Eplivanserin hemifumarate

Names

[ Name ]:
Eplivanserin hemifumarate

[Synonym ]:
Eplivanserin hemifumarate
(Z,E)-1-(2-Fluorophenyl)-3-(4-hydroxyphenyl)-2-propen-1-one O-[2-(dimethylamino)ethyl]oxime fumarate (2:1)
TRANS-2'-FLUORO-4-HYDROXYCHALCONE O-[(Z)-2-(DIMETHYLAMINO)ETHYL]OXIME--FUMARIC ACID (2:1)
SR-46349 hemifumarate salt

Biological Activity

[Description]:

Eplivanserin (SR-46349) hemifumarate is a potent, selective and orally active 5-HT2A receptor antagonist, with an IC50 of 5.8 nM in rat cortical membrane, and a Kd of 1.14 nM. Eplivanserin hemifumarate displays >20-fold selectivity more selective for 5-HT2A than 5-HT2B and 5-HT2C[1][2].

[Related Catalog]:

Research Areas >> Neurological Disease

Signaling Pathways >> GPCR/G Protein >> 5-HT Receptor

Signaling Pathways >> Neuronal Signaling >> 5-HT Receptor

[Target]

5-HT2A Receptor:5.8 nM (IC50)

5-HT2C Receptor:120 nM (IC50)

[In Vitro]

Eplivanserin hemifumarate (SR 46349B) shows weak inhibition on other 5-HT kinases, with IC50s of 0.12 μM (Pig cortex 5-HT1C), 14 μM (Rat hippocampus 5-HT1A), and 16 μM (Rat stnatum 5-HT1B, Ox caudate nucleus 5-HT1D). Eplivanserin also has inhibitory effects on rat cortex adrenergic α1 and α2, rat whole brain histammine H1, Na+ channel, and rat striatum dopamine D1 and D2, with IC50s of 3.4 μM, 1.0 μM, 5.0 μM, 39 μM, 9 μM and 28 μM, respectively[1].

[In Vivo]

Eplivanserin hemifumarate (SR 46349B) inhibits 5-HT2 receptor binding of [3H]ketanserin with an ED50 of 0.087 mg/kg after i.p. injection, and 0.097 mg/kg after p.o administration in mice[1]. SR 46349B (0.25-1 mg/kg; i.p.) blocks Cocaine-evoked hyperactivity following repeated Cocaine treatment in rats[2].

[References]

[1]. Rinaldi-Carmona M, et al. Biochemical and pharmacological properties of SR 46349B, a new potent and selective 5-hydroxytryptamine2 receptor antagonist. J Pharmacol Exp Ther. 1992 Aug;262(2):759-68.

[2]. Malgorzata Filip, et al. Contribution of serotonin (5-hydroxytryptamine; 5-HT) 5-HT2 receptor subtypes to the hyperlocomotor effects of cocaine: acute and chronic pharmacological analyses. J Pharmacol Exp Ther. 2004 Sep;310(3):1246-54.

Chemical & Physical Properties

[ Boiling Point ]:
456.3ºC at 760mmHg

[ Molecular Formula ]:
C₂₃H₂₅FN₂O₆

[ Molecular Weight ]:
444.45300

[ Flash Point ]:
229.8ºC

[ Exact Mass ]:
444.17000

[ PSA ]:
119.66000

[ LogP ]:
3.23880

[ Vapour Pressure ]:
1.63E-08mmHg at 25°C

MSDS

Click to get detail MSDS

Safety Information

[ Symbol ]:

GHS07, GHS09

[ Signal Word ]:
Warning

[ Hazard Statements ]:
H302-H410

[ Precautionary Statements ]:
P273-P501

[ RIDADR ]:
UN 3077 9 / PGIII

Articles

Nest building is impaired in the Ts65Dn mouse model of Down syndrome and rescued by blocking 5HT2a receptors.

Neurobiol. Learn. Mem. 116 , 162-71, (2014)

Down syndrome (DS) has an incidence of about 1/700 births, and is therefore the most common cause of cognitive and behavioral impairments in children. Recent studies on mouse models of DS indicate tha...

Role of serotonin (5-HT)2 receptors in cocaine self-administration and seeking behavior in rats.

Pharmacol. Rep. 57(1) , 35-46, (2005)

Previous studies have indicated a role of serotonin (5-HT)2 receptors in modulation of the behavioral effects of cocaine. In the present study, the efficacy of SR 46349B (a 5-HT(2A) receptor antagonis...

Activation of slowly conducting medullary raphe-spinal neurons, including serotonergic neurons, increases cutaneous sympathetic vasomotor discharge in rabbit.

Am. J. Physiol. Regul. Integr. Comp. Physiol. 288(4) , R909-18, (2005)

Neurons in the rostral medullary raphe/parapyramidal region regulate cutaneous sympathetic nerve discharge. Using focal electrical stimulation at different dorsoventral raphe/parapyramidal sites in an...