Background and aims: SZV 1287 [3-(4,5-diphenyl-1,3-oxazol-2-yl) propanal oxime] is our patented metabolism-activated multi-targeting drug under preclinical development. It inhibits semicarbazide-sensitive amine oxidase, its metabolite, oxaprozine, produced mainly under acidic conditions, blocks cyclooxygenases, and antagonizes Transient Receptor Potential Ankyrin 1 and Vanilloid 1 (TRPV1) receptors. We investigated the effects and kinetics of SZV 1287 in a rodent model of traumatic neuropathy. 
Methods: Traumatic neuropathic pain was induced by partial unilateral sciatic nerve ligation. The antihyperalgesic effect of enterosolvent and non-enterosolvent SZV 1287 capsules (10, 20, 50, 100 and 200 mg/kg, p.o.) was investigated by aesthesiometry. due to its TRPV1 antagonistic action, core body temperature was measured by telemetry and termometry. Distribution was determined by 11C-SZV 1287 in vivo PET/MRI, brain and plasma concentrations by HPLC, albumin binding by fluorimetry.  
Results: SZV 1287 administered in enterosolvent capsules induced significant, dose-dependent antihyperalgesic effect with 47±12% efficacy and 16.64 mg/kg potency (ED50). 1ºC degree, 70-min long core body temperature increase was detected only in case of the 50 mg/kg i.p. dose, but not after the administration of the effective oral doses. Its very fast blood-brain barrier penetration was shown both in vivo and ex vivo. It has stable albumin binding (logK~5,6). 
Conclusions: Oral SZV 1287 exerts potent antihyperalgesic effect under neuropathic condition that is likely to have a central site of action and despite TRPV1 antagonistic action, it does not influence thermoregulation. Enterosolvent capsule is desired for its administration to achieve stable absorption. 
Acknowledgements: National Brain Research Program 20017-1.2.1-NKP-2017-00002, GINOP-2.2.1-15-2016-00020, EFOP-3.6.2-16-2017-00008, EFOP-3.6.1-16-2016-00004

ANALGESIC EFFECTS OF THE NOVEL SEMICARBAZIDE-SENSITIVE AMINE OXIDASE INHIBITOR SZV 1287 IN RODENT MODELS OF NEUROPATHIC PAIN