The management of Parkinson’s disease (PD) is frequently compromised by complications induced by dopaminergic treatment such as involuntary movements (dyskinesias) and psychosis. Mesdopetam (IRL790) is a novel dopamine D3 receptor antagonist developed for the management of complications of therapy in PD. Aim To evaluate safety, tolerability and pharmacokinetics of escalating single and multiple doses of mesdopetam Method We conducted a prospective, single-centre, randomized, double-blind, placebo-controlled phase I, first in human (FIH) study with mesdopetam administered to healthy male subjects. Results Overall, mesdopetam was well tolerated up to 120 mg single dose and up to 80 mg upon multiple dosing. AEs were mainly related to the nervous system and were dose dependent. No SAEs occurred and no AEs led to withdrawal. The results of the SAD and the MAD parts indicated dose- and time-independent pharmacokinetics with rapid absorption, maximum plasma levels generally reached within 2 hours after dosing. The average terminal half-life of mesdopetam ranged from 6.4 to 7.1 hours in the SAD part, and 6.3 to 7.3 hours in the MAD part. No accumulation was observed upon multiple dosing. Safety findings were unremarkable with no changes demonstrated in vital signs, ECG parameters or physical examination. Mesdopetam produced a dose-dependent increase in plasma prolactin, compatible with target engagement. Conclusion Mesdopetam was safe and well tolerated in healthy male volunteers. Pharmacokinetic analysis indicated rapid absorption and dose-linear pharmacokinetics of mesdopetam, with a plasma half-life around 7 hours, upon single and repeated dosing. The pharmacokinetics of mesdopetam supports twice daily use in patients.