PRX-07034 hydrochloride is a selective antagonist of 5-HT6 receptor. It has cognition and memory-enhancing properties and potently decreases food intake and body weight in rodents. PRX-07034 hydrochloride is both a potent (Ki = 4-8 nM) and highly selective 5-HT(6) receptor antagonist (≥100-fold selectivity for the 5-HT(6) receptor compared to 68 other GPCRs, ion channels, and transporters, except D(3) (Ki = 71 nM) and 5-HT(1B) (Ki = 260 nM) receptors.

5-HT1B receptor:260 nM (Ki), 5-HT1A receptor:420 nM (Ki), 5-HT2B receptor:2.5 μM (IC50), 5-HT6 receptor:19 nM (IC50), 5-HT6 receptor:4-8 nM (Ki), μ opioid receptor:0.45 μM (Ki), D3 receptor:71 nM (Ki), H2 receptor:0.64 μM (Ki), 5-HT2C receptor:3.7 μM (IC50), 5-HT2A receptor:2.5 μM (IC50), 5-HT1D receptor:2.8 μM (Ki)

PRX-07034 is a potent (Ki = 4-8 nM) and highly selective 5-HT(6) receptor antagonist with 100-fold selectivity over 68 other GPCRs, ion channels, and transporters, except for D(3) (Ki = 71 nM) and 5-HT(1B) (Ki = 260 nM) receptors. It demonstrated antagonist activity in cyclic AMP quantification (IC(50) = 19 nM) without affecting basal levels and showed no agonist activity up to 10 μM. At doses of 1 and 3 mg/kg, PRX-07034 significantly enhanced delayed spontaneous alternation and switching between place and response strategies, but did not affect initial learning of place or response discrimination.