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

General Information of Drug (ID: DM5176Y)

• Drug Name: [3H]N-methylspiperone Drug Info
• Synonyms: 3-N-Methylspiperone; N-Methylspiperone; N-Methylspiroperidol; 87539-19-3; UNII-5U54JM2T8G; 5U54JM2T8G; CHEMBL267932; 8-[4-(4-fluorophenyl)-4-oxobutyl]-3-methyl-1-phenyl-1,3,8-triazaspiro[45]decan-4-one; 8-(4-(4-Fluorophenyl)-4-oxobutyl)-3-methyl-1-phenyl-1,3,8-triazaspiro(45)decan-4-one; 1,3,8-Triazaspiro(45)decan-4-one, 8-(4-(4-fluorophenyl)-4-oxobutyl)-3-methyl-1-phenyl-; C24H28FN3O2; [3H]methylspiperone; Mespiperone; [3H]methylspiperone; N-METHYLSPIPERONE

Indication

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

• Cross-matching ID:
  PubChem CID: 119146
  CAS Number: CAS 87539-19-3
  TTD Drug ID: DM5176Y

Molecule-Related Drug Atlas

Drug(s) Targeting Dopamine D4 receptor (D4R)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Clozapine	DMFC71L	Schizophrenia	6A20	Approved	[4]
Phenyltoloxamine	DMKAEQW	Allergy	4A80-4A85	Approved	[5]
CM-2395	DMASPWR	Schizophrenia	6A20	Phase 3	[6]
RP5063	DMKUE8O	Schizophrenia	6A20	Phase 2	[7]
L-745,870	DMTGR25	Psychotic disorder	6A20-6A25	Phase 2	[8]
NGD 94-1	DMM1Y8F	Schizophrenia	6A20	Phase 1	[9]
ABT-724	DMDQVY4	Erectile dysfunction	HA01.1	Discontinued in Phase 2	[10]
Lu-35138	DMQ7A35	Psychotic disorder	6A20-6A25	Discontinued in Phase 2	[11]
NGD-94-4	DMZ9WLO	Schizophrenia	6A20	Discontinued in Phase 1	[12]
PD-165167	DMD0GB4	Schizophrenia	6A20	Preclinical	[9]

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 Dopamine D2 receptor (D2R)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Dopamine	DMPGUCF	Acromegaly	5A60.0	Approved	[23]
Haloperidol	DM96SE0	Delirium		Approved	[24]
Perphenazine	DMA4MRX	Schizophrenia	6A20	Approved	[25]
Perazine	DM2AOTZ	Psychotic disorder	6A20-6A25	Approved	[26]
Domperidone	DMBDPY0	Gastrointestinal disease	DE2Z	Approved	[27]
Levodopa	DMN3E57	Parkinson disease	8A00.0	Approved	[28]
Quetiapine	DM1N62C	Anorexia nervosa cachexia	6B80	Approved	[29]
Pimozide	DMW83TP	Schizophrenia	6A20	Approved	[30]
Chlorpromazine	DMBGZI3	Acute intermittent hepatic porphyria	5C58.11	Approved	[31]
Iloperidone	DM6AUFY	Schizophrenia	6A20	Approved	[15]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
5-HT 2A receptor (HTR2A)	TTJQOD7	5HT2A_HUMAN	Antagonist	[2]
Dopamine D2 receptor (D2R)	TTEX248	DRD2_HUMAN	Antagonist	[3]
Dopamine D4 receptor (D4R)	TTE0A2F	DRD4_HUMAN	Antagonist	[3]

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: 196).
• [2] Differential modes of agonist binding to 5-hydroxytryptamine(2A) serotonin receptors revealed by mutation and molecular modeling of conserved residues in transmembrane region 5. Mol Pharmacol. 2000 Nov;58(5):877-86.
• [3] Nonconserved residues in the second transmembrane-spanning domain of the D(4) dopamine receptor are molecular determinants of D(4)-selective pharmacology. Mol Pharmacol. 2000 Jan;57(1):144-52.
• [4] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health & Human Services.
• [5] Dopamine/serotonin receptor ligands. 9. Oxygen-containing midsized heterocyclic ring systems and nonrigidized analogues. A step toward dopamine D5 ... J Med Chem. 2004 Aug 12;47(17):4155-8.
• [6] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800031127)
• [7] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [8] Dopamine D4 receptor involvement in the discriminative stimulus effects in rats of LSD, but not the phenethylamine hallucinogen DOI. Psychopharmacology (Berl). 2009 Apr;203(2):265-77.
• [9] The pipeline and future of drug development in schizophrenia. Mol Psychiatry. 2007 Oct;12(10):904-22.
• [10] Activation of dopamine D4 receptors by ABT-724 induces penile erection in rats. Proc Natl Acad Sci U S A. 2004 April 27; 101(17): 6758-6763.
• [11] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800014237)
• [12] I. NGD 94-1: identification of a novel, high-affinity antagonist at the human dopamine D4 receptor. J Pharmacol Exp Ther. 1997 Aug;282(2):1011-9.
• [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 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.
• [24] Dopaminergic synapses in the matrix of the ventrolateral striatum after chronic haloperidol treatment. Synapse. 2002 Aug;45(2):78-85.
• [25] CYP2D6 and DRD2 genes differentially impact pharmacodynamic sensitivity and time course of prolactin response to perphenazine. Pharmacogenet Genomics. 2007 Nov;17(11):989-93.
• [26] 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.
• [27] Screening of domperidone in wastewater by high performance liquid chromatography and solid phase extraction methods. Talanta. 2006 Jan 15;68(3):928-31.
• [28] 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).
• [29] Receptor reserve-dependent properties of antipsychotics at human dopamine D2 receptors. Eur J Pharmacol. 2009 Apr 1;607(1-3):35-40.
• [30] [The benzamides tiapride, sulpiride, and amisulpride in treatment for Tourette's syndrome]. Nervenarzt. 2007 Mar;78(3):264, 266-8, 270-1.
• [31] 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.