Background and Objective <p>Pulmonary arterial hypertension is a rare, progressive pulmonary vascular disease with limited therapeutic options. MN-08, a nitrate derivative of memantine, is under development for pulmonary arterial hypertension. The purpose of this study was to evaluate the safety, tolerability, and pharmacokinetics of MN-08 in healthy Chinese volunteers following single- and multiple-dose administration.</p> Methods <p>A phase I, single-center, randomized, double-blind, placebo-controlled study was conducted using dose-escalation designs for both single ascending doses (6–132 mg, <i>n</i> = 69) and multiple ascending doses (12–36 mg twice daily for 7 days, <i>n</i> = 30), and a crossover design for the food effect evaluation (24 mg, <i>n</i> = 18), with an 8-day wash-out interval between periods. Healthy Chinese volunteers aged 18–45 years were enrolled. Safety was monitored continuously from screening through to the end of the study, with adverse events recorded throughout. The study endpoints were the pharmacokinetic parameters of MN-08 following single-dose, multiple-dose, and high-fat/high-calorie breakfast administration. All pharmacokinetic parameters were performed using a non-compartmental analysis with Phoenix WinNonlin^® Version 8.2 (Certara USA, Inc., Princeton, NJ, USA).</p> Results <p>After a single dose of MN-08, the median time to maximum plasma concentration was 3.0–6.1 h and the mean half-life was 20.8–30.9 h. The mean maximum plasma concentration was 3.5–95.0 ng/mL. The mean area under the concentration–time curve (AUC) from the time of dosing to the last quantifiable concentration was 84–3428 h·ng/mL and the AUC from zero to infinity was 114–3618 h·ng/mL across all doses. In the multiple ascending dose study, the median time to maximum plasma concentration was 4.6–5.8 h and the half-life was 26.9–31.7 h. The mean maximum plasma concentration was 31.6–132.9 ng/mL. The mean AUC from the time of dosing to the last quantifiable concentration was 1291–5770 h·ng/mL and the AUC from zero to infinity was 1371–6237 h·ng/mL. Consumption of a high-fat and high-calorie meal had a minor effect on the peak concentration of MN-08. Drug accumulation was observed in the multiple ascending dose study and the mean accumulation index ranged from 3.76 to 4.33. There was no significant trend indicative of a sex effect. MN-08 was well tolerated in these healthy subjects. All adverse events were mild or moderate and no drug-related serious adverse events were reported.</p> Conclusions <p>MN-08 exhibited favorable pharmacokinetic characteristics and a good safety and tolerability profile in healthy Chinese subjects across the evaluated dose range. These findings support the progression of MN-08 to phase II studies for the treatment of pulmonary arterial hypertension in Chinese patients.</p> Clinical Trial Registration <p>ChiCTR.org.cn identifier number ChiCTR2000031414.</p>