Page last updated: 2024-12-05

alpha-methylhistamine

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Description

Alpha-methylhistamine (α-methylhistamine) is a synthetic histamine analog that acts as a potent and selective H3 receptor agonist. It is not found naturally in the body. α-methylhistamine is used in research to study the role of H3 receptors in the central nervous system. It is believed to play a role in cognitive function, sleep-wake cycles, and appetite regulation. α-methylhistamine has been shown to have various effects, including reducing histamine release, inhibiting neurotransmitter release, and altering neuronal activity. It is often used in animal models to investigate the effects of H3 receptor activation on different physiological processes. Research on α-methylhistamine has contributed to the understanding of the role of H3 receptors in various biological functions, providing potential targets for the development of new drugs for conditions such as Alzheimer's disease, narcolepsy, and obesity.'

alpha-methylhistamine: a histamine H3 receptor agonist; RN given refers to parent cpd without isomeric designation [Medical Subject Headings (MeSH), National Library of Medicine, extracted Dec-2023]

alpha-methylhistamine : An aralkylamino compound that is histamine bearing a methyl substituent at the alpha-position. [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]

(R)-alpha-methylhistamine : An aralkylamino compound that is histamine bearing a methyl substituent at the alpha-position (the R-enantiomer). [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 CID3615
CHEMBL ID116655
CHEBI ID74759
SCHEMBL ID396350
SCHEMBL ID12328968
MeSH IDM0189313
PubMed CID156615
CHEMBL ID268229
CHEBI ID73337
SCHEMBL ID73663
SCHEMBL ID4155130
MeSH IDM0189313

Synonyms (79)

Synonym
AKOS012051956
6986-90-9
PDSP2_000181
PDSP1_000182
1h-imidazole-4-ethanamine, alpha-methyl-
alpha-methylhistamine
L000527
1-(1h-imidazol-5-yl)propan-2-amine
chebi:74759 ,
CHEMBL116655
NI35063000
niosh/ni3506300
imidazole, 4-(2-aminopropyl)-
4-(2-aminopropyl)imidazole
1h-imidazole-5-ethanamine,a-methyl-
SCHEMBL396350
SCHEMBL12328968
1-(1h-imidazol-4-yl)-2-propanamine #
1h-imidazole-4-ethanamine, .alpha.-methyl-
XNQIOISZPFVUFG-UHFFFAOYSA-N
.alpha.-methylhistamine
2-(1h-imidazol-4-yl)-1-methyl-ethylamine
1-(1h-imidazol-4-yl)propan-2-amine
Q4734911
DTXSID80990132
SB38376
CS-0455026
EN300-254952
(r)-alpha-meha
[3h]-r-alpha-methylhistamine
(r)-[3h]alpha-methylhistamine
gtpl1237
[3h](r)-alpha-methylhistamine
gtpl1236
PDSP1_000542
bdbm22904
(r)-alpha-methylhistamine
alpha-methylhistamine-r
alpha-methylhistane-r
r-alpha-methylhistamine
ramh
(2r)-1-(1h-imidazol-5-yl)propan-2-amine
chembl268229 ,
PDSP1_000541
PDSP2_000533
tocris-0569
NCGC00024656-01
PDSP1_000535
LOPAC0_000618
PDSP2_000507
PDSP2_000539
alpha methylhistamine
NCGC00024656-03
1h-imidazole-4-ethanamine, alpha-methyl-, (alphar)-
NCGC00024656-02
NCGC00024656-04
chebi:73337 ,
AKOS006343508
(2r)-1-(3h-imidazol-4-yl)propan-2-amine
CCG-204707
75614-87-8
r(-)-alpha-methylhistamine.2hbr
(r)alpha-me-histamine
(r)-(-)-alpha-methylhistamine
(2r)-1-(1h-imidazol-4-yl)propan-2-amine
(r)-(-)-4-(2-aminopropyl)imidazole
SCHEMBL73663
r(-)alpha methylhistamine
(r)-2-(3h-imidazol-4-yl)-1-methyl-ethylamine
XNQIOISZPFVUFG-RXMQYKEDSA-N
SCHEMBL4155130
DTXSID00873372
(r)-1-(1h-imidazol-5-yl)propan-2-amine
SDCCGSBI-0050600.P002
NCGC00024656-08
alpha-methylhistamine-dihydrobromide-(r)-(-)
bdbm50215536
r-2-(1h-imidazol-4-yl)-1-methyl-ethylamine
EN300-1817458

Research Excerpts

Pharmacokinetics

ExcerptReferenceRelevance
" Moreover, the pharmacokinetic parameters of the prodrugs were investigated in vitro as well as in vivo."( Synthesis, X-ray crystallography, and pharmacokinetics of novel azomethine prodrugs of (R)-alpha-methylhistamine: highly potent and selective histamine H3 receptor agonists.
Garbarg, M; Krause, M; Lipp, R; Luger, P; Rouleau, A; Schunack, W; Schwart, JC; Stark, H, 1995
)
0.51

