Naluzotan(PRX 00023) is a novel and potent 5-HT1A agonist with IC50 and Ki values of approximately 20 nM and 5.1 nM, respectively.Naluzotan is a potent hERG K+ channel blocker with an IC50 value of 3800 nM.Naluzotan exhibits anxiolytic activity and can be used to study depression.

ERG K+ channel (human):3800 nM, 5-HT1A receptor:5.1 nM (Ki), 5-HT1A receptor:20 nM, Cell-based functional assay:20 nM (EC50), σ receptor:100 nM (Ki,guinea pig)

Naluzotan, with an EC50 of 20 nM, behaves as a full agonist in an in vitro cell-based functional assay. It exhibits significant affinity for the guinea pig sigma receptor (Ki = 100 nM) but does not inhibit cytochrome P450 isoforms (CYP) 1A2, 2C9, 2C19, 2D6, and 3A4[2].

In rats, when administered orally, Naluzotan shows 11% oral bioavailability with a serum half-life (t1/2) of 2−3.5 hours, reaching a Cmax level of 24 ± 13 ng/mL (3 mg/kg, oral). Naluzotan exhibits significant brain penetration, with a brain:serum concentration ratio of approximately 0.5 in rats at 1 hour following either intravenous or oral administration, and it achieves a brain concentration approximately equivalent to that of buspirone. In dogs, the pharmacokinetic profile of naluzotan demonstrates 16% oral bioavailability, a serum t1/2 of 1.1 hours when administered orally, and a Cmax level of 174 ± 141 ng/mL (3 mg/kg, oral)[1]. PRX-00023, at doses of 0.01-0.05 mg/kg administered intraperitoneally, significantly reduces ultrasonic vocalization (USV) rates in rats, but none of these doses induce sedation[1].