Comparison of the novel drug Ensaculin with MK-801 on the reduction of hydroxyl radical production in rat striatum after local application of glutamate

Peter Teismann, B Ferger

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)165-71
Number of pages7
JournalBrain Research
Volume857
Issue number1-2
Publication statusPublished - 28 Feb 2000

Fingerprint

Dizocilpine Maleate
Hydroxyl Radical
Glutamic Acid
Microdialysis
Pharmaceutical Preparations
Perfusion
Free Radicals
Salicylates
Neurodegenerative Diseases
Neurotransmitter Agents
Dementia
Wistar Rats
Ensaculin
2,3-dihydroxybenzoic acid

Keywords

  • Animals
  • Benzopyrans
  • Corpus Striatum
  • Dizocilpine Maleate
  • Excitatory Amino Acid Antagonists
  • Gentisates
  • Glutamic Acid
  • Hydroxybenzoic Acids
  • Hydroxyl Radical
  • Male
  • Microdialysis
  • Piperazines
  • Rats
  • Rats, Wistar
  • Receptors, N-Methyl-D-Aspartate
  • excitotoxicity
  • glutamate
  • hydroxyl radical
  • Ensaculin
  • microdialysis
  • neuroprotection
  • D-ASPARTATE ANTAGONISTS
  • ALZHEIMERS-DISEASE
  • OXIDATIVE STRESS
  • NMDA RECEPTOR
  • PARKINSONS-DISEASE
  • MPP+ NEUROTOXICITY
  • TERT-BUTYLNITRONE
  • SUBSTANTIA-NIGRA
  • NITRIC-OXIDE

Cite this

Comparison of the novel drug Ensaculin with MK-801 on the reduction of hydroxyl radical production in rat striatum after local application of glutamate. / Teismann, Peter; Ferger, B.

In: Brain Research, Vol. 857, No. 1-2, 28.02.2000, p. 165-71.

Research output: Contribution to journalArticle

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T1 - Comparison of the novel drug Ensaculin with MK-801 on the reduction of hydroxyl radical production in rat striatum after local application of glutamate

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N2 - 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.

AB - 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.

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KW - Hydroxybenzoic Acids

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KW - Microdialysis

KW - Piperazines

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KW - neuroprotection

KW - D-ASPARTATE ANTAGONISTS

KW - ALZHEIMERS-DISEASE

KW - OXIDATIVE STRESS

KW - NMDA RECEPTOR

KW - PARKINSONS-DISEASE

KW - MPP+ NEUROTOXICITY

KW - TERT-BUTYLNITRONE

KW - SUBSTANTIA-NIGRA

KW - NITRIC-OXIDE

M3 - Article

VL - 857

SP - 165

EP - 171

JO - Brain Research

JF - Brain Research

SN - 0006-8993

IS - 1-2

ER -