Zoniporide hydrochloride hydrate

Zoniporide (CP-597396) hydrochloride hydrate is a potent and selective inhibitor of sodium-hydrogen exchanger type 1 (NHE-1). Zoniporide hydrochloride hydrate inhibits human NHE-1 (IC50=14 nM), and has >150-fold selectivity versus other NHE isoforms. Zoniporide hydrochloride hydrate potently inhibits ex vivo NHE-1-dependent swelling of human platelets (IC50=59 nM)[1][2].

Signaling Pathways >> Membrane Transporter/Ion Channel >> Sodium Channel

Research Areas >> Cardiovascular Disease

IC50: 14 nM (NHE-1)[1]

Zoniporide hydrochloride hydrate (0.25-4 mg/kg; i.v.; every hour for 2 hours) elicits a dose-dependent reduction in infarct size (ED50=0.45 mg/kg/h) in open chest anesthetized rabbits[1]. Zoniporide exhibits moderate plasma protein binding, has a t1/2 of 1.5 hours in monkeys, and has one major active metabolite[1]. Zoniporide hydrochloride hydrate treatment shows the AUC0-∞ and t1/2 are 0.07 μg h/mL and 0.5 hours, respectively[2]. Animal Model: Rabbit[1] Dosage: 0.25, 1, 4 mg/kg Administration: Every hour for 2 hours; intravenous injection Result: Elicited a significant dose-dependent reduction in infarct size in the anesthetized rabbit. The ED50 was 0.45 mg/kg/h. Animal Model: Rat[2] Dosage: 1 mg/kg Administration: Intravenous injection(Pharmacokinetic Analysis) Result: The AUC0-∞ and t1/2 were 0.07 μg h/mL and 0.5 hours, respectively.

[1]. Tracey WR, et al. Zoniporide: a potent and selective inhibitor of the human sodium-hydrogen exchanger isoform 1 (NHE-1). Cardiovasc Drug Rev. 2003 Spring;21(1):17-32.

[2]. Guzman-Perez A, et al. Discovery of zoniporide: a potent and selective sodium-hydrogen exchanger type 1 (NHE-1) inhibitor with high aqueous solubility. Bioorg Med Chem Lett. 2001 Mar 26;11(6):803-7.