PF-04995274

PF-04995274 is a potent, high-affinity, orally active and partial serotonin 4 receptor (5-HT₄R) agonist. PF-04995274 has an EC₅₀ range of 0.26-0.47 nM for human 5-HT_4A/4B/4D/4E (K_i range of 0.15-0.46 nM), and has an EC₅₀ range of 0.59-0.65 nM for rat 5-HT_4S/4L/4E (K_i of 0.30 nM for rat 5-HT_4S). PF-04995274 is brain penetrant and can be used for cognitive disorders associated with Alzheimer's disease^[1][2][3]. IC50 & Target: 5-HT₄ receptor^[1][2][3] In Vitro: PF-04995274 has EC₅₀ values of 0.47 nM, 0.36 nM, 0.37 nM, 0.26 nM, 0.59 nM, 0.65 nM and 0.62 nM for human 5-HT_4A/4B/4D/4E and rat 5-HT_4S/4L/4E, respectively. PF-04995274 has K_i values of 0.36 nM, 0.46 nM, 0.15 nM, 0.32 nM and 0.3nM for human 5-HT_4A/4B/4D/4E and rat 5-HT_4S, respectively^[3]. In Vivo: PF-04995274 (3-10 mg/kg; intravenous injection; for 17 days; male 129S6/SvEv mice) treatment results in prophylactic efficacy by attenuating learned fear and decreasing stress-induced depressive-like behavior^[1].