Bioavailability

ExcerptReferenceRelevance
" Azomethine derivatives of the highly potent histamine H3 receptor agonist (R)-alpha-methylhistamine (1) were prepared as lipophilic prodrugs to improve the bioavailability of the hydrophilic drug, particularly its entry into the brain."( Synthesis, X-ray crystallography, and pharmacokinetics of novel azomethine prodrugs of (R)-alpha-methylhistamine: highly potent and selective histamine H3 receptor agonists.
Garbarg, M; Krause, M; Lipp, R; Luger, P; Rouleau, A; Schunack, W; Schwart, JC; Stark, H, 1995
)
0.74
" It was shown that prodrug approaches based on an initial enzyme-catalyzed liberation step are successfully applicable to different pro-moieties for improved bioavailability and prolonged half-live."( Enzyme-catalyzed prodrug approaches for the histamine H3-receptor agonist (R)-alpha-methylhistamine.
Garbarg, M; Krause, M; Rouleau, A; Schunack, W; Schwartz, JC; Stark, H, 2001
)
0.54
"CEP-32215 is a new, potent, selective, and orally bioavailable inverse agonist of the histamine H3 receptor (H3R) with drug-like properties."( 3-(1'-Cyclobutylspiro[4H-1,3-benzodioxine-2,4'-piperidine]-6-yl)-5,5-dimethyl-1,4-dihydropyridazin-6-one (CEP-32215), a new wake-promoting histamine H3 antagonist/inverse agonist.
Aimone, LD; Ator, MA; Bacon, ER; Gruner, JA; Hudkins, RL; Marino, MJ; Mathiasen, JR; Raddatz, R; Williams, M, 2016
)
0.43

Dosage Studied

ExcerptRelevanceReference
" Treatment with centrally acting H1 antagonists (dimethindene and promethazine) in non-sedative dosage diminished the PTZ seizure threshold significantly; no changes were seen after treatment with H2 and H3 antagonists (oxmetidine, ranitidine, zolantidine or thioperamide) and a H3 agonist (R-alpha-methylhistamine)."( Histamine in brain--its role in regulation of seizure susceptibility.
Frey, HH; Hashem, A; Scherkl, R,
)
0.31
"), which facilitates histamine release, significantly shifted the methamphetamine dose-response curve to the left when tested together with different doses of methamphetamine and markedly extended the time-course of methamphetamine's discriminative-stimulus effects."( Potentiation of the discriminative-stimulus effects of methamphetamine by the histamine H3 receptor antagonist thioperamide in rats.
Goldberg, SR; Munzar, P; Nosál, R, 1998
)
0.3
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Roles (2)

RoleDescription
H3-receptor agonistA histamine agonist that binds to and activates histamine H3-receptors.
animal metaboliteAny eukaryotic metabolite produced during a metabolic reaction in animals that include diverse creatures from sponges, insects to mammals.
H3-receptor agonistA histamine agonist that binds to and activates histamine H3-receptors.
[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
aralkylamino compoundAn organic amino compound in which an aminoalkyl group is linked to an arene.
imidazolesA five-membered organic heterocycle containing two nitrogen atoms at positions 1 and 3, or any of its derivatives; compounds containing an imidazole skeleton.
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 (15)

