ARN19702 is a selective, orally active, reversible, and brain-penetrant N-acylethanolamine acid amidase (NAAA) inhibitor with an IC50 of 230 nM for human NAAA, exhibiting a broad analgesic profile [1] [2].

NAAA:230 nM

ARN19702, administered orally (po) at dosages of 3-10 mg/kg daily for seven consecutive days, effectively reduces Paclitaxel-induced neuropathic nociception in male rats without causing subacute antinociceptive tolerance [1]. In male mice, ARN19702 demonstrates a dose-dependent reduction in spontaneous nocifensive behaviors triggered by intraplantar formalin, and alleviates hypersensitivity following intraplantar carrageenan injection, paw incision, or sciatic nerve ligation, at dosages ranging from 0.1-30 mg/kg (po) [1]. Additionally, at a dosage range of 3-10 mg/kg (po), ARN19702 offers significant protection against multiple sclerosis in mice [2]. Pharmacokinetic analysis in mice reveals that at a 3 mg/kg dosage, ARN19702 achieves a maximum concentration (Cmax) of 1660±166 ng/mL and 613±68 ng/mL for intravenous (i.v.) and oral administration respectively, with corresponding times to reach Cmax (Tmax) of approximately 5.0 minutes (i.v.) and 30 minutes (po). The clearance (CL) rates stand at 33.2±1.6 mL/min/kg (i.v.) and 49±8 mL/min/kg (po), with half-lives (t 1/2) of 73.9±3.7 minutes (i.v.) and 104±16 minutes (po). Area under the curve (AUC) measurements indicate plasma levels of 1366.8±68.3 h×ng/mL (i.v.) and 988±157 h×ng/mL (po), and brain levels of 404.3±109.1 h×ng/mL (i.v.) and 181±28 h×ng/mL (po), with an oral bioavailability (F) of 72±11%.