Immethridine
Immethridine is a selective histamine H3 receptor agonist. Immethridine inhibits the expression of TLR4/CD14 and the phosphorylation of NF-κB p65. Immethridine reduces inverse agonist-induced scratching, induces cheek-directed wiping rather than itching, and exerts a protective effect against HCl-induced gastric mucosal injury without affecting gastric acid secretion. Immethridine attenuates experimental autoimmune encephalomyelitis and reduces inflammatory infiltration/demyelination in the spinal cord. Immethridine can be used in research on autism spectrum disorders.
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- CAS No.: 87976-03-2
- Formule: C9H9N3
- Masse moléculaire:159.19
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Stockage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Activité biologique
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Chemical Information
- Protocole
- Pureté et documentation
- Références
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Activité biologique
Description
IC50 & Target
[1]|
H3 receptor |
TLR4 |
Cellular Effect
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Cell Line
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Type | Value | Description | References |
|---|---|---|---|---|
| CHO | EC50 |
1.1 nM
Compound: 5
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Agonist activity at human histamine H3 receptor expressed in CHO cells assessed as [35S]GTPgammaS binding
Agonist activity at human histamine H3 receptor expressed in CHO cells assessed as [35S]GTPgammaS binding
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[PMID: 20690643] |
In Vitro
Immethridine (100 μM) depolarizes the membrane potential of masseter motor neurons in rat brainstem slices by 6.6 mV without affecting input resistance[3].
Immethridine (0.01 nM-0.1 mM; 60 min) is a selective rat histamine H3 receptor agonist (pKi 7.97) with 75-fold selectivity for rat H4 in radioligand binding assays using HEK293T membranes[4].
Immethridine shows high affinity for the histamine H3 receptor in SK-N-MC membrane binding data (pKi 9.07), with 288-fold selectivity over H4[4].
Immethridine acts as a full agonist at the human histamine H3 receptor in SK-N-MC cells with a pEC50 of 9.74, and has a pEC50 of 6.04 at the human H4 receptor[5].
Immethridine inhibits electrically induced twitch contractions of the guinea pig ileum myenteric plexus, with a pD2 of 7.45 and an Emax of 38.5%[5].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
In Vivo
Immethridine (30 mg/kg; intraperitoneal injection; single dose; 30 min before intradermal injection of Pitolisant) reduces Pitolisant (HY-12199)-induced acute itch scratching behavior in female BALB/c mice[8].
Immethridine (20-45 mg/kg; intraperitoneal injection) reduces spontaneous activity in C57BL/6J mice and, at 45 mg/kg, increases the time spent in stereotyped patterns while decreasing grooming behavior[10].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 (female, 8-10 weeks old)[1]
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Dosage:15 mg/kg
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Administration:i.p.; every other day; after observable signs of EAE occurred
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Result:Immethridine-administered EAE mice had lower disease scores than control EAE mice.
At day 21, spinal cord sections from Immethridine-administered EAE mice showed fewer inflammatory infiltrates by H&E staining and decreased demyelination by LFB staining.
Splenocytes from Immethridine-administered EAE mice showed lower levels of TNF-α, IFN-γ, and IL-17A.
In splenocytes from Immethridine-administered EAE mice, Th1 cells were 4.6% of CD4+ cells versus 7.0% in vehicle-administered EAE mice, and Th17 cells were 6.7% versus 9.2%, respectively.
MOG35-55-specific T cell proliferation was lower in Immethridine-administered EAE mice.
Expression of CD40 and CD86 on DCs was lower in splenocytes from Immethridine-administered EAE mice.
MHCII expression on DCs in spinal cord was down-regulated in Immethridine-administered EAE mice.
There were fewer Th1 and Th17 cells in spinal cord from Immethridine-administered EAE mice.
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Animal Model:Wistar (male; 180-200 g)[4]
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Dosage:30 mg/kg
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Administration:s.c.; single dose; 30 min before intragastric HCl
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Result:In conscious rats, immethridine and methimepip significantly reduced (66% and 48% inhibition, respectively) the gastric lesions induced by HCl; the effect of immethridine was antagonized by the H3 receptor antagonist A-331440, but not by the H4 receptor antagonist JNJ7777120.
Previous administration of immethridine and methimepip (both at 30 mg/kg) caused a significant inhibition of the mucosal damage induced by concentrated acid.
The inhibitory effect of immethridine was prevented by prior administration of the histamine H3 receptor antagonist A-331440 (30 mg/kg), but not by the selective histamine H4 receptor antagonist JNJ7777120 (10 mg/kg).
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Animal Model:BALB/c (female, 6-8 weeks old)[8]
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Dosage:30 mg/kg
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Administration:i.p.; single administration; 30 min before intradermal pitolisant
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Result:In mice administered immethridine (30 mg/kg i.p.), intradermal pitolisant-induced scratching was 13 bouts/1 h.
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Animal Model:C57BL/6J (male; 11 weeks of age at start; JAX stock #000664)[10]
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Dosage:20 mg/kg and 45 mg/kg
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Administration:i.p.; 30 min before behavioral testing; acute; one-week wash-out periods between assessments
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Result:Decreased distance moved in C57BL/6J mice, with reductions in locomotor activity at 20 mg/kg and 45 mg/kg.
At 45 mg/kg, the reduction in locomotor activity was associated with increased time spent in stereotypic patterns and reduced grooming behavior.
The increased stereotypic patterns at high-dose immethridine occurred in mice with very low activity levels, consistent with general sedative properties.
Chemical Information
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CAS No. 87976-03-2
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Masse moléculaire 159.19
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Formule C9H9N3
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SMILES
C1(CC2=CN=CN2)=CC=NC=C1
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Livraison
Room temperature in continental US; may vary elsewhere.
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Stockage
Please store the product under the recommended conditions in the Certificate of Analysis.
Pureté et documentation
Références
[1]. Shi Y, et al. Immethridine, histamine H-receptor (HR) agonist, alleviated experimental autoimmune encephalomyelitis via inhibiting the function of dendritic cells. Oncotarget. 2017 Sep 26;8(43):75038-75049. [Content Brief]
[4]. Coruzzi G, et al. Selective histamine H₃ and H₄ receptor agonists exert opposite effects against the gastric lesions induced by HCl in the rat stomach. European journal of pharmacology. 2011 Nov 01;669(1-3):121-7. [Content Brief]
[5]. Kitbunnadaj R, et al. Identification of 4-(1H-imidazol-4(5)-ylmethyl)pyridine (immethridine) as a novel, potent, and highly selective histamine H(3) receptor agonist. Journal of medicinal chemistry. 2004 May 06;47(10):2414-7. [Content Brief]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Immethridine Related Classifications
HY-108058 Related Classifications
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