Potency Measurements

ProteinTaxonomyMeasurementAverage (µ)Min (ref.)Avg (ref.)Max (ref.)Bioassay(s)
thioredoxin reductaseRattus norvegicus (Norway rat)Potency8.53980.100020.879379.4328AID588453; AID588456
TDP1 proteinHomo sapiens (human)Potency26.10110.000811.382244.6684AID686978; AID686979
aldehyde dehydrogenase 1 family, member A1Homo sapiens (human)Potency39.81070.011212.4002100.0000AID1030
arylsulfatase AHomo sapiens (human)Potency33.80781.069113.955137.9330AID720538
alpha-galactosidaseHomo sapiens (human)Potency63.09574.466818.391635.4813AID2107
euchromatic histone-lysine N-methyltransferase 2Homo sapiens (human)Potency25.11890.035520.977089.1251AID504332
vitamin D3 receptor isoform VDRAHomo sapiens (human)Potency79.43280.354828.065989.1251AID504847
chromobox protein homolog 1Homo sapiens (human)Potency7.07950.006026.168889.1251AID488953
lethal factor (plasmid)Bacillus anthracis str. A2012Potency12.58930.020010.786931.6228AID912
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Histamine H1 receptorCavia porcellus (domestic guinea pig)Ki10.00000.00261.783210.0000AID86739
Metabotropic glutamate receptor 5Rattus norvegicus (Norway rat)Ki0.00050.00050.19643.7600AID479096
Histamine H4 receptorHomo sapiens (human)Ki833,737,981,952.16640.00060.478710.0000AID1798265; AID404336; AID548981; AID89900; AID90039
Histamine H3 receptorCavia porcellus (domestic guinea pig)Ki0.00080.00010.00300.0126AID86442; AID88660
Histamine H3 receptorRattus norvegicus (Norway rat)IC50 (µMol)0.00150.00150.88911.3000AID566262
Histamine H3 receptorHomo sapiens (human)IC50 (µMol)0.00230.00050.46685.9000AID751670
Histamine H3 receptorHomo sapiens (human)Ki0.00790.00010.33998.5110AID1798266; AID1829881; AID1829899; AID408541; AID479096; AID548987; AID599203; AID751670; AID86456; AID86459; AID86619; AID89882
[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)
Metabotropic glutamate receptor 5Rattus norvegicus (Norway rat)EC50 (µMol)0.00280.00151.653710.0000AID479097
Histamine H4 receptorHomo sapiens (human)EC50 (µMol)0.87650.00740.601610.0000AID548993; AID90035
Histamine H3 receptorHomo sapiens (human)EC50 (µMol)0.01090.00000.09473.1623AID1690421; AID479097; AID548991; AID86478
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Other Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Histamine H3 receptorCavia porcellus (domestic guinea pig)KH0.00430.00270.00350.0043AID88654
Histamine H3 receptorCavia porcellus (domestic guinea pig)KL0.22000.22000.61501.0100AID88655
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (9)

Processvia Protein(s)Taxonomy
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 (3)

Processvia Protein(s)Taxonomy
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 (4)

Processvia Protein(s)Taxonomy
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 (104)

