Parkinson's disease psychosis (PDP) is a common and distressing complication of Parkinson's disease (PD), characterized by hallucinations and delusions. This research aimed to assess the pharmacokinetics and safety of NH130, a selective serotonin 5-HT2A inverse agonist, as a potential PDP treatment in healthy individuals.We conducted clinical pharmacokinetic studies and safety evaluations for NH130, employing a physiologically based pharmacokinetic (PBPK) model to predict its behavior in human body.In a single-dose escalation study, healthy volunteers received NH130 at varying doses (2 mg, 6 mg, 12 mg, 24 mg, 40 mg, 60 mg, and 90 mg) or a placebo. The drug demonstrated favorable pharmacokinetics, with no serious adverse events (AEs) reported. Clinical plasma concentrations correlated well with PBPK model predictions, validating the model's utility for guiding future clinical development.NH130 showed promising pharmacokinetic characteristics and safety profile, supporting its progression to multi-dose trials and suggesting its potential as a therapeutic agent for PDP.http://www.chinadrugtrials.org.cn/index.html, Identifier CTR20230409.Copyright © 2024 Zhang, Zhao, Du and Zhang.