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.

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.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

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). PRX-00023 (0.01-0.05 mg/kg, i.p.) significantly reduces USV rates, but done of these doses produce sedation in rats.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

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). PRX-00023 (0.01-0.05 mg/kg, i.p.) significantly reduces USV rates, but done of these doses produce sedation in rats.

西域 has not independently confirmed the accuracy of these methods. They are for reference only.

• . Becker OM, et al. An integrated in silico 3D model-driven discovery of a novel, potent, and selective amidosulfonamide 5-HT1A agonist (PRX-00023) for the treatment of anxiety and depression. J Med Chem. 2006 Jun 1;49(11):3116-35.  [Content Brief]

  . Brunelli SA, et al. PRX-00023, a selective serotonin 1A receptor agonist, reduces ultrasonic vocalizations in infant rats bred for high infantile anxiety. Pharmacol Biochem Behav. 2009 Nov;94(1):8-15.  [Content Brief]