Assay IDTitleYearJournalArticle
AID504836Inducers of the Endoplasmic Reticulum Stress Response (ERSR) in human glioma: Validation2002The Journal of biological chemistry, Apr-19, Volume: 277, Issue:16
Sustained ER Ca2+ depletion suppresses protein synthesis and induces activation-enhanced cell death in mast cells.
AID1347057CD47-SIRPalpha protein protein interaction - LANCE assay qHTS validation2019PloS one, , Volume: 14, Issue:7
Quantitative high-throughput screening assays for the discovery and development of SIRPα-CD47 interaction inhibitors.
AID1508630Primary qHTS for small molecule stabilizers of the endoplasmic reticulum resident proteome: Secreted ER Calcium Modulated Protein (SERCaMP) assay2021Cell reports, 04-27, Volume: 35, Issue:4
A target-agnostic screen identifies approved drugs to stabilize the endoplasmic reticulum-resident proteome.
AID1347082qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lassa (LASV) Arenavirus: LASV Primary Screen - GLuc reporter signal2020Antiviral research, 01, Volume: 173A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID1347059CD47-SIRPalpha protein protein interaction - Alpha assay qHTS validation2019PloS one, , Volume: 14, Issue:7
Quantitative high-throughput screening assays for the discovery and development of SIRPα-CD47 interaction inhibitors.
AID1347049Natriuretic polypeptide receptor (hNpr1) antagonism - Pilot screen2019Science translational medicine, 07-10, Volume: 11, Issue:500
Inhibition of natriuretic peptide receptor 1 reduces itch in mice.
AID504812Inverse Agonists of the Thyroid Stimulating Hormone Receptor: HTS campaign2010Endocrinology, Jul, Volume: 151, Issue:7
A small molecule inverse agonist for the human thyroid-stimulating hormone receptor.
AID504810Antagonists of the Thyroid Stimulating Hormone Receptor: HTS campaign2010Endocrinology, Jul, Volume: 151, Issue:7
A small molecule inverse agonist for the human thyroid-stimulating hormone receptor.
AID1347151Optimization of GU AMC qHTS for Zika virus inhibitors: Unlinked NS2B-NS3 protease assay2020Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49
Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID1347050Natriuretic polypeptide receptor (hNpr2) antagonism - Pilot subtype selectivity assay2019Science translational medicine, 07-10, Volume: 11, Issue:500
Inhibition of natriuretic peptide receptor 1 reduces itch in mice.
AID1347410qHTS for inhibitors of adenylyl cyclases using a fission yeast platform: a pilot screen against the NCATS LOPAC library2019Cellular signalling, 08, Volume: 60A fission yeast platform for heterologous expression of mammalian adenylyl cyclases and high throughput screening.
AID1347405qHTS to identify inhibitors of the type 1 interferon - major histocompatibility complex class I in skeletal muscle: primary screen against the NCATS LOPAC collection2020ACS chemical biology, 07-17, Volume: 15, Issue:7
High-Throughput Screening to Identify Inhibitors of the Type I Interferon-Major Histocompatibility Complex Class I Pathway in Skeletal Muscle.
AID588349qHTS for Inhibitors of ATXN expression: Validation of Cytotoxic Assay
AID588378qHTS for Inhibitors of ATXN expression: Validation
AID1347086qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lymphocytic Choriomeningitis Arenaviruses (LCMV): LCMV Primary Screen - GLuc reporter signal2020Antiviral research, 01, Volume: 173A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID1347045Natriuretic polypeptide receptor (hNpr1) antagonism - Pilot counterscreen GloSensor control cell line2019Science translational medicine, 07-10, Volume: 11, Issue:500
Inhibition of natriuretic peptide receptor 1 reduces itch in mice.
AID1347058CD47-SIRPalpha protein protein interaction - HTRF assay qHTS validation2019PloS one, , Volume: 14, Issue:7
Quantitative high-throughput screening assays for the discovery and development of SIRPα-CD47 interaction inhibitors.
AID1347083qHTS for Inhibitors of the Functional Ribonucleoprotein Complex (vRNP) of Lassa (LASV) Arenavirus: Viability assay - alamar blue signal for LASV Primary Screen2020Antiviral research, 01, Volume: 173A cell-based, infectious-free, platform to identify inhibitors of lassa virus ribonucleoprotein (vRNP) activity.
AID1347154Primary screen GU AMC qHTS for Zika virus inhibitors2020Proceedings of the National Academy of Sciences of the United States of America, 12-08, Volume: 117, Issue:49
Therapeutic candidates for the Zika virus identified by a high-throughput screen for Zika protease inhibitors.
AID232567Ratio of ED50 of H1 receptor to that of ED50 of H3 receptor was determined1998Bioorganic & medicinal chemistry letters, Feb-03, Volume: 8, Issue:3
Trans-4-methyl-3-imidazoyl pyrrolidine as a potent, highly selective histamine H3 receptor agonist in vivo.
AID89872Affinity for histamine H3 receptor in rat cerebral cortex.1999Journal of medicinal chemistry, Apr-08, Volume: 42, Issue:7
Synthesis and in vitro pharmacology of a series of new chiral histamine H3-receptor ligands: 2-(R and S)-Amino-3-(1H-imidazol-4(5)-yl)propyl ether derivatives.
AID88615Histamine level after treatment was determined in colon.1990Journal of medicinal chemistry, Jan, Volume: 33, Issue:1
