[PHARMACOLOGICAL STUDY OF NEW COMPOUNDS ACTING AS REGULATORS OF 18-KDA TRANSLOCATOR PROTEIN LIGANDS]

Eksp Klin Farmakol. 2016;79(1):7-11.
[Article in Russian]

Abstract

The interaction of new original 1-arylpyrrolo[1,2-a]pyrazine-3-carboxamide derivatives with mitochondrial translocator protein (MTP) 18 kDa has been studied by radioligand binding assay. Compounds GML-1 (Ki = 5.2 x 10⁻⁸ M) and GML-3 (Ki = 5.3 x 10⁻⁷ M) exhibit high binding affinity for MTP. GML-1 and GML-3 in a dose range of 0.1-1 mg/kg (i.p.) demonstrated anxiolytic-like effects in the elevated plus-maze test in CD-1 mice, which were blocked by the MTP selective antagonist PK11195. The data obtained on the molecular target, anxiolytic-like effects and low toxicity GML-1 and GML-3 suggest that these compounds are promising for further investigation as anxiolytics.

MeSH terms

  • Animals
  • Anti-Anxiety Agents / chemistry
  • Anti-Anxiety Agents / pharmacology*
  • Carrier Proteins / agonists*
  • Carrier Proteins / metabolism*
  • Isoquinolines / chemistry
  • Isoquinolines / pharmacology*
  • Maze Learning / drug effects*
  • Mice

Substances

  • Anti-Anxiety Agents
  • Carrier Proteins
  • Isoquinolines
  • microsomal triglyceride transfer protein
  • PK 11195