2-Aryl-3-indoleacetamides (FGIN-1): a new class of potent and specific ligands for the mitochondrial DBI receptor (MDR)

J Pharmacol Exp Ther. 1992 Sep;262(3):971-8.


The 2 aryl-3-indoleacetamides (FGIN-1) are a new class of compounds that potently (nM) and selectively bind to glial mitochondrial diazepam binding inhibitor (DBI) receptors (MDR), previously called peripheral benzodiazepine receptors, and increase mitochondrial steroidogenesis. The high-affinity binding of FGIN-1 to MDR derivatives depends on the following chemical characteristics: 1) the dialkylation of the amide; 2) the chain length of this alkyl substitution; and 3) the halogenation of aryl groups appended to the indole nucleus. FGIN-1 derivatives do not bind to gamma-aminobutyric acid (GABAA), GABAB, glycine, glutamate, dopamine, serotonin, opiate, cholecystokinin, beta adrenergic, cannabinoid or sigma receptors. FGIN-1-27 [N, N-di-n-hexyl 2-(4-fluorophenyl)indole-3-acetamide] enters the brain, and for this reason, this FGIN-1 compound is potent and efficacious behaviorally. Like the neurosteroid 3 alpha-5 alpha tetrahydrodeoxycorticosterone (THDOC), FGIN-1-27 delays the onset of isoniazid-induced convulsions, but fails to delay the onset of bicuculline-induced convulsions. However, differently from THDOC, the FGIN-1-27 anticonvulsant action is blocked by the isoquinoline carboxamide PK 11195. In the elevated plus maze test, FGIN-1-27 inhibits neophobia manner that is antagonized by PK 11195 but not by flumazenil. Because FGIN-1-27 binds to MDR and does not bind to the GABAA receptors, it is inferred that FGIN-1-27 may act on GABAA receptors indirectly, presumably via a stimulation of neurosteroid synthesis and release from glial cells.

MeSH terms

  • Acetamides / chemical synthesis*
  • Acetamides / metabolism
  • Acetamides / pharmacology
  • Animals
  • Bicuculline / toxicity
  • Binding, Competitive
  • Brain / drug effects
  • Brain / metabolism
  • Diazepam Binding Inhibitor
  • Indoleacetic Acids / chemical synthesis*
  • Indoleacetic Acids / metabolism
  • Indoleacetic Acids / pharmacology
  • Isoniazid / antagonists & inhibitors
  • Isoniazid / toxicity
  • Ligands
  • Mitochondria / drug effects
  • Mitochondria / metabolism*
  • Motor Activity / drug effects
  • Neuropeptides / metabolism*
  • Pregnenolone / biosynthesis
  • Rats
  • Rats, Inbred Strains
  • Receptors, GABA-A / drug effects
  • Receptors, GABA-A / metabolism
  • Seizures / chemically induced


  • Acetamides
  • Diazepam Binding Inhibitor
  • Indoleacetic Acids
  • Ligands
  • Neuropeptides
  • Receptors, GABA-A
  • Pregnenolone
  • Isoniazid
  • Bicuculline