Histamine H3 ligands: just pharmacological tools or potential therapeutic agents?
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.
AID89882Inhibition of Histamine H3 receptor2003Journal of medicinal chemistry, May-08, Volume: 46, Issue:10
Cyclopropane-based conformational restriction of histamine. (1S,2S)-2-(2-aminoethyl)-1-(1H-imidazol-4-yl)cyclopropane, a highly selective agonist for the histamine H3 receptor, having a cis-cyclopropane structure.
AID88654H3 receptor agonistic activity of the compound1994Journal of medicinal chemistry, Feb-04, Volume: 37, Issue:3
A new potent and selective histamine H3 receptor agonist, 4-(1H-imidazol-4-ylmethyl)piperidine.
AID548991Agonist activity at human histamine H3 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.
AID86413Effective dose by H1-mediated bronchospasm in guinea pig1998Bioorganic & medicinal chemistry letters, Feb-03, Volume: 8, Issue:3
Trans-4-methyl-3-imidazoyl pyrrolidine as a potent, highly selective histamine H3 receptor agonist in vivo.
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?
AID86620Selectivity is the ratio of inhibitory activity against Histamine H3 receptor to that of Histamine H4 receptor2003Journal of medicinal chemistry, Dec-04, Volume: 46, Issue:25
Synthesis and structure-activity relationships of conformationally constrained histamine H(3) 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.
AID181166Histamine level after treatment was determined in spleen1990Journal of medicinal chemistry, Jan, Volume: 33, Issue:1
Histamine H3 ligands: just pharmacological tools or potential therapeutic agents?
AID86739Binding affinity against H1 receptor1995Journal of medicinal chemistry, May-12, Volume: 38, Issue:10
A novel pyrrolidine analog of histamine as a potent, highly selective histamine H3 receptor agonist.
AID86455Intrinsic activity determined towards Histamine H3 receptor2003Journal of medicinal chemistry, Dec-04, Volume: 46, Issue:25
Synthesis and structure-activity relationships of conformationally constrained histamine H(3) receptor agonists.
AID404336Displacement of [3H]histamine from human histamine H4 receptor expressed in SK-NM-C cells2008Journal of medicinal chemistry, Jun-12, Volume: 51, Issue:11
Discovery of novel human histamine H4 receptor ligands by large-scale structure-based virtual screening.
AID479096Displacement of [3H[N-alpha-methylhistamine form human recombinant histamine H3 receptor expressed in CHO cells after 1 hr by liquid scintillation counting2010Journal of medicinal chemistry, May-13, Volume: 53, Issue:9
Role of hydrophobic substituents on the terminal nitrogen of histamine in receptor binding and agonist activity: development of an orally active histamine type 3 receptor agonist and evaluation of its antistress activity in mice.
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?
AID479097Agonist activity at human recombinant histamine H3 receptor expressed in CHO cells assessed as [35S]GTPgammaS binding after 1 hr by liquid scintillation counting2010Journal of medicinal chemistry, May-13, Volume: 53, Issue:9
Role of hydrophobic substituents on the terminal nitrogen of histamine in receptor binding and agonist activity: development of an orally active histamine type 3 receptor agonist and evaluation of its antistress activity in mice.
AID88655KL value determined on H3 receptor1994Journal of medicinal chemistry, Feb-04, Volume: 37, Issue:3
A new potent and selective histamine H3 receptor agonist, 4-(1H-imidazol-4-ylmethyl)piperidine.
AID765075Anticonvulsant activity in Wistar rat assessed as protection against maximum electric shock-induced tonic hind limb extension at 10 mg/kg, ip2013Bioorganic & medicinal chemistry letters, Sep-01, Volume: 23, Issue:17
Anticonvulsant properties of histamine H3 receptor ligands belonging to N-substituted carbamates of imidazopropanol.
AID1829899Binding affinity in Nluc-hH3R assessed in HEK293T cells by NanoBRET binding assay2021Journal of medicinal chemistry, 08-12, Volume: 64, Issue:15
A Versatile Sub-Nanomolar Fluorescent Ligand Enables NanoBRET Binding Studies and Single-Molecule Microscopy at the Histamine H
AID89898Intrinsic activity for Histamine H4 receptor2003Journal of medicinal chemistry, Dec-04, Volume: 46, Issue:25
Synthesis and structure-activity relationships of conformationally constrained histamine H(3) receptor agonists.
AID88660Binding affinity against Histamine H3 receptor1995Journal of medicinal chemistry, May-12, Volume: 38, Issue:10
A novel pyrrolidine analog of histamine as a potent, highly selective histamine H3 receptor agonist.
AID77084Effective dose was tested in vivo for 50% inhibition by an electrically induced CNS hypertension model after iv administration.1995Journal of medicinal chemistry, May-12, Volume: 38, Issue:10
A novel pyrrolidine analog of histamine as a potent, highly selective histamine H3 receptor agonist.
AID86305In vitro histamine H3 receptor antagonist activity was determined on guinea pig jejunum2000Journal of medicinal chemistry, May-04, Volume: 43, Issue:9
Characterization of the binding site of the histamine H(3) receptor. 2. Synthesis, in vitro pharmacology, and QSAR of a series of monosubstituted benzyl analogues of thioperamide.
