Eplivanserin (hemifumarate)

Eplivanserin (SR-46349) hemifumarate is a potent, selective and orally active 5-HT_2A receptor antagonist, with an IC₅₀ of 5.8 nM in rat cortical membrane, and a K_d of 1.14 nM. Eplivanserin hemifumarate displays >20-fold selectivity more selective for 5-HT_2A than 5-HT_2B and 5-HT_2C^[1][2]. In Vitro: Eplivanserin hemifumarate (SR 46349B) shows weak inhibition on other 5-HT kinases, with IC₅₀s of 0.12 μM (Pig cortex 5-HT_1C), 14 μM (Rat hippocampus 5-HT_1A), and 16 μM (Rat stnatum 5-HT_1B, Ox caudate nucleus 5-HT_1D). 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].