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

General Information of Drug (ID: DMWDCV1)

• Drug Name: N-[3H]alpha-methylhistamine Drug Info
• Synonyms: N-alpha-methylhistamine; 1H-Imidazole-4-ethanamine, N-methyl-; 4-(2-Methylaminoethyl)imidazole; N(sup alpha)-Methylhistamine; NAMH; Nalpha-Methylhistamine; UNII-Y7QR253130; N(alpha)-methylhistamine; Y7QR253130; Imidazole, 4-[2-(methylamino)ethyl]-; Imidazole, 4-(2-(methylamino)ethyl)-; [2-(1H-imidazol-5-yl)ethyl](methyl)amine; 2-(3H-imidazol-4-yl)-N-methylethanamine; [3H]-Na-methylhistamine; [3H]NAMH; N-alpha-methyl histamine

Indication

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

• Cross-matching ID:
  PubChem CID: 912
  CAS Number: CAS 673-50-7
  TTD Drug ID: DMWDCV1

Molecule-Related Drug Atlas

Drug(s) Targeting Histamine H4 receptor (H4R)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
PF-3893787	DMC2FAL	Atopic dermatitis	EA80	Phase 2	[5]
JNJ-38518168	DM9UMIO	Plaque psoriasis	EA90.0	Phase 2	[6]
UR-63325	DME6X27	Allergic rhinitis	CA08.0	Phase 2	[7]
Thioperamide	DM8S593	Cognitive impairment	6D71	Terminated	[8]
2-(2-(4-tert-Butylphenylthio)ethyl)-1H-imidazole	DMZVBPG	Discovery agent	N.A.	Investigative	[9]
impromidine	DMTDRPM	Discovery agent	N.A.	Investigative	[10]
burimamide	DMZ2VYG	Discovery agent	N.A.	Investigative	[11]
Imetit	DMMJ6NS	Discovery agent	N.A.	Investigative	[12]
[125I]iodophenpropit	DMN4ABU	Discovery agent	N.A.	Investigative	[13]
(R)-alpha-methylhistamine	DMKAW4P	Discovery agent	N.A.	Investigative	[14]

Drug(s) Targeting Histamine H3 receptor (H3R)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Pitolisant	DM8RFNJ	Excessive daytime sleepiness	MG42	Approved	[15]
SUVN-G3031	DM3BO8G	Cognitive impairment	6D71	Phase 3	[16]
JNJ-17216498	DM1GRCU	Narcolepsy	7A20	Phase 2	[17]
GSK239512	DMBJMZC	Alzheimer disease	8A20	Phase 2	[18]
JNJ-39220675	DM0WY3H	Alcohol dependence	6C40.2	Phase 2	[19]
AZD-5213	DMOZ04X	Alzheimer disease	8A20	Phase 2	[20]
Bavisant	DM6CVZ5	Attention deficit hyperactivity disorder	6A05.Z	Phase 2	[21]
ABT-288	DM7X54F	Alzheimer disease	8A20	Phase 2	[22]
SAR-110894	DMCLEXM	Alzheimer disease	8A20	Phase 2	[20]
ABT-652	DMLEO2Z	Diabetic neuropathy	8C0Z	Phase 2	[23]

Drug(s) Affected By Histamine H3 receptor (HRH3)

Drug Name	Drug ID	Indication	ICD 11	Highest Status	REF
Tretinoin	DM49DUI	Acne vulgaris	ED80	Approved	[24]
Valproate	DMCFE9I	Epilepsy	8A60-8A68	Approved	[25]
Irdabisant	DMR3E4L	Cognitive impairment	6D71	Phase 1	[26]
Benzo(a)pyrene	DMN7J43	N. A.	N. A.	Phase 1	[27]
Clobenpropit	DM537OH	Discovery agent	N.A.	Investigative	[28]
Trichostatin A	DM9C8NX	Solid tumour/cancer	2A00-2F9Z	Investigative	[29]
Guanosine-5'-Triphosphate	DMV2OJX	Discovery agent	N.A.	Investigative	[26]

Molecular Interaction Atlas of This Drug

Drug Therapeutic Target (DTT)

DTT Name	DTT ID	UniProt ID	MOA	REF
Histamine H3 receptor (H3R)	TT9JNIC	HRH3_HUMAN	Agonist	[2]
Histamine H4 receptor (H4R)	TTXJ178	HRH4_HUMAN	Agonist	[3]

Drug Off-Target (DOT)

DOT Name	DOT ID	UniProt ID	Interaction	REF
Histamine H3 receptor (HRH3)	OT7GF3AI	HRH3_HUMAN	Protein Interaction/Cellular Processes	[4]