AID181162Histamine level after treatment was determined in cerebral cortex1990Journal of medicinal chemistry, Jan, Volume: 33, Issue:1
Histamine H3 ligands: just pharmacological tools or potential therapeutic agents?
AID86456Antagonist potency against human histamine H3 receptor expressed in CHO cells was determined by GTPgamma-S-assay2004Journal of medicinal chemistry, May-20, Volume: 47, Issue:11
1-alkyl-4-acylpiperazines as a new class of imidazole-free histamine H(3) receptor antagonists.
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.
AID751670Displacement of [3H]N-alpha-methylhistamine from human recombinant histamine H3 receptor expressed in CHOK1 cells after 2 hrs2013Bioorganic & medicinal chemistry letters, Mar-15, Volume: 23, Issue:6
Cinnamides as selective small-molecule inhibitors of a cellular model of breast cancer stem cells.
AID181161Histamine level after treatment was determined in adbominal skin.1990Journal of medicinal chemistry, Jan, Volume: 33, Issue:1
Histamine H3 ligands: just pharmacological tools or potential therapeutic agents?
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.
AID181165Histamine level after treatment was determined in lung.1990Journal of medicinal chemistry, Jan, Volume: 33, Issue:1
Histamine H3 ligands: just pharmacological tools or potential therapeutic agents?
AID73672In vitro effective concentration for H-3-mediated contraction of guinea pig ileum1998Bioorganic & medicinal chemistry letters, Feb-03, Volume: 8, Issue:3
Trans-4-methyl-3-imidazoyl pyrrolidine as a potent, highly selective histamine H3 receptor agonist in vivo.
AID1690421Agonist activity at human H3 receptor expressed in HEK293 cells preincubated for 30 mins followed by [35S]-GTPgammaS addition and measured after 30 mins by liquid scintillation counting method2020European journal of medicinal chemistry, Apr-01, Volume: 191Novel pyrrolidinone derivative lacks claimed histamine H
AID751736Displacement of [3H]N-alpha-methylhistamine from human recombinant histamine H3 receptor expressed in CHOK1 cells at 10 uM after 2 hrs relative to control2013Bioorganic & medicinal chemistry letters, Mar-15, Volume: 23, Issue:6
Cinnamides as selective small-molecule inhibitors of a cellular model of breast cancer stem cells.
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?
AID73671Effective dose by H3-mediated bronchospasm in guinea pig1998Bioorganic & medicinal chemistry letters, Feb-03, Volume: 8, Issue:3
Trans-4-methyl-3-imidazoyl pyrrolidine as a potent, highly selective histamine H3 receptor agonist in vivo.
AID89730Binding affinity for Histamine H3 receptor1999Journal of medicinal chemistry, Apr-08, Volume: 42, Issue:7
Synthesis and in vitro pharmacology of a series of new chiral histamine H3-receptor ligands: 2-(R and S)-Amino-3-(1H-imidazol-4(5)-yl)propyl ether derivatives.
AID86619Inhibitory activity measured by [3H]- N alpha- methyl-histamine binding to membranes of SK-N-MC cells expressing the human Histamine H3 receptor2003Journal of medicinal chemistry, Dec-04, Volume: 46, Issue:25
Synthesis and structure-activity relationships of conformationally constrained histamine H(3) receptor agonists.
AID86915Binding affinity against H1 receptor from guinea pig ileum1995Journal of medicinal chemistry, May-12, Volume: 38, Issue:10
A novel pyrrolidine analog of histamine as a potent, highly selective histamine H3 receptor agonist.
AID74454Tested for activity of compound against neurogenic contractions of guinea pig jejunum; Potent antagonist2004Journal of medicinal chemistry, Jun-03, Volume: 47, Issue:12
Meta-substituted aryl(thio)ethers as potent partial agonists (or antagonists) for the histamine H3 receptor lacking a nitrogen atom in the side chain.
AID77082Effective dose was tested in vivo for 50% inhibition by an H1 histamine-mediated bronchospasm after iv administration in guinea pig1995Journal of medicinal chemistry, May-12, Volume: 38, Issue:10
A novel pyrrolidine analog of histamine as a potent, highly selective histamine H3 receptor agonist.
AID408551Agonist activity at histamine H3 receptor in rat cortex2008Journal of medicinal chemistry, May-22, Volume: 51, Issue:10
4-benzyl-1H-imidazoles with oxazoline termini as histamine H3 receptor agonists.
AID566262Inhibition of rat histamine H3 receptor2010Bioorganic & medicinal chemistry, Nov-01, Volume: 18, Issue:21
Discovery of {1-[4-(2-{hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl}-1H-benzimidazol-1-yl)piperidin-1-yl]cyclooctyl}methanol, systemically potent novel non-peptide agonist of nociceptin/orphanin FQ receptor as analgesic for the treatment of neuropathic pain: de
AID548992Agonist activity at human histamine H3 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.
AID86737Binding affinity to H-1 receptor was determined in guinea pig brain tissue using [3H]- N alpha-methylhistamine ligand1998Bioorganic & medicinal chemistry letters, Feb-03, Volume: 8, Issue:3
Trans-4-methyl-3-imidazoyl pyrrolidine as a potent, highly selective histamine H3 receptor agonist in vivo.
AID181164Histamine level after treatment was determined in hypothalamus.1990Journal of medicinal chemistry, Jan, Volume: 33, Issue:1
