Page last updated: 2024-11-06

4-methylhistamine

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Description

4-methylhistamine: RN given refers to parent cpd [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

4-methylhistamine : An aralkylamino compound that is histamine bearing a methyl substituent at the 5 position on the ring. [Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Cross-References

ID SourceID
PubMed CID37463
CHEMBL ID275443
CHEBI ID74760
SCHEMBL ID606803
SCHEMBL ID11452941
MeSH IDM0085062

Synonyms (44)

Synonym
gtpl1269
5-methylhistamine
4-methylhistamine
1h-imidazo-4-ethanamine, 5-methyl-
imidazole, 4-(2-aminoethyl)-5-methyl-
5(4)-methylhistamine
1h-imidazole-4-ethanamine, 5-methyl-
methylhistamine-4
2-(5-methyl-1h-imidazol-4-yl)ethan-1-amine
bdbm22880
PDSP1_000400
PDSP2_000398
2-(5-methyl-1h-imidazol-4-yl)ethanamine
L000072
CHEMBL275443
chebi:74760 ,
C17929
36507-31-0
AKOS012036768
54st71p9ee ,
unii-54st71p9ee
BRD-K70821460-300-01-6
5-(2-aminoethyl)-4-methylimidazole
1h-imidazole-5-ethanamine, 4-methyl-
2-(5-methyl-4-imidazolyl)ethylamine
4-(2-aminoethyl)-5-methylimidazole
SCHEMBL606803
AKOS022477289
2-(5-methyl-3h-imidazol-4-yl)-ethylamine
AB45417
SCHEMBL11452941
UGYXPZQILZRKJJ-UHFFFAOYSA-N
2-(5-methyl-1h-imidazol-4-yl)ethylamine #
5-methyl-1h-imidazole-4-ethanamine
p-methylhistamine
2-(4-methyl-1h-imidazol-5-yl)ethanamine
FT-0736440
Q4637182
VS-0251
HMS3742E13
DTXSID90957812
EN300-82322
CS-0626812
HY-W580721

Research Excerpts

Dosage Studied

ExcerptRelevanceReference
" H1-agonists (2-methylHi and 2-thiazolylethylamine) also depressed the avoidance response; their dose-response lines run parallel to that of Hi."( The effects of histamine and some related compounds on conditioned avoidance response in rats.
Akahori, H; Kamei, C; Kitazumi, K; Tasaka, K, 1985
)
0.27
" The H1-antagonist clemizole antagonized competitively the effect of histamine but the H2-antagonist ranitidine did not modify the dose-response curve to histamine in the guinea-pig colon."( Pharmacological investigation into the effects of histamine and histamine analogues on guinea-pig and rat colon in vitro.
Aguilar, MJ; Morales-Olivas, FJ; Rubio, E, 1986
)
0.27
" Pretreatment of parenchymal strips with cimetidine or YM-11170, H2-receptor antagonists, resulted in a parallel shift of the dimaprit dose-response curve to the right."( Effects of histamine H2-receptor agonists and antagonists on isolated guinea-pig airway muscles.
Tomioka, K; Yamada, T, 1982
)
0.26
" The present work investigates in vitro the inhibitory dose-response curves to histamine, 4-methyl-histamine and 2-pyridylethylamine in depolarized (KCl 37 mM) uterus from estrogenous sensitized rats."( [Inhibitory action of histamine on the isolated rat uterus].
Esplugues, J; Marti-Bonmati, E; Morales-Olivas, FJ; Morcillo, E; Rubio, E,
)
0.13
" To better histamine stimulation of pepsin, histamine was used at doses at the lower end of the dose-response scale in five dogs with gastric fistula."( Histamine H-2 receptor stimulation and inhibition of pepsin secretion in the dog.
Hirschowitz, BI; Molina, E; Rentz, J, 1981
)
0.26
" If the mice were dosed daily (i."( Effect of histamine agonists and antagonists on the production of murine reaginic antibodies.
Baker, AP; Chakrin, LW; Holden, DA; Smith, WJ; Sung, CP, 1981
)
0.26
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (2)

RoleDescription
metaboliteAny intermediate or product resulting from metabolism. The term 'metabolite' subsumes the classes commonly known as primary and secondary metabolites.
histamine agonistA drug that binds to and activates histamine receptors. Although they have been suggested for a variety of clinical applications, histamine agonists have so far been more widely used in research than therapeutically.
[role information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Drug Classes (2)