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: 1239).
• [2] Molecular and pharmacological characterization of the mouse histamine H3 receptor. Eur J Pharmacol. 2003 Apr 25;467(1-3):57-65.
• [3] Histamine induces cytoskeletal changes in human eosinophils via the H(4) receptor. Br J Pharmacol. 2003 Nov;140(6):1117-27.
• [4] Discovery of two clinical histamine H(3) receptor antagonists: trans-N-ethyl-3-fluoro-3-[3-fluoro-4-(pyrrolidinylmethyl)phenyl]cyclobutanecarboxamide (PF-03654746) and trans-3-fluoro-3-[3-fluoro-4-(pyrrolidin-1-ylmethyl)phenyl]-N-(2-methylpropyl)cyclobutanecarboxamide (PF-03654764). J Med Chem. 2011 Nov 10;54(21):7602-20. doi: 10.1021/jm200939b. Epub 2011 Oct 7.
• [5] Challenges of drug discovery in novel target space. The discovery and evaluation of PF-3893787: a novel histamine H4 receptor antagonist. Bioorg Med Chem Lett. 2011 Nov 1;21(21):6596-602.
• [6] The histamine H4 receptor: from orphan to the clinic. Front Pharmacol. 2015; 6: 65.
• [7] Azines as histamine H4 receptor antagonists. Front Biosci (Schol Ed). 2012 Jan 1;4:967-87.
• [8] Role of histamine in short- and long-term effects of methamphetamine on the developing mouse brain. J Neurochem. 2008 Nov;107(4):976-86.
• [9] Synthesis and structure-activity relationships of N-aryl-piperidine derivatives as potent (partial) agonists for human histamine H3 receptor. Bioorg Med Chem. 2010 Jul 15;18(14):5441-8.
• [10] Evaluation of histamine H1-, H2-, and H3-receptor ligands at the human histamine H4 receptor: identification of 4-methylhistamine as the first pote... J Pharmacol Exp Ther. 2005 Sep;314(3):1310-21.
• [11] Comparison of human, mouse, rat, and guinea pig histamine H4 receptors reveals substantial pharmacological species variation. J Pharmacol Exp Ther. 2001 Oct;299(1):121-30.
• [12] Histamine excites neonatal rat sympathetic preganglionic neurons in vitro via activation of H1 receptors. J Neurophysiol. 2006 Apr;95(4):2492-500.
• [13] Discovery of novel human histamine H4 receptor ligands by large-scale structure-based virtual screening. J Med Chem. 2008 Jun 12;51(11):3145-53.
• [14] Cloning and pharmacological characterization of a fourth histamine receptor (H(4)) expressed in bone marrow. Mol Pharmacol. 2001 Mar;59(3):420-6.
• [15] Drugs@FDA. U.S. Food and Drug Administration. U.S. Department of Health Human Services. 2019
• [16] Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
• [17] Acute wake-promoting actions of JNJ-5207852, a novel, diamine-based H3 antagonist. Br J Pharmacol. 2004 Nov;143(5):649-61.
• [18] Clinical pipeline report, company report or official report of GlaxoSmithKline (2009).
• [19] JNJ-39220675, a novel selective histamine H3 receptor antagonist, reduces the abuse-related effects of alcohol in rats. Psychopharmacology (Berl). 2011 Apr;214(4):829-41.
• [20] SAR110894, a potent histamine H receptor antagonist, displays procognitive effects in rodents. Pharmacol Biochem Behav. 2012 Aug;102(2):203-14.
• [21] Randomized clinical study of a histamine H3 receptor antagonist for the treatment of adults with attention-deficit hyperactivity disorder. CNS Drugs. 2012 May 1;26(5):421-34.
• [22] A randomized study of H3 antagonist ABT-288 in mild-to-moderate Alzheimer's dementia.J Alzheimers Dis.2014;42(3):959-71.
• [23] Trusted, scientifically sound profiles of drug programs, clinical trials, safety reports, and company deals, written by scientists. Springer. 2015. Adis Insight (drug id 800032225)
• [24] Phenotypic characterization of retinoic acid differentiated SH-SY5Y cells by transcriptional profiling. PLoS One. 2013 May 28;8(5):e63862.
• [25] Integrative omics data analyses of repeated dose toxicity of valproic acid in vitro reveal new mechanisms of steatosis induction. Toxicology. 2018 Jan 15;393:160-170.
• [26] Discovery and characterization of 6-{4-[3-(R)-2-methylpyrrolidin-1-yl)propoxy]phenyl}-2H-pyridazin-3-one (CEP-26401, irdabisant): a potent, selective histamine H3 receptor inverse agonist. J Med Chem. 2011 Jul 14;54(13):4781-92. doi: 10.1021/jm200401v. Epub 2011 Jun 2.
• [27] Air pollution and DNA methylation alterations in lung cancer: A systematic and comparative study. Oncotarget. 2017 Jan 3;8(1):1369-1391. doi: 10.18632/oncotarget.13622.
• [28] Molecular determinants of ligand binding modes in the histamine H(4) receptor: linking ligand-based three-dimensional quantitative structure-activity relationship (3D-QSAR) models to in silico guided receptor mutagenesis studies. J Med Chem. 2011 Dec 8;54(23):8136-47. doi: 10.1021/jm201042n. Epub 2011 Nov 7.
• [29] A trichostatin A expression signature identified by TempO-Seq targeted whole transcriptome profiling. PLoS One. 2017 May 25;12(5):e0178302. doi: 10.1371/journal.pone.0178302. eCollection 2017.