Neuroprotective effects of the beta-carboline abecarnil studied in cultured cortical neurons and organotypic retinal cultures.

Abstract	Presently there is no neuroprotective pharmacological treatment of proven clinical safety and efficacy available. The purpose of this study was to investigate whether the beta-carboline, abecarnil (Abe), which has already passed clinical phase III trials in patients with anxiety disorders, is neuroprotective in in vitro models of cerebral ischemia or excitotoxicity. Abe (100 nM) protected cultured cortical neurons when applied 20 min before or 20 min after combined oxygen glucose deprivation (OGD). Furthermore, cultured cortical neurons were protected from NMDA excitotoxicity when Abe (100 nM) was administered 20 min before or concurrent with 100 microM NMDA. In contrast, in adult rat organotypic retinal cultures, Abe failed to protect retinal ganglion cells (RGCs) against glutamate (Glu) excitotoxicity. Thus, although our data demonstrate that Abe is a potential neuroprotectant in cultured neurons, the lack of effect in an organotypical model of Glu toxicity indicates that further study is required before Abe might be considered for human neuroprotection trials.
Authors	Karsten Ruscher, Stefan Rzeczinski, Elisabeth Thein, Dorette Freyer, Ilya V Victorov, Tim T Lam, Ulrich Dirnagl
Journal	Neuropharmacology (Neuropharmacology) Vol. 52 Issue 7 Pg. 1488-95 (Jun 2007) ISSN: 0028-3908 [Print] England
PMID	17449066 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Carbolines Excitatory Amino Acid Agonists Neuroprotective Agents beta Carotene N-Methylaspartate L-Lactate Dehydrogenase Glucose abecarnil
Topics	Analysis of Variance Animals Carbolines (pharmacology) Cell Death (drug effects) Cells, Cultured Cerebral Cortex (cytology) Dose-Response Relationship, Drug Drug Interactions Embryo, Mammalian Excitatory Amino Acid Agonists (pharmacology) Glucose (deficiency) Hypoxia (drug therapy) L-Lactate Dehydrogenase (metabolism) Male N-Methylaspartate (pharmacology) Neurons (drug effects) Neuroprotective Agents (pharmacology) Organ Culture Techniques Rats Rats, Wistar Retina (drug effects) beta Carotene (pharmacology)

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