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

• Published in: Neuropharmacology Vol. 52; no. 7; pp. 1488 - 1495
• Main Authors: Ruscher, Karsten, Rzeczinski, Stefan, Thein, Elisabeth, Freyer, Dorette, Victorov, Ilya V., Lam, Tim T., Dirnagl, Ulrich
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-06-2007
• Subjects: Abecarnil; Analysis of Variance; Animals; Basic Medicine; beta Carotene - pharmacology; Carbolines - pharmacology; Cell Death - drug effects; Cells, Cultured; Cerebral Cortex - cytology; Cortical neuron; culture; Dose-Response Relationship, Drug; Drug Interactions; Embryo, Mammalian; Excitatory Amino Acid Agonists - pharmacology; Excitotoxicity; Farmakologi och toxikologi; Glucose - deficiency; Hypoxia - drug therapy; L-Lactate Dehydrogenase - metabolism; Male; Medical and Health Sciences; Medicin och hälsovetenskap; Medicinska och farmaceutiska grundvetenskaper; N-Methylaspartate - pharmacology; Neurons - drug effects; Neuroprotection; Neuroprotective Agents - pharmacology; Organ Culture Techniques; organotypic retinal; Organotypic retinal culture; Oxygen glucose deprivation; Pharmacology and Toxicology; Rats; Rats, Wistar; Retina - drug effects; PBS; Neuroprotection; BSS; Abecarnil; Abe; CNS; OGD; RGC; div; GCL; Glu; LDH; Cortical neuron; Excitotoxicity; Organotypic retinal culture; GABA; NMDA; Oxygen glucose deprivation
• ISSN: 0028-3908; 1873-7064; 1873-7064
• DOI: 10.1016/j.neuropharm.2007.02.006

Presently there is no neuroprotective pharmacological treatment of proven clinical safety and efficacy available. The purpose of this study was to investigate whether the β-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
μM 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.