Naluzotan

Naluzotan is a novel, potent, and selective amidosulfonamide 5-HT1A agonist with IC₅₀ and K_i of appr 20 nM and 5.1 nM, used for the treatment of anxiety and depression; Also a weak hERG K⁺ channel blocker, with IC₅₀ of 3800 nM. IC50 & Target: IC50: appr 20 nM (5-HT1A)^[2], 3800 nM (hERG K⁺ channel)^[1]
Ki: 5.1 nM (5-HT1A)^[1] In Vitro: Naluzotan behaves as a full agonist in an in vitro cell-based functional assay with an EC₅₀ of 20 nM. Naluzotan has significant affinity is the guinea pig sigma receptor (K_i = 100 nM), but does not inhibit cytochrome P450 isoforms (CYP) 1A2, 2C9, 2C19, 2D6, and 3A4^[1]. In Vivo: In rats Naluzotan shows 11% oral bioavailability with a serum t_1/2 of 2?3.5 h when administrated po, attaining a C_max level of 24 ± 13 ng/mL (3 mg/kg, po). Naluzotan shows significant brain penetration, achieving a brain:serum concentration ratio of approximately 0.5 in the rat at 1 h following either intravenous or oral administration and reaching brain concentration approximately equivalent to that of buspirone. In dogs the pharmacokinetic profile of naluzotan shows 16% oral bioavailability, a serum t_1/2 of 1.1 h po, and a C_max level of 174 ± 141 ng/mL (3 mg/kg, po)^[1]. PRX-00023 (0.01-0.05 mg/kg, i.p.) significantly reduces USV rates, but done of these doses produce sedation in rats^[2].