ClassDescription
imidazolesA five-membered organic heterocycle containing two nitrogen atoms at positions 1 and 3, or any of its derivatives; compounds containing an imidazole skeleton.
aralkylamino compoundAn organic amino compound in which an aminoalkyl group is linked to an arene.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Protein Targets (7)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Histamine H2 receptorHomo sapiens (human)Ki7.94330.00062.197310.0000AID548984
Histamine H4 receptorHomo sapiens (human)Ki0.05010.00060.478710.0000AID1798265; AID548981
Histamine H3 receptorHomo sapiens (human)Ki6.30960.00010.33998.5110AID548987
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Activation Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Histamine H2 receptorHomo sapiens (human)EC50 (µMol)3.02320.11481.77695.4954AID471096; AID548985
Histamine H1 receptorHomo sapiens (human)EC50 (µMol)15.84890.00040.18810.7943AID471095
Histamine H4 receptorRattus norvegicus (Norway rat)EC50 (µMol)2.51190.00261.06683.7153AID548999
Histamine H4 receptorMus musculus (house mouse)EC50 (µMol)1.58490.00242.07168.7096AID548998
Histamine H4 receptorHomo sapiens (human)EC50 (µMol)0.04740.00740.601610.0000AID471098; AID548982; AID548993
Histamine H3 receptorCavia porcellus (domestic guinea pig)EC50 (µMol)1.58490.00150.79321.5849AID548998
Histamine H3 receptorHomo sapiens (human)EC50 (µMol)12.40000.00000.09473.1623AID1300585
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (19)

Processvia Protein(s)Taxonomy
gastric acid secretionHistamine H2 receptorHomo sapiens (human)
immune responseHistamine H2 receptorHomo sapiens (human)
positive regulation of vasoconstrictionHistamine H2 receptorHomo sapiens (human)
G protein-coupled serotonin receptor signaling pathwayHistamine H2 receptorHomo sapiens (human)
chemical synaptic transmissionHistamine H2 receptorHomo sapiens (human)
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messengerHistamine H2 receptorHomo sapiens (human)
inflammatory responseHistamine H1 receptorHomo sapiens (human)
G protein-coupled receptor signaling pathwayHistamine H1 receptorHomo sapiens (human)
phospholipase C-activating G protein-coupled receptor signaling pathwayHistamine H1 receptorHomo sapiens (human)
memoryHistamine H1 receptorHomo sapiens (human)
visual learningHistamine H1 receptorHomo sapiens (human)
regulation of vascular permeabilityHistamine H1 receptorHomo sapiens (human)
positive regulation of vasoconstrictionHistamine H1 receptorHomo sapiens (human)
regulation of synaptic plasticityHistamine H1 receptorHomo sapiens (human)
cellular response to histamineHistamine H1 receptorHomo sapiens (human)
G protein-coupled serotonin receptor signaling pathwayHistamine H1 receptorHomo sapiens (human)
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messengerHistamine H1 receptorHomo sapiens (human)
chemical synaptic transmissionHistamine H1 receptorHomo sapiens (human)
inflammatory responseHistamine H4 receptorHomo sapiens (human)
positive regulation of cytosolic calcium ion concentrationHistamine H4 receptorHomo sapiens (human)
biological_processHistamine H4 receptorHomo sapiens (human)
regulation of MAPK cascadeHistamine H4 receptorHomo sapiens (human)
G protein-coupled serotonin receptor signaling pathwayHistamine H4 receptorHomo sapiens (human)
adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathwayHistamine H4 receptorHomo sapiens (human)
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messengerHistamine H4 receptorHomo sapiens (human)
chemical synaptic transmissionHistamine H4 receptorHomo sapiens (human)
neurotransmitter secretionHistamine H3 receptorHomo sapiens (human)
G protein-coupled serotonin receptor signaling pathwayHistamine H3 receptorHomo sapiens (human)
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messengerHistamine H3 receptorHomo sapiens (human)
chemical synaptic transmissionHistamine H3 receptorHomo sapiens (human)
adenylate cyclase-inhibiting G protein-coupled acetylcholine receptor signaling pathwayHistamine H3 receptorHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (4)

