The drug 2-fluorodeschloroketamine (2-FDCK), a ketamine substitute used by drug abusers, shows abuse potential comparable to ketamine. In mice, 2-FDCK at 3 mg/kg induced conditioned place preference, similar to ketamine. Acute injections at 30 mg/kg increased locomotor activity, and repeated treatments led to locomotor sensitization after withdrawal. 2-FDCK supported self-administration at 0.5 mg/kg/infusion, matching ketamine, with peak seeking at 1 mg/kg. In drug discrimination tests, 2-FDCK dose-dependently substituted for ketamine with comparable potency. These findings indicate that 2-FDCK has an abuse potential similar to ketamine.
A first-in-human Phase 0 intratarget microdosing study shows that delivering a tiny dose of a new inflammasome inhibitor directly into the lungs of patients with interstitial lung disease is feasible. A 100 microgram microdose of ADS032, a dual NLRP1/NLRP3 inhibitor, was administered to distal airways via bronchoscopy. The drug was detected in plasma, bronchoalveolar lavage fluid, distal airway micro-aspirates, and recovered cells without cross-contamination. Fluorescent labeling allowed direct visualization of alveolar drug uptake in ex vivo human lung tissue. This intrapulmonary microdosing approach offers a human-relevant platform for early pharmacological evaluation of lung therapeutics before Phase 1 trials.