Proof-of-Concept for the Analgesic Effect and Thermoregulatory Safety of Orally Administered Multi-Target Compound SZV 1287 in Mice: A Novel Drug Candidate for Neuropathic Pain

SZV 1287 (3-(4,5-diphenyl-1,3-oxazol-2-yl)propanal oxime) is a novel multi-target candidate under preclinical development for neuropathic pain. It inhibits amine oxidase copper containing 3, transient receptor potential ankyrin 1 and vanilloid (TRPV1) receptors. Mainly acidic conditions, it transformed to the cyclooxygenase inhibitor oxaprozin, which ineffective neuropathy. Therefore, an enterosolvent capsule suggested oral formulation, we investigated nociception, basic kinetics, thermoregulatory safety in mice. The antihyperalgesic effect of (10, 20, 50, 200 mg/kg, p.o.) was determined partial sciatic nerve ligation-induced traumatic neuropathy by aesthesiometry, brain plasma concentrations HPLC, deep body temperature thermometry. Its on proton-induced TRPV1 activation involved thermoregulation assessed microfluorimetry cultured trigeminal neurons. three higher doses significantly, but not dose-dependently, reduced hyperalgesia 50% its maximal effect. quickly absorbed; concentration stable 2 h, entered into brain. Although significantly decreased TRPV1-mediated calcium-influx potentially leading hyperthermia, did alter temperature. Oral inhibited and, despite antagonistic action penetration, influence thermoregulation, makes promising analgesic candidate.