Ensaculin interacts with various
neurotransmitter systems (e.g., dopaminergic, serotoninergic, glutamatergic) and was originally designed for the treatment of
dementia. In the present study
Ensaculin was tested for its possible reduction of
glutamate-induced
hydroxyl free radical formation in vivo. The microdialysis experiment was carried out in non-anaesthetized Wistar rats, which were implanted with a microdialysis probe into the striatum.
Salicylate (10 nmol/2 microl/min) was incorporated into the perfusion fluid to measure indirectly
hydroxyl radicals indicated by
2,3-dihydroxybenzoic acid (DHBA) formation. After baseline recording,
glutamate (100 or 500 nmol/2 microl/min) was perfused through the microdialysis probe (CMA 12, 4 mm, flow rate 2 microl/min).
Ensaculin (0.1, 1 and 10 mg/kg),
MK-801 (1 mg/kg) or saline was injected i.p. 20 min after the onset of
glutamate perfusion (500 nmol/2 microl/min).
Glutamate (100 nmol/2 microl/min) and (500 nmol/2 microl/min) perfusion produced a 2.6- and 17-fold increase of 2,3-DHBA, respectively. Treatment with
Ensaculin (1 and 10 mg/kg i.p. ) significantly antagonized the formation of 2,3-DHBA, to values of 60.5% and 56.7% of control levels, respectively. In comparison,
MK-801 attenuated 2,3-DHBA levels, to values of 65.8% compared to control values.
Ensaculin may be useful in the treatment of
neurodegenerative disorders associated with elevated
hydroxyl free radicals and excitotoxicity.