Thioperamide (maleate)

Names

[ Name ]:
Thioperamide (maleate)

[Synonym ]:
MR-12842 N-Cyclohexyl-4-(1H-imidazol-4-yl)-1-piperidinecarbothioamide maleate salt
1-Piperidinecarbothioamide, N-cyclohexyl-4-(1H-imidazol-5-yl)-, (2Z)-2-butenedioate (1:1)
MR-12842 (N-Cyclohexyl-4-(1H-imidazol-4-yl)-1-piperidinecarbothioamide maleate salt
Thioperamide Maleate
N-Cyclohexyl-4-(1H-imidazol-5-yl)-1-piperidinecarbothioamide (2Z)-2-butenedioate (1:1)
1-Piperidinecarbothioamide, N-cyclohexyl-4-(1H-imidazol-4-yl)-, (2Z)-2-butenedioate (1:1)
MFCD00083209
N-Cyclohexyl-4-(1H-imidazol-4-yl)piperidine-1-carbothioamide (2Z)-but-2-enedioate (1:1)

Biological Activity

[Description]:

Thioperamide maleate (MR-12842 maleate) is a potent, orally available, brain penetrant and selective H3 receptor antagonist with a Ki of 4.3 nM for inhibition of [3H]histamine release. Thioperamide maleate inhibits [3H]histamine synthesis with a Ki of 31 nM[1].

[Related Catalog]:

Signaling Pathways >> Immunology/Inflammation >> Histamine Receptor

Research Areas >> Neurological Disease

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

[Target]

H3 Receptor

[In Vitro]

Thioperamide inhibits [3H]-(R)α-MeHA binding rat brain and guinea-pig lung with Kis of 2.1 nM and 2.0 nM, respectively. Thioperamide competitively blocks H3-autoreceptors regulating [3H]histamine release with a mean apparent Ki of 4 nM[1]. Thioperamide (0.01-100 μM; 24 hours) promotes the viability of NE-4C stem cells in a concentration-dependent manner[2]. Thioperamide displays similar potencies at human H4 and H3 receptors (Ki=43 and 60 nM, respectively)[3]. Cell Viability Assay[2] Cell Line: NE-4C stem cells Concentration: 0.01, 0.1, 1, 10, 100 μM Incubation Time: 24 hours Result: The viability of NE-4C stem cells increased significantly to 150.83±6.91% when (1 μM) was administrated, and increased to 145.11±14.52% and 132.02%±25.65% when 10 μM and 100 μM were administrated respectively.

[In Vivo]

Thioperamide (5-20 mg/kg; i.p.) is able to facilitate reconsolidation of a contextually-conditioned fear memory in C57BL/6J mice[4]. Animal Model: Naive female C57BL/6J mice[4] Dosage: 5, 10 or 20 mg/kg Administration: Injections (i.p.) Result: Facilitated reconsolidation of a contextually-conditioned fear memory.

[References]

[1]. J M Arrang, et al. Highly Potent and Selective Ligands for Histamine H3-receptors. Nature. 1987 May 14-20;327(6118):117-23.

[2]. Na Wang, et al. Histamine H3 Receptor Antagonist Enhances Neurogenesis and Improves Chronic Cerebral Hypoperfusion-Induced Cognitive Impairments. Front Pharmacol. 2020 Jan 21;10:1583.

[3]. Y Charlier, et al. Differential Effects of Histamine H(3) Receptor Inverse Agonist Thioperamide, Given Alone or in Combination With the N-methyl-d-aspartate Receptor Antagonist Dizocilpine, on Reconsolidation and Consolidation of a Contextual Fear Memory in Mice. Neuroscience. 2011 Oct 13;193:132-42.

[4]. Gbahou F, et al. Compared pharmacology of human histamine H3 and H4 receptors: structure-activity relationships of histamine derivatives. Br J Pharmacol. 2006;147(7):744-754.

Chemical & Physical Properties

[ Molecular Formula ]:
C₁₉H₂₈N₄O₄S

[ Molecular Weight ]:
408.515

[ Exact Mass ]:
408.183136

[ PSA ]:
150.64000

[ LogP ]:
2.83690

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

[ Risk Phrases ]:
R36/37/38

[ Safety Phrases ]:
S26

[ 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...

Effect of thioperamide, a histamine H3 receptor antagonist, on electrically induced convulsions in mice.

Eur. J. Pharmacol. 234(1) , 129-33, (1993)

The effect of thioperamide, a histamine H3 receptor antagonist, on electrically induced convulsions was studied in mice. Thioperamide significantly and dose dependently decreased the duration of each ...