Naluzotan hydrochloride (PRX 00023 hydrochloride) is a hERG K+ channel blocker with an IC50 value of 3800 nM and is commonly used in the study of anxiety and depression.Naluzotan hydrochloride is also a novel, potent, and selective 5-HT1A agonist, with an IC50 value of about 20 nM and a Ki value of about 5.1 Naluzotan hydrochloride is also a novel, potent and selective 5-HT1A agonist with an IC50 of approximately 20 nM and a Ki of approximately 5.1 nM.

5-HT1A:20 nM, 5-HT1A:5.1 nM, ERG K+ (human):3800 nM

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

In rats Naluzotan hydrochloride shows 11% oral bioavailability with a serum t1/2 of 2−3.5 h when administrated po, attaining a Cmax level of 24 ± 13 ng/mL (3 mg/kg, po). Naluzotan hydrochloride 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 hydrochloride shows 16% oral bioavailability, a serum t1/2 of 1.1 h po, and a Cmax 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]