Histamine H3 ligands: just pharmacological tools or potential therapeutic agents?
AID90035Inhibitory activity determined by the inhibition of cAMP- stimulated beta-galactosidase transcription in SK-N-MC cells expressing the human Histamine H4 receptor2003Journal of medicinal chemistry, Dec-04, Volume: 46, Issue:25
Synthesis and structure-activity relationships of conformationally constrained histamine H(3) receptor agonists.
AID1829881Binding affinity in Nluc-hH3R assessed in HEK293 cells by NanoBRET binding assay2021Journal of medicinal chemistry, 08-12, Volume: 64, Issue:15
A Versatile Sub-Nanomolar Fluorescent Ligand Enables NanoBRET Binding Studies and Single-Molecule Microscopy at the Histamine H
AID86919In vitro effective concentration for H1-mediated contraction of guinea pig ileum1998Bioorganic & medicinal chemistry letters, Feb-03, Volume: 8, Issue:3
Trans-4-methyl-3-imidazoyl pyrrolidine as a potent, highly selective histamine H3 receptor agonist in vivo.
AID79985Compound was tested for inhibition of histamine H3-receptor mediated neurogenic contractions in the isolated guinea pig ileum assay; Full agonist1999Bioorganic & medicinal chemistry letters, Jul-05, Volume: 9, Issue:13
From histamine to imidazolylalkyl-sulfonamides: the design of a novel series of histamine H3-receptor antagonists.
AID86442Binding affinity towards histamine H3 receptor using [3H](R)-alpha-methylhistamine as radioligand in guinea pig cortical homogenates1999Bioorganic & medicinal chemistry letters, Jul-05, Volume: 9, Issue:13
From histamine to imidazolylalkyl-sulfonamides: the design of a novel series of histamine H3-receptor antagonists.
AID408541Displacement of [3H]N-alpha-methylhistamine from human histamine H3 receptor expressed in CHO cells2008Journal of medicinal chemistry, May-22, Volume: 51, Issue:10
4-benzyl-1H-imidazoles with oxazoline termini as histamine H3 receptor agonists.
AID88658Binding affinity of compound towards Histamine H3 receptor was determined in guinea pig brain tissue using [3H]- N alpha-methylhistamine radioligand1998Bioorganic & medicinal chemistry letters, Feb-03, Volume: 8, Issue:3
Trans-4-methyl-3-imidazoyl pyrrolidine as a potent, highly selective histamine H3 receptor agonist in vivo.
AID599203Displacement of [3H]N-alpha-methylhistamine from human histamine H3 receptor expressed in SK-N-MC cells2009European journal of medicinal chemistry, Nov, Volume: 44, Issue:11
Heterocyclic replacement of the central phenyl core of diamine-based histamine H3 receptor antagonists.
AID86443Binding affinity towards histamine H3 receptor using [3H](R)-alpha-methylhistamine as radioligand in guinea pig ileum LMMP homogenates1999Bioorganic & medicinal chemistry letters, Jul-05, Volume: 9, Issue:13
From histamine to imidazolylalkyl-sulfonamides: the design of a novel series of histamine H3-receptor antagonists.
AID86301pD2 values against H3 receptor of guinea pig jejunum were determined.1995Journal of medicinal chemistry, Jan-20, Volume: 38, Issue:2
Homologs of histamine as histamine H3 receptor antagonists: a new potent and selective H3 antagonist, 4(5)-(5-aminopentyl)-1H-imidazole.
AID86622Activity against Histamine H3 receptor mediated inhibition of [3H]norepinephrine release from mouse brain; Partial agonist2004Journal of medicinal chemistry, Jun-03, Volume: 47, Issue:12
Meta-substituted aryl(thio)ethers as potent partial agonists (or antagonists) for the histamine H3 receptor lacking a nitrogen atom in the side chain.
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.
AID86459Binding affinity to the human histamine H3 receptor2003Journal of medicinal chemistry, Sep-11, Volume: 46, Issue:19
The first potent and selective non-imidazole human histamine H4 receptor antagonists.
AID86478Inhibitory activity determined by the inhibition of cAMP- stimulated beta-galactosidase transcription in SK-N-MC cells expressing the human Histamine H3 receptor2003Journal of medicinal chemistry, Dec-04, Volume: 46, Issue:25
Synthesis and structure-activity relationships of conformationally constrained histamine H(3) receptor agonists.
AID89900Binding affinity to the human histamine H4 receptor2003Journal of medicinal chemistry, Sep-11, Volume: 46, Issue:19
The first potent and selective non-imidazole human histamine H4 receptor antagonists.
AID24868pD2 value was determined on jejunum preparations of eight different animals1994Journal of medicinal chemistry, Feb-04, Volume: 37, Issue:3
A new potent and selective histamine H3 receptor agonist, 4-(1H-imidazol-4-ylmethyl)piperidine.
AID86639Inhibition of the specific binding of [3H](R)-alpha-methylhistamine ([3H]RMHA) to Histamine H3 receptor in rat brain membranes at 10e-8 M2002Bioorganic & medicinal chemistry letters, Dec-16, Volume: 12, Issue:24
Synthesis and biological evaluation of novel 2-(1H-imidazol-4-yl)cyclopropane carboxylic acids: key intermediates for H3 histamine receptor ligands.
AID86302Binding affinity against H3 receptor from guinea pig ileum1995Journal of medicinal chemistry, May-12, Volume: 38, Issue:10
A novel pyrrolidine analog of histamine as a potent, highly selective histamine H3 receptor agonist.