Processvia Protein(s)Taxonomy
histamine receptor activityHistamine H2 receptorHomo sapiens (human)
G protein-coupled serotonin receptor activityHistamine H2 receptorHomo sapiens (human)
neurotransmitter receptor activityHistamine H2 receptorHomo sapiens (human)
histamine receptor activityHistamine H1 receptorHomo sapiens (human)
G protein-coupled serotonin receptor activityHistamine H1 receptorHomo sapiens (human)
neurotransmitter receptor activityHistamine H1 receptorHomo sapiens (human)
histamine receptor activityHistamine H4 receptorHomo sapiens (human)
G protein-coupled serotonin receptor activityHistamine H4 receptorHomo sapiens (human)
G protein-coupled acetylcholine receptor activityHistamine H4 receptorHomo sapiens (human)
histamine receptor activityHistamine H3 receptorHomo sapiens (human)
G protein-coupled acetylcholine receptor activityHistamine H3 receptorHomo sapiens (human)
G protein-coupled serotonin receptor activityHistamine H3 receptorHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (5)

Processvia Protein(s)Taxonomy
plasma membraneHistamine H2 receptorHomo sapiens (human)
synapseHistamine H2 receptorHomo sapiens (human)
plasma membraneHistamine H2 receptorHomo sapiens (human)
dendriteHistamine H2 receptorHomo sapiens (human)
cytosolHistamine H1 receptorHomo sapiens (human)
plasma membraneHistamine H1 receptorHomo sapiens (human)
synapseHistamine H1 receptorHomo sapiens (human)
dendriteHistamine H1 receptorHomo sapiens (human)
plasma membraneHistamine H1 receptorHomo sapiens (human)
plasma membraneHistamine H4 receptorHomo sapiens (human)
plasma membraneHistamine H4 receptorHomo sapiens (human)
dendriteHistamine H4 receptorHomo sapiens (human)
synapseHistamine H4 receptorHomo sapiens (human)
plasma membraneHistamine H3 receptorHomo sapiens (human)
presynapseHistamine H3 receptorHomo sapiens (human)
plasma membraneHistamine H3 receptorHomo sapiens (human)
synapseHistamine H3 receptorHomo sapiens (human)
dendriteHistamine H3 receptorHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (32)

