**Background:** The novel tryptamine hallucinogen 5-methoxy-N-methyl-N-isopropyltryptamine (5-MeO-MiPT, known as "Moxy") is a new psychoactive substance (NPS) first identified in Italy in 2014. Despite its known hallucinogenic effects, limited information exists on its pharmaco-toxicological profile. Following a seizure by Italian law enforcement and a human intoxication case, this study aimed to characterize the acute in vivo effects of 5-MeO-MiPT on sensorimotor responses, thermoregulation, motor activity, sensory gating, and cardiorespiratory parameters in mice, alongside in silico ADMET prediction.
**Methods:** A total of 110 adult male CD-1 mice were used. For safety pharmacology studies (visual, acoustic, tactile responses; core and surface temperature; accelerod and drag tests), eight mice per treatment group (vehicle or 0.01, 0.1, 1, 10, 30 mg/kg i.p.) were employed. For prepulse inhibition (PPI), eight mice per group (vehicle or 0.01, 0.1, 1, 10 mg/kg i.p.) were used. Cardiorespiratory parameters (heart rate, breath rate, SpO2, pulse distension) were monitored in six mice per group (vehicle or 30 mg/kg i.p.) using MouseOx Plus. Blood pressure (systolic and diastolic) was measured in five mice per group (vehicle or 30 mg/kg i.p.) via tail-cuff plethysmography (BP-2000). Behavioral tests were conducted over 5 hours post-injection. In silico ADMET prediction was performed using ADMET Predictor® version 10.4 for 5-MeO-MiPT, 5-MeO-DIPT, and DMT.
**Key Results:** 5-MeO-MiPT dose-dependently reduced visual object response (at 1 mg/kg ~33% reduction; at 10 and 30 mg/kg ~55% reduction at 10 min) and visual placing response (30 mg/kg impaired ~80% at 5 min, persisting up to 180 min). High doses (10-30 mg/kg) enhanced tactile responses during the first 60 min, while acoustic responses were not significantly affected. Core temperature decreased only at 30 mg/kg (hypothermic effect at 35 min). Motor coordination was impaired at 30 mg/kg: accelerod test showed ~70% reduction at 40 min, drag test ~60% reduction at 45 min, persisting up to 135 min. PPI was impaired at 1 mg/kg (at 68 dB at 15 min, p=0.0002; at 85 dB at 120 min, p=0.0005) and at 10 mg/kg (at all prepulse intensities at 15 and 120 min, p<0.01). Cardiorespiratory effects at 30 mg/kg included a triphasic heart rate response (initial increase, then bradycardia 40-20% below basal for ~2.5 h, then tachycardia ~20% above basal at 330 min), tachypnea (max ~150% at 155 min), decreased pulse distension, and mild SpO2 increase. Blood pressure showed an initial decrease (systolic ~80 mmHg, diastolic ~40 mmHg) followed by an increase. In silico ADMET predicted high permeability, high BBB penetration (99%), no hepatotoxicity risk, but cytochrome risk for 5-MeO-MiPT (CYP1A2 and CYP2C9 high clearance) and potential CYP2D6 inhibition.
**Clinical Implications:** The human intoxication case (23-year-old male) presented with tachycardia (107 bpm), catatonia, drowsiness, and muteness, with blood pressure 150/90 mmHg, matching the preclinical findings. The study demonstrates that 5-MeO-MiPT can impair sensorimotor function, motor coordination, and cardiorespiratory stability, particularly at high doses. These effects may compromise daily activities and driving safety. However, the compound's therapeutic potential in psychiatric disorders (e.g., depression, anxiety) should not be excluded, as the most severe effects occurred at doses exceeding common human use. The in silico ADMET profile suggests a low hepatotoxicity risk but highlights potential drug-drug interactions via CYP2D6 inhibition.