Xaliproden free base  (Synonyms: SR57746A free base)

Xaliproden (SR57746) free base is an orally active, highly selective 5-HT1A receptor agonist. Xaliproden free base activates pertussis toxin-sensitive G protein-coupled signaling cascades, as well as the PKC, ERK1/ERK2, Akt and p21 Ras/MEK-1 pathways. Xaliproden free base also downregulates the JNK/p66/c-Jun signaling pathway, induces phosphorylation of the shc adaptor protein, regulates extracellular dopamine and 5-HT levels, and induces [³⁵S]GTPγS labeling in rat brain structures rich in 5-HT1A receptors. Xaliproden free base exerts neurotrophic, neuroprotective, renoprotective, anti-inflammatory, anti-apoptotic, anti-fibrotic and analgesic effects. Xaliproden free base also enhances NGF-induced neurite outgrowth, promotes motor neuron survival, attenuates renal tubular injury and inhibits chemotherapy-induced mechanical allodynia, without activating or altering NGF-induced TrkA receptor activation. Xaliproden free base can be used in the research of motor neuron disease, diabetic nephropathy, chemotherapy-induced peripheral neuropathy, amyotrophic lateral sclerosis, Alzheimer's disease, acute tonic nociceptive pain, inflammatory pain, depression and anxiety^[1][2][3][4].

Xaliproden free base (1-10 μM; 5-30 min) does not activate the TrkA receptor in rat pheochromocytoma PC12 cells^[1].
Xaliproden free base (1 μM; 5 min-48 h) induces time-dependent tyrosine phosphorylation of the p66^shc and p52^shc isoforms in rat pheochromocytoma PC12 cells, with the phosphorylation of p66^shc peaking at 5 min and that of p52^shc peaking at 48 h^[1].
Xaliproden free base (0.1-5 μM; 5-30 min) induces dose-dependent transient activation of ERK1/ERK2 MAP kinases in PC12 rat pheochromocytoma cells, with a 3-fold activation peak of ERK2 at 1 μM for 5 min, and the maximum activation level achieved at 5 μM for 5 min^[1].
Activation of ERK1/ERK2 MAP kinases and phosphorylation of PKC isoforms induced by xaliproden hydrochloride (1 μM; 5-30 min) in PC12 rat pheochromocytoma cells depend on PKC activity, whereas 5-HT_1A receptor antagonism or G_i/o protein inactivation inhibits PKC activation^[1].
Xaliproden free base (1-10 μM; 24 h) protects human renal proximal tubular epithelial cells from high glucose-induced injury by inhibiting the JNK/p65/c-Jun signaling pathway and alleviating inflammation, apoptosis and fibrosis^[2].
Xaliproden free base (10 μM) activates G proteins via native 5-HT_1a receptors in the rat hippocampus, lateral septum, frontal cortex and entorhinal cortex, and this effect is completely blocked by the 5-HT_1a receptor antagonist WAY100635 (HY-10349)^[4].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Xaliproden free base extends the average survival time and improves motor function in pmn mice with hereditary axonopathy, and rescues motor neurons from death in mice with transected sciatic nerves^[1].
Xaliproden (0.3-1.5 mg/kg/day; oral administration; once daily; for 4 consecutive weeks) free base exerts renoprotective effects on db/db mice with diabetic nephropathy by significantly improving renal function, reducing proteinuria, alleviating renal tubular injury and fibrosis, as well as blocking inflammatory, apoptotic and fibrotic pathways via inhibition of the JNK/p65/c-Jun signaling axis^[2].
Xaliproden (0.3-3 mg/kg; p.o.; single administration) free base significantly, persistently and dose-dependently inhibits Paclitaxel (HY-B0015)-induced mechanical allodynia^[3].
Xaliproden (0.3-3 mg/kg; p.o.; single administration) free base exerts only a mild, transient 19% inhibition of vincristine (HY-N0488A)-induced mechanical allodynia at the single dose of 3 mg/kg, shows no effect at low doses, and does not alter the tibial nerve firing response in vincristine-treated mice^[3].
Xaliproden (0.63-40 mg/kg; p.o.; single administration) free base produces a dose-dependent inhibitory effect on in vivo 5-HT_1A receptor binding in the frontal cortex and hippocampus of mice, with ID₅₀ values of 3.5 mg/kg and 3.3 mg/kg (p.o.), respectively^[4].
Xaliproden (0.63-10 mg/kg; intraperitoneal injection; single administration) free base dose-dependently increases dopamine levels in the prefrontal cortex of rats (ED₅₀=0.7 mg/kg, i.p.) and decreases 5-HT levels in the rat hippocampus (ED₅₀=1.2 mg/kg, i.p.) via activation of the 5-HT_1A receptor^[4].
Xaliproden (0.63-10 mg/kg; intraperitoneal injection; single administration) free base exerts a dose-dependent, 5-HT_1A receptor-mediated antinociceptive effect in the rat formalin pain test, and completely inhibits paw licking and lifting responses at 10 mg/kg (i.p.)^[4].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

381.43

C₂₄H₂₂F₃N

135354-02-8

FC(F)(F)C1=CC(C2=CCN(CC2)CCC3=CC=C4C=CC=CC4=C3)=CC=C1

Room temperature in continental US; may vary elsewhere.

Please store the product under the recommended conditions in the Certificate of Analysis.

• [1]. Appert-Collin A, et al. Xaliproden (SR57746A) induces 5-HT1A receptor-mediated MAP kinase activation in PC12 cells. Int J Immunopathol Pharmacol. 2005;18(2):233-244.

  [2]. Lee HJ, et al. Xaliproden improves diabetic kidney disease through JNK-mediated renal tubular protection. Biochem Pharmacol. Published online March 22, 2026.

  [3]. Andoh T, et al. Effects of xaliproden, a 5-HT₁A agonist, on mechanical allodynia caused by chemotherapeutic agents in mice. Eur J Pharmacol. 2013;721(1-3):231-236.  [Content Brief]

  [4]. Martel JC, et al. 5-HT1A receptors are involved in the effects of xaliproden on G-protein activation, neurotransmitter release and nociception. Br J Pharmacol. 2009;158(1):232-242.