(R)-(-)-α-Methylhistamine dihydrochloride

Names

[ Name ]:
(R)-(-)-α-Methylhistamine dihydrochloride

[Synonym ]:
R(-)-α-Methylhistamine Dihydrochloride

Biological Activity

[Description]:

(R)-(-)-α-Methylhistamine dihydrochloride is a potent, selective and brain-penetrant agonist of H3 histamine receptor, with a Kd of 50.3 nM[1][2]. (R)-(-)-α-Methylhistamine dihydrochloride can enhance memory retention, attenuates memory impairment in rats[3][4][5].

[Related Catalog]:

Signaling Pathways >> Immunology/Inflammation >> Histamine Receptor

Research Areas >> Neurological Disease

Signaling Pathways >> GPCR/G Protein >> Histamine Receptor

[Target]

H3 Receptor:50.3 nM (Kd)

[In Vitro]

(R)-(-)-α-Methylhistamine dihydrochloride is an H3-agonist that is >10 times as potent as histamine (HA). Its selectivity toward H3-receptors is >1000 times as high as that of HA. (R)-(-)-α-Methylhistamine dihydrochloride has only weak affinities for H1 and H2 receptor with a pKi=4.8 and <3.5, repectively. (R)-(-)-α-Methylhistamine dihydrochloride displays >200-fold selectivity over H4 receptors[1][2][3].

[In Vivo]

Pretreatment with (R)-(-)-α-Methylhistamine dihydrochloride (RAMH; 10 mg/kg; i.p.; 60 min before training) reverses Propofol‐induced (25 mg/kg; i.p.; 30 min before training) memory retention[5]. (R)-(-)-α-Methylhistamine dihydrochloride (6.3 mg/kg; i.p.) significantly decreases the steady-state t-MH level in the mouse brain, whereas these compounds produced no significant changes in the HA level[3]. Animal Model: Male Sprague‐Dawley rats (10-12 week)[3] Dosage: 10 mg/kg Administration: IP; 60 min before training Result: Reversed propofol‐induced memory retention.

[References]

[1]. Arrang JM, et al. Highly potent and selective ligands for histamine H3-receptors. Nature. 1987 May 14-20;327(6118):117-23.

[2]. Mohammad Shahid, et al. Histamine, Histamine Receptors, and their Role in Immunomodulation: An Updated Systematic Review. The Open Immunology Journal, 2009, 2, 9-41.

[3]. Oishi R, et al. Effects of the histamine H3-agonist (R)-alpha-methylhistamine and the antagonist thioperamideon histamine metabolism in the mouse and rat brain. J Neurochem. 1989 May;52(5):1388-92.

[4]. Yamasaki S, et al. The disposition of (R)-alpha-methylhistamine, a histamine H3-receptor agonist, in rats. J Pharm Pharmacol. 1994 May;46(5):371-4.

[5]. Li WW, et al. (R)-alpha-methylhistamine suppresses inhibitory neurotransmission in hippocampal CA1 pyramidal neurons counteracting propofol-induced amnesia in rats. CNS Neurosci Ther. 2014 Sep;20(9):851-9.

Chemical & Physical Properties

[ Molecular Formula ]:
C₆H₁₃Cl₂N₃

[ Molecular Weight ]:
198.09400

[ Exact Mass ]:
197.04900

[ PSA ]:
54.70000

[ LogP ]:
2.77620

MSDS

Click to get detail MSDS

Safety Information

[ Symbol ]:

GHS07

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H315-H319-H335

[ Precautionary Statements ]:
P261-P305 + P351 + P338

[ Personal Protective Equipment ]:
dust mask type N95 (US);Eyeshields;Gloves

[ Hazard Codes ]:
Xi: Irritant;

[ Risk Phrases ]:
36/37/38

[ Safety Phrases ]:
26-36

[ RIDADR ]:
NONH for all modes of transport

Articles

Highly potent and selective ligands for histamine H3-receptors.

Nature 327 , 117, (1987)

New drugs selective for histamine H3-receptors can be used to establish that these receptors are involved in the feedback control of histamine synthesis and release, and to demonstrate their distribut...

Effects of the histamine H3-agonist (R)-alpha-methylhistamine and the antagonist thioperamide on histamine metabolism in the mouse and rat brain.

J. Neurochem. 52 , 1388, (1989)

To study the feedback control by histamine (HA) H3-receptors on the synthesis and release of HA at nerve endings in the brain, the effects of a potent and selective H3-agonist, (R)-alpha-methylhistami...

Structure-activity relations of histamine analogs. XX. Absolute configuration and histamine-like activity of enantiomeric α-methyl histamines. Gerhard, et al.

Arch. Pharm. Res. 313 , 709, (1980)

Related Compounds

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