NS 1231, a novel compound with neurotrophic-like effects in vitro and in vivo.

Abstract

NS 1231 [5-(4-chlorophenyl)-6,7,8,9-tetrahydro-1H-pyrrolo-[3.2-h]naphthalene-2,3-dione-3-oxime] belongs to a chemical series of compounds, which exhibit neurotrophic-like activities. In vitro, NS 1231 rescued nerve growth factor (NGF)-differentiated PC12 cells from death induced by withdrawal of trophic factors. In addition, NS 1231 stimulated NGF-induced neurite outgrowth of undifferentiated PC12 cells. At the molecular level, NS 1231 enhanced NGF-induced signalling events, such as TrkA phosphorylation at the Shc-binding site Tyr490 as well as ERK activation in PC12 cells. Moreover, NS 1231 reduced NMDA-induced excitotoxicity in organotypic hippocampal slice cultures. In a gerbil model of transient global ischaemia, treatment with NS 1231 reduced the delayed loss of neurons in the hippocampal CA1 layer. Furthermore, NS 1231 treatment resulted in a 43% reduction in total infarct volume in the mouse middle cerebral artery occlusion (MCAO) model. The present data thus implicate a therapeutic potential of NS 1231 or structural analogues in treatment of cerebral ischaemia.

• Authors: Lone Dagø, Christian Bonde, Dan Peters, Arne Møller, Signe Farsø Bomholt, J Barbara P Hartz, Morten Meyer, Jørgen Drejer, Mette Grønborg
• Journal: Journal of neurochemistry (J Neurochem) Vol. 81 Issue 1 Pg. 17-24 (Apr 2002) ISSN: 0022-3042 [Print] England
• PMID: 12067229 (Publication Type: Journal Article)

Chemical References

• Indoles
• NS 1231
• Nerve Growth Factors
• Neuroprotective Agents
• Oximes
• N-Methylaspartate
• Nerve Growth Factor
• Receptor, trkA
• Mitogen-Activated Protein Kinases

Topics

• Animals
• Cell Survival (drug effects)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Drug Evaluation, Preclinical
• Enzyme Activation (drug effects)
• Gerbillinae
• Hippocampus (drug effects, pathology)
• In Vitro Techniques
• Indoles (pharmacology)
• Infarction, Middle Cerebral Artery (drug therapy, pathology)
• Ischemic Attack, Transient (drug therapy, pathology)
• Mice
• Mitogen-Activated Protein Kinases (metabolism)
• N-Methylaspartate (toxicity)
• Nerve Growth Factor (pharmacology)
• Nerve Growth Factors (pharmacology)
• Neurites (drug effects)
• Neurons (cytology, drug effects, pathology)
• Neuroprotective Agents (pharmacology)
• Oximes (pharmacology)
• PC12 Cells
• Phosphorylation (drug effects)
• Rats
• Receptor, trkA (metabolism)
• Signal Transