2C_HUMAN Inhibitor [1]
Dopamine D2 receptor (D2R) TTEX248 DRD2_HUMAN Inhibitor [1]
Dopamine D3 receptor (D3R) TT4C8EA DRD3_HUMAN Inhibitor [1]
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
Dopamine D3 receptor (D3R) DTT DRD3 5.74E-02 0.05 0.34
Dopamine D3 receptor (D3R) DTT DRD3 2.15E-01 -0.05 -0.46
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 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.
2 Synthesis and pharmacologic evaluation of 2-endo-amino-3-exo-isopropylbicyclo[2.2.1]heptane: a potent imidazoline1 receptor specific agent. J Med Chem. 1996 Mar 15;39(6):1193-5.
3 Effect of dihydroergocristine on blood pressure and activity at peripheral alpha-adrenoceptors in pithed rats. Eur J Pharmacol. 1984 Jan 13;97(1-2):21-7.
4 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: 520).
5 Effects of amosulalol, a combined alpha 1- and beta-adrenoceptor-blocking agent, on ischemic myocardial energy metabolism in dogs. J Pharm Sci. 1993 Mar;82(3):291-5.
6 Pharmacology of amezinium, a novel antihypotensive drug. III. Studies on the mechanism of action. Arzneimittelforschung. 1981;31(9a):1558-65.
7 Airway compromise and delayed death following attempted central vein injection of propylhexedrine. J Emerg Med. 1994 Nov-Dec;12(6):795-7.
8 Prolonged cardiovascular effects after unintentional ingestion of tetrahydrozoline. Clin Toxicol (Phila). 2008 Feb;46(2):171-2.
9 Rilmenidine-induced ocular hypotension: role of imidazoline1 and alpha 2 receptors. Curr Eye Res. 1996 Sep;15(9):943-50.
10 Alpha-adrenoceptor agonistic activity of oxymetazoline and xylometazoline. Fundam Clin Pharmacol. 2010 Dec;24(6):729-39.
11 Clinical pipeline report, company report or official report of Tonix Pharmaceuticals.
12 Radium 223 dichloride for prostate cancer treatment. Drug Des Devel Ther. 2017 Sep 6;11:2643-2651.
13 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
14 Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031127)
15 Pharmacology of pramipexole, a dopamine D3-preferring agonist useful in treating Parkinson's disease. Clin Neuropharmacol. 1998 May-Jun;21(3):141-51.
16 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
17 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
18 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.
19 Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
20 2018 FDA drug approvals.Nat Rev Drug Discov. 2019 Feb;18(2):85-89.
21 alpha2A-adrenergic receptors heterosynaptically regulate glutamatergic transmission in the bed nucleus of the stria terminalis. Neuroscience. 2009 Sep 29;163(1):339-51.
22 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.
23 Female Sexual Dysfunction: Therapeutic Options and Experimental Challenges. Cardiovasc Hematol Agents Med Chem. 2009 October; 7(4): 260-269.
24 Design and synthesis of novel dihydropyridine alpha-1a antagonists. Bioorg Med Chem Lett. 1999 Oct 4;9(19):2843-8.
25 Discovery of a new series of centrally active tricyclic isoxazoles combining serotonin (5-HT) reuptake inhibition with alpha2-adrenoceptor blocking... J Med Chem. 2005 Mar 24;48(6):2054-71.
26 alpha 2 adrenoceptors: classification, localization, mechanisms, and targets for drugs. J Med Chem. 1982 Dec;25(12):1389-401.
27 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.
28 Mirtazapine treatment after conditioning with methamphetamine alters subsequent expression of place preference. Drug Alcohol Depend. 2009 Jan 1;99(1-3):231-9.
29 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.
30 Activation of alpha1-adrenoceptors inhibits growth hormone secretion in humans. Exp Clin Endocrinol Diabetes. 2009 Oct;117(9):460-2.
31 Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34.
32 3-Benzisothiazolylpiperazine derivatives as potential atypical antipsychotic agents. J Med Chem. 1996 Jan 5;39(1):143-8.
33 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.
34 Drug repositioning: identifying and developing new uses for existing drugs. Nat Rev Drug Discov. 2004 Aug;3(8):673-83.
35 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.
36 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.
37 Current and novel approaches to the drug treatment of schizophrenia. J Med Chem. 2001 Feb 15;44(4):477-501.
38 Hughes B: 2009 FDA drug approvals. Nat Rev Drug Discov. 2010 Feb;9(2):89-92.
39 Mullard A: 2010 FDA drug approvals. Nat Rev Drug Discov. 2011 Feb;10(2):82-5.
40 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.
41 Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
42 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.
43 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.
44 Clinical pipeline report, company report or official report of Lundbeck.
45 Emerging drugs in neuropathic pain. Expert Opin Emerg Drugs. 2007 Mar;12(1):113-26.
46 Synthetic studies and pharmacological evaluations on the MDMA ('Ecstasy') antagonist nantenine. Bioorg Med Chem Lett. 2010 Jan 15;20(2):628-31.
47 Tricyclic isoxazolines: identification of R226161 as a potential new antidepressant that combines potent serotonin reuptake inhibition and alpha2-a... Bioorg Med Chem. 2007 Jun 1;15(11):3649-60.
48 The role of combination medical therapy in benign prostatic hyperplasia. Int J Impot Res. 2008 Dec;20 Suppl 3:S33-43.
49 Mechanisms of modafinil: A review of current research. Neuropsychiatr Dis Treat. 2007 June; 3(3): 349-364.
50 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.
51 Pharmacokinetics of moxisylyte in healthy volunteers after intracavernous injection of increasing doses. Eur J Clin Pharmacol. 1996;49(5):411-5.
52 Induction of prostate apoptosis by alpha1-adrenoceptor antagonists: mechanistic significance of the quinazoline component. Prostate Cancer Prostatic Dis. 2002;5(2):88-95.
53 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.
54 The hypotensive effect of trimazosin is not caused solely by alpha 1-adrenoceptor blockade. J Cardiovasc Pharmacol. 1984 Jan-Feb;6(1):142-50.
55 Antihypertensive action and blockade of alpha1-adrenoceptors by DL-017, a quinazoline derivative. J Cardiovasc Pharmacol. 2001 Dec;38(6):893-9.
56 5-HT1A receptor ligands and their therapeutic applications: review of new patents.Expert Opin Ther Pat. 2018 Sep;28(9):679-689.
57 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.
58 Dopaminergic synapses in the matrix of the ventrolateral striatum after chronic haloperidol treatment. Synapse. 2002 Aug;45(2):78-85.
59 CYP2D6 and DRD2 genes differentially impact pharmacodynamic sensitivity and time course of prolactin response to perphenazine. Pharmacogenet Genomics. 2007 Nov;17(11):989-93.
60 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.
61 Screening of domperidone in wastewater by high performance liquid chromatography and solid phase extraction methods. Talanta. 2006 Jan 15;68(3):928-31.
62 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).
63 Receptor reserve-dependent properties of antipsychotics at human dopamine D2 receptors. Eur J Pharmacol. 2009 Apr 1;607(1-3):35-40.
64 [The benzamides tiapride, sulpiride, and amisulpride in treatment for Tourette's syndrome]. Nervenarzt. 2007 Mar;78(3):264, 266-8, 270-1.
65 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.
66 Interactions between corticotropin-releasing hormone and serotonin: implications for the aetiology and treatment of anxiety disorders. Handb Exp Pharmacol. 2005;(169):181-204.
67 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.
68 2011 FDA drug approvals. Nat Rev Drug Discov. 2012 Feb 1;11(2):91-4.
69 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).
70 Urapidil. A reappraisal of its use in the management of hypertension. Drugs. 1998 Nov;56(5):929-55.
71 Clinical pipeline report, company report or official report of Jazz Pharmaceuticals.
72 Pharmacophore identification of alpha(1A)-adrenoceptor antagonists. Bioorg Med Chem Lett. 2005 Feb 1;15(3):657-64.
73 Pharma & Vaccines. Product Development Pipeline. April 29 2009.
74 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.