Assay IDTitleYearJournalArticle
AID1300577Intrinsic activity at human histamine H1 receptor expressed in sf9 cell membrane co-expressing RGS4 at 10 uM preincubated for 2 mins followed by [gamma-32P]GTP addition measured after 20 mins by liquid scintillation counting method relative to histamine2016Journal of medicinal chemistry, Apr-14, Volume: 59, Issue:7
Conformational Restriction and Enantioseparation Increase Potency and Selectivity of Cyanoguanidine-Type Histamine H4 Receptor Agonists.
AID548996Selectivity ratio of EC50 for human histamine H4 receptor to EC50 for human histamine H2 receptor2010Bioorganic & medicinal chemistry letters, Dec-15, Volume: 20, Issue:24
Histamine H4 receptor agonists.
AID548982Agonist activity at human recombinant histamine H4 receptor expressed in Sf9 cells coexpressing RGS19, Galphai2, Gbeta1gamma2 by steady-state GTPase activity assay2010Bioorganic & medicinal chemistry letters, Dec-15, Volume: 20, Issue:24
Histamine H4 receptor agonists.
AID1300586Intrinsic activity at human histamine H3 receptor expressed in sf9 cell membrane co-expressing mammalian Galphai2 and Gbeta1gamma2 at 10 uM incubated for 90 mins by [35S]GTPgammaS binding assay relative to histamine2016Journal of medicinal chemistry, Apr-14, Volume: 59, Issue:7
Conformational Restriction and Enantioseparation Increase Potency and Selectivity of Cyanoguanidine-Type Histamine H4 Receptor Agonists.
AID548998Agonist activity at mouse histamine H4 receptor2010Bioorganic & medicinal chemistry letters, Dec-15, Volume: 20, Issue:24
Histamine H4 receptor agonists.
AID471095Agonist activity at human histamine H1 receptor expressed in Sf9 cells coexpressing RGS4 by steady-state GTPase assay2009Journal of medicinal chemistry, Oct-22, Volume: 52, Issue:20
Synthesis and structure-activity relationships of cyanoguanidine-type and structurally related histamine H4 receptor agonists.
AID548997Selectivity ratio of EC50 for human histamine H4 receptor to EC50 for human histamine H3 receptor2010Bioorganic & medicinal chemistry letters, Dec-15, Volume: 20, Issue:24
Histamine H4 receptor agonists.
AID548999Agonist activity at rat histamine H4 receptor2010Bioorganic & medicinal chemistry letters, Dec-15, Volume: 20, Issue:24
Histamine H4 receptor agonists.
AID1300585Agonist activity at human histamine H3 receptor expressed in sf9 cell membrane co-expressing mammalian Galphai2 and Gbeta1gamma2 incubated for 90 mins by [35S]GTPgammaS binding assay2016Journal of medicinal chemistry, Apr-14, Volume: 59, Issue:7
Conformational Restriction and Enantioseparation Increase Potency and Selectivity of Cyanoguanidine-Type Histamine H4 Receptor Agonists.
AID548984Displacement of [125I]iodoaminopotentidine from human histamine H2 receptor expressed in CHO cells2010Bioorganic & medicinal chemistry letters, Dec-15, Volume: 20, Issue:24
Histamine H4 receptor agonists.
AID548980Agonist activity at human recombinant histamine H1 receptor expressed in Sf9 cells coexpressing RGS4 by steady-state GTPase activity assay relative to histamine2010Bioorganic & medicinal chemistry letters, Dec-15, Volume: 20, Issue:24
Histamine H4 receptor agonists.
AID471096Agonist activity at human histamine H2 receptor expressed in Sf9 cells coexpressing GsalphaS protein by steady-state GTPase assay2009Journal of medicinal chemistry, Oct-22, Volume: 52, Issue:20
Synthesis and structure-activity relationships of cyanoguanidine-type and structurally related histamine H4 receptor agonists.
AID87852Evaluated for activity at Histamine H2 receptor in guinea pig ileum1990Journal of medicinal chemistry, Jan, Volume: 33, Issue:1
Histamine H3 ligands: just pharmacological tools or potential therapeutic agents?
AID1300580Intrinsic activity at human histamine H2 receptor expressed in sf9 cell membrane co-expressing Gsalphas at 10 uM incubated for 90 mins by [35S]GTPgammaS binding assay relative to histamine2016Journal of medicinal chemistry, Apr-14, Volume: 59, Issue:7
Conformational Restriction and Enantioseparation Increase Potency and Selectivity of Cyanoguanidine-Type Histamine H4 Receptor Agonists.
AID194444Relative inhibition of [3H]histamine release from pre-loaded slices of rat cerebral cortex1990Journal of medicinal chemistry, Jan, Volume: 33, Issue:1
Histamine H3 ligands: just pharmacological tools or potential therapeutic agents?
AID548993Agonist activity at human histamine H4 receptor expressed in human SK-N-MC cells by CRE-beta galactosidase reporter gene assay2010Bioorganic & medicinal chemistry letters, Dec-15, Volume: 20, Issue:24
Histamine H4 receptor agonists.
AID548985Agonist activity at human histamine H2 receptor expressed in Sf9 cells coexpressing Gsalphas by steady-state GTPase activity assay2010Bioorganic & medicinal chemistry letters, Dec-15, Volume: 20, Issue:24
Histamine H4 receptor agonists.
AID548986Agonist activity at human histamine H2 receptor expressed in Sf9 cells coexpressing Gsalphas by steady-state GTPase activity assay relative to histamine2010Bioorganic & medicinal chemistry letters, Dec-15, Volume: 20, Issue:24
