Experimental Evaluation of Anxiolytic and Analgesic Properties of a New Linear Methoxyphenyltriazaalkane Derivative with Cardiotropic Activity

Bull Exp Biol Med. 2021 Apr;170(6):763-768. doi: 10.1007/s10517-021-05149-9. Epub 2021 Apr 24.

Abstract

The anxiolytic and analgesic properties of compound ALM-802, a cardiotropic linear methoxyphenyltriazaalkane derivative, combining pharmacophore elements of p-FOX inhibitors trimetazidine and ranolazine were studied in vivo. In the elevated plus-maze test, ALM-802 after acute intraperitoneal administration in doses of 1-8 mg/kg dose-dependently prevented the development of anxiety in BALB/c mice. Chronic intraperitoneal administration of ALM-802 in a dose of 2 mg/kg to alcohol-preferring rats attenuated anxiogenesis induced by ethanol withdrawal. ALM-802 demonstrated antinociceptive activity in C57BL/6 mice during thermal stimulation of nociceptors in the hot plate test and during modeling of visceral pain in the acetic acid writhing test. Thus, ALM-802 exhibits anxiolytic and analgesic properties in the dose range corresponding to its anti-ischemic and antiarrhythmic effects.

Keywords: ALM-802; anxiety; nociception; trimetazidine.

MeSH terms

  • Animals
  • Anxiety / drug therapy
  • Anxiety / metabolism
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Nociception / drug effects*
  • Nociceptors / metabolism
  • Pain / drug therapy
  • Pain / metabolism
  • Trimetazidine / therapeutic use*

Substances

  • Trimetazidine