Neuroprotective effects of the beta-carboline abecarnil studied in cultured cortical neurons and organotypic retinal cultures.
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.
Ruscher
Karsten
K
Department of Experimental Neurology, Campus Charité Mitte, Berlin, Germany.
Rzeczinski
Stefan
S
Thein
Elisabeth
E
Freyer
Dorette
D
Victorov
Ilya V
IV
Lam
Tim T
TT
Dirnagl
Ulrich
U
D000704:Analysis of Variance; D000818:Animals; D002243:Carbolines / Q000494:pharmacology*; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004622:Embryo, Mammalian; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D005947:Glucose / Q000172:deficiency; D000860:Hypoxia / Q000188:drug therapy; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008297:Male; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009924:Organ Culture Techniques; D051381:Rats; D017208:Rats, Wistar; D012160:Retina / Q000187:drug effects*; D019207:beta Carotene / Q000494:pharmacology*
D002243:Carbolines; D018690:Excitatory Amino Acid Agonists; D018696:Neuroprotective Agents; D019207:beta Carotene; D016202:N-Methylaspartate; D007770:L-Lactate Dehydrogenase; D005947:Glucose; C062769:abecarnil