Histamine H4 receptor agonists.
AID471098Agonist activity at human histamine H4 receptor expressed in Sf9 cells coexpressing RGS19 protein by steady-state GTPase assay2009Journal of medicinal chemistry, Oct-22, Volume: 52, Issue:20
Synthesis and structure-activity relationships of cyanoguanidine-type and structurally related histamine H4 receptor agonists.
AID548994Agonist activity at human histamine H4 receptor expressed in human SK-N-MC cells by CRE-beta galactosidase reporter gene assay relative to histamine2010Bioorganic & medicinal chemistry letters, Dec-15, Volume: 20, Issue:24
Histamine H4 receptor agonists.
AID546822Selectivity ratio of EC50 for human histamine H4 receptor to EC50 for mouse histamine H3 receptor2010Bioorganic & medicinal chemistry letters, Dec-15, Volume: 20, Issue:24
Histamine H4 receptor agonists.
AID1300589Intrinsic activity at human histamine H4 receptor expressed in sf9 cell membrane co-expressing mammalian Galphai2 and Gbeta1gamma2 at 10 uM incubated for 90 mins by [35S]GTPgammaS binding assay relative to histamine2016Journal of medicinal chemistry, Apr-14, Volume: 59, Issue:7
Conformational Restriction and Enantioseparation Increase Potency and Selectivity of Cyanoguanidine-Type Histamine H4 Receptor Agonists.
AID586698Selectivity ratio for histamine H4 receptor over histamine H3 receptor2011Journal of medicinal chemistry, Mar-24, Volume: 54, Issue:6
Triazole ligands reveal distinct molecular features that induce histamine H4 receptor affinity and subtly govern H4/H3 subtype selectivity.
AID471099Agonist activity at human histamine H2 receptor expressed in Sf9 cells coexpressing GsalphaS protein at 1 mM by steady-state GTPase assay2009Journal of medicinal chemistry, Oct-22, Volume: 52, Issue:20
Synthesis and structure-activity relationships of cyanoguanidine-type and structurally related histamine H4 receptor agonists.
AID548987Displacement of [3H]Nalpha-methylhistamine from human histamine H3 receptor expressed in human SK-N-MC cells2010Bioorganic & medicinal chemistry letters, Dec-15, Volume: 20, Issue:24
Histamine H4 receptor agonists.
AID548995Selectivity ratio of EC50 for human histamine H4 receptor to EC50 for human histamine H1 receptor2010Bioorganic & medicinal chemistry letters, Dec-15, Volume: 20, Issue:24
Histamine H4 receptor agonists.
AID548983Agonist activity at human recombinant histamine H4 receptor expressed in Sf9 cells coexpressing RGS19, Galphai2, Gbeta1gamma2 by steady-state GTPase activity assay relative to histamine2010Bioorganic & medicinal chemistry letters, Dec-15, Volume: 20, Issue:24
Histamine H4 receptor agonists.
AID548981Displacement of [3H]-histamine from human histamine H4 receptor expressed in Sf9 cells coexpressing RGS19, Galphai2, Gbeta1gamma22010Bioorganic & medicinal chemistry letters, Dec-15, Volume: 20, Issue:24
Histamine H4 receptor agonists.
AID86257Evaluated for activity at Histamine H1 receptor in guinea pig ileum1990Journal of medicinal chemistry, Jan, Volume: 33, Issue:1
Histamine H3 ligands: just pharmacological tools or potential therapeutic agents?
AID1798265H4R Radioligand Binding Assay from Article 10.1124/jpet.105.087965: \\Evaluation of histamine H1-, H2-, and H3-receptor ligands at the human histamine H4 receptor: identification of 4-methylhistamine as the first potent and selective H4 receptor agonist.\\2005The Journal of pharmacology and experimental therapeutics, Sep, Volume: 314, Issue:3
Evaluation of histamine H1-, H2-, and H3-receptor ligands at the human histamine H4 receptor: identification of 4-methylhistamine as the first potent and selective H4 receptor agonist.
AID1346055Human H4 receptor (Histamine receptors)2006British journal of pharmacology, Apr, Volume: 147, Issue:7
Compared pharmacology of human histamine H3 and H4 receptors: structure-activity relationships of histamine derivatives.
AID1346055Human H4 receptor (Histamine receptors)2005The Journal of pharmacology and experimental therapeutics, Sep, Volume: 314, Issue:3
Evaluation of histamine H1-, H2-, and H3-receptor ligands at the human histamine H4 receptor: identification of 4-methylhistamine as the first potent and selective H4 receptor agonist.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (120)

TimeframeStudies, This Drug (%)All Drugs %
pre-199058 (48.33)18.7374
1990's21 (17.50)18.2507
2000's13 (10.83)29.6817
2010's25 (20.83)24.3611
2020's3 (2.50)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 23.06

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be moderate demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index23.06 (24.57)
Research Supply Index4.82 (2.92)
Research Growth Index4.55 (4.65)
Search Engine Demand Index26.67 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (23.06)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials1 (0.82%)5.53%
Reviews1 (0.82%)6.00%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Other120 (98.36%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]