Gender difference in epileptogenic effects of 2-BFI and BU224 in mice

Eur J Pharmacol. 2013 Oct 15;718(1-3):81-6. doi: 10.1016/j.ejphar.2013.09.016. Epub 2013 Sep 17.


Imidazoline I2 receptors are involved in pain modulation and psychiatric disorders and its ligands may represent a new therapeutic strategy against pain and depression. In particular, 2-BFI and BU224 are the two most widely studied I2 receptor ligands and have antinociceptive and antidepressant-like activities in rodents. However, little is known of the toxicological effects and potential gender differences of these I2 receptor ligands. This study examined the epileptogenic activities of 2-BFI and BU224 in male and female mice and also examined their underlying receptor mechanisms. 2-BFI (10-40 mg/kg, i.p.) and BU224 (10-40 mg/kg) produced epileptic seizures in a dose-related manner, as did the epileptogenic agent, pentylenetetrazole (PTZ, 15-60 mg/kg). However, female mice were significantly more sensitive than male mice in all the measures. The commonly used I2 receptor antagonist, idazoxan (10mg/kg), did not block the onset and magnitude of the epileptic seizures or lethality induced by 2-BFI and BU224. When studied in combination, PTZ potentiated the epileptogenic effect of 2-BFI and BU224. The lack of antagonism by idazoxan of the epileptogenic activities of 2-BFI and BU224 suggests that the epileptogenic effects of 2-BFI and BU224 are mediated by non-imidazoline I2 receptors and that I2 receptors remain a viable therapeutic target for neurological disorders such as pain.

Keywords: 2-BFI; BU224; Idazoxan; Imidazoline I(2) receptor; Mice; Seizure.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Benzofurans / adverse effects*
  • Benzofurans / metabolism
  • Female
  • Imidazoles / adverse effects*
  • Imidazoles / metabolism
  • Imidazoline Receptors / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Seizures / chemically induced*
  • Seizures / physiopathology*
  • Sex Characteristics*


  • BU 224
  • Benzofurans
  • Imidazoles
  • Imidazoline Receptors
  • imidazoline receptor 2
  • 2-(2-benzofuranyl)-2-imidazoline