Anticonvulsant and analgesic in neuropathic pain activity in a group of new aminoalkanol derivatives

Bioorg Med Chem Lett. 2020 Aug 15;30(16):127325. doi: 10.1016/j.bmcl.2020.127325. Epub 2020 Jun 7.

Abstract

As part of the presented research, thirteen new aminoalkanol derivatives were designed and obtained by chemical synthesis. In vivo studies (mice, i.p.) showed anticonvulsant activity (MES) of nine compounds, and in the case of one compound (R,S-trans-2-((2-(2,3,5-trimethylphenoxy)ethyl)amino)cyclohexan-1-ol, 4) both anticonvulsant (ED50 MES = 15.67 mg/kg, TD50 rotarod = 78.30 mg.kg, PI = 5.00) and analgesic activity (OXA-induced neuropathic pain, active at 15 mg/kg). For selected active compounds additional in vitro studies have been performed, including receptor studies (5-HT1A), evaluation of antioxidant activity (DPPH assay), metabolism studies as well as safety panel (mutagenicity, safety in relation to the gastrointestinal flora, cytotoxicity towards astrocytes as well as impact on their proliferation and cell cycle).

Keywords: Aminoalkanol; Analgesic; Anticonvulsant; Astrocytes; Cytotoxicity; Intestinal flora; Metabolism; Mutagenicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Alcohols / chemistry
  • Amino Alcohols / pharmacology*
  • Analgesics / chemistry
  • Analgesics / metabolism
  • Analgesics / pharmacology*
  • Animals
  • Anticonvulsants / chemistry
  • Anticonvulsants / metabolism
  • Anticonvulsants / pharmacology*
  • Antioxidants / chemistry
  • Antioxidants / metabolism
  • Antioxidants / pharmacology*
  • Biphenyl Compounds / antagonists & inhibitors
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Humans
  • Molecular Structure
  • Neuralgia / drug therapy*
  • Picrates / antagonists & inhibitors
  • Structure-Activity Relationship

Substances

  • Amino Alcohols
  • Analgesics
  • Anticonvulsants
  • Antioxidants
  • Biphenyl Compounds
  • Picrates
  • 1,1-diphenyl-2-picrylhydrazyl