Potential antidepressant properties of IDN 5491 (hyperforin- trimethoxybenzoate), a semisynthetic ester of hyperforin

Luigi Cervo, Tiziana Mennini, Marco Rozio, Charlotte Blanche Ekalle-Soppo, Alessandro Canetta, Silvia Burbassi, Giovanna Guiso, Lorenza Pirona, Antonella Riva, Paolo Morazzoni, Silvio Caccia, Marco Gobbi

Research output: Contribution to journalArticlepeer-review

Abstract

Hyperforin is one of the possible active principles mediating the antidepressant activity of Hypericum perforatum L. extracts. The ester derivative IDN 5491 (hyperforin-trimethoxybenzoate) showed antidepressant-like properties in the forced swimming test (FST) in rats, with no effect on open-field activity, when given as three intraperitoneal injections in 24 h at 3.125 and 6.25 mg/kg. The plasma concentrations of IDN 5491 were 30-50 μM, and those of hyperforin much lower but still close to those after effective doses of hyperforin-dicyclohexylammonium and Hypericum extract. This suggests that hyperforin plays a role in the antidepressant-like effect of the ester and of Hypericum extract. In vitro binding and uptake data showed that IDN 5491 is inactive on a wide panel of CNS targets at a concentration (14 μM) much higher than that measured in the brain of treated rats (0.3 μM). Like the extract, the antidepressant-like effect of IDN 5491 was blocked by (-)-sulpiride, a selective D2 receptor antagonist and by BD-1047, a selective sigma1 antagonist. Ex-vivo binding studies showed that brain sigma1 receptors are occupied after in vivo treatment with IDN 5491, possibly by an unknown metabolite or by endogenous ligand induced by hyperforin.

Original languageEnglish
Pages (from-to)211-218
Number of pages8
JournalEuropean Neuropsychopharmacology
Volume15
Issue number2
DOIs
Publication statusPublished - Mar 2005

Keywords

  • Antidepressant-like activity
  • Brain-to-plasma distribution ratio
  • Hypericum perforatum L. extracts
  • IDN 5491 (hyperforin-trimethoxybenzoate)
  • Rat

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Biological Psychiatry
  • Neurology
  • Pharmacology
  • Psychology(all)

Fingerprint Dive into the research topics of 'Potential antidepressant properties of IDN 5491 (hyperforin- trimethoxybenzoate), a semisynthetic ester of hyperforin'. Together they form a unique fingerprint.

Cite this