AID90039Inhibitory activity measured by [3H]- N alpha- methyl-histamine binding to membranes of SK-N-MC cells expressing the human Histamine H4 receptor2003Journal of medicinal chemistry, Dec-04, Volume: 46, Issue:25
Synthesis and structure-activity relationships of conformationally constrained histamine H(3) receptor agonists.
AID1346017Rat H3 receptor (Histamine receptors)2000British journal of pharmacology, Dec, Volume: 131, Issue:7
Distinct pharmacology of rat and human histamine H(3) receptors: role of two amino acids in the third transmembrane domain.
AID1346055Human H4 receptor (Histamine receptors)2001Molecular pharmacology, Mar, Volume: 59, Issue:3
Cloning and pharmacological characterization of a fourth histamine receptor (H(4)) expressed in bone marrow.
AID1346028Rat H4 receptor (Histamine receptors)2001The Journal of pharmacology and experimental therapeutics, Oct, Volume: 299, Issue:1
Comparison of human, mouse, rat, and guinea pig histamine H4 receptors reveals substantial pharmacological species variation.
AID1346055Human H4 receptor (Histamine receptors)2001The Journal of pharmacology and experimental therapeutics, Mar, Volume: 296, Issue:3
Cloning and characterization of a novel human histamine receptor.
AID1346107Human H3 receptor (Histamine receptors)2001Molecular pharmacology, Mar, Volume: 59, Issue:3
Cloning and pharmacological characterization of a fourth histamine receptor (H(4)) expressed in bone marrow.
AID1346055Human H4 receptor (Histamine receptors)2001The Journal of pharmacology and experimental therapeutics, Oct, Volume: 299, Issue:1
Comparison of human, mouse, rat, and guinea pig histamine H4 receptors reveals substantial pharmacological species variation.
AID1346044Mouse H4 receptor (Histamine receptors)2001The Journal of pharmacology and experimental therapeutics, Oct, Volume: 299, Issue:1
Comparison of human, mouse, rat, and guinea pig histamine H4 receptors reveals substantial pharmacological species variation.
AID1346107Human H3 receptor (Histamine receptors)2001The Journal of pharmacology and experimental therapeutics, Dec, Volume: 299, Issue:3
Constitutive activity of histamine h(3) receptors stably expressed in SK-N-MC cells: display of agonism and inverse agonism by H(3) antagonists.
AID1346017Rat H3 receptor (Histamine receptors)2002European journal of pharmacology, Oct-18, Volume: 453, Issue:1
Characteristics of recombinantly expressed rat and human histamine H3 receptors.
AID1346107Human H3 receptor (Histamine receptors)2000British journal of pharmacology, Dec, Volume: 131, Issue:7
Distinct pharmacology of rat and human histamine H(3) receptors: role of two amino acids in the third transmembrane domain.
AID1346088Mouse H3 receptor (Histamine receptors)2003European journal of pharmacology, Apr-25, Volume: 467, Issue:1-3
Molecular and pharmacological characterization of the mouse histamine H3 receptor.
AID1346055Human H4 receptor (Histamine receptors)2001Molecular pharmacology, Mar, Volume: 59, Issue:3
Cloning, expression, and pharmacological characterization of a novel human histamine receptor.
AID1346017Rat H3 receptor (Histamine receptors)2000The Journal of pharmacology and experimental therapeutics, Jun, Volume: 293, Issue:3
Cloning of rat histamine H(3) receptor reveals distinct species pharmacological profiles.
AID1346107Human H3 receptor (Histamine receptors)2002European journal of pharmacology, Oct-18, Volume: 453, Issue:1
Characteristics of recombinantly expressed rat and human histamine H3 receptors.
AID1346107Human H3 receptor (Histamine receptors)2001The Biochemical journal, Apr-15, Volume: 355, Issue:Pt 2
Genomic organization and characterization of splice variants of the human histamine H3 receptor.
AID1346107Human H3 receptor (Histamine receptors)2000The Journal of pharmacology and experimental therapeutics, Jun, Volume: 293, Issue:3
Cloning of rat histamine H(3) receptor reveals distinct species pharmacological profiles.
AID1159607Screen for inhibitors of RMI FANCM (MM2) intereaction2016Journal of biomolecular screening, Jul, Volume: 21, Issue:6
A High-Throughput Screening Strategy to Identify Protein-Protein Interaction Inhibitors That Block the Fanconi Anemia DNA Repair Pathway.
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.
AID1798266H3R 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.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (276)

TimeframeStudies, This Drug (%)All Drugs %
pre-19900 (0.00)18.7374
1990's153 (55.43)18.2507
2000's91 (32.97)29.6817
2010's24 (8.70)24.3611
2020's8 (2.90)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 13.86

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 weak demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index13.86 (24.57)
Research Supply Index5.50 (2.92)
Research Growth Index4.18 (4.65)
Search Engine Demand Index10.37 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (13.86)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials3 (1.25%)5.53%
Trials0 (0.00%)5.53%
Reviews1 (0.42%)6.00%
Reviews1 (2.17%)6.00%
Case Studies0 (0.00%)4.05%
Case Studies0 (0.00%)4.05%
Observational0 (0.00%)0.25%
Observational0 (0.00%)0.25%
Other236 (98.33%)84.16%
Other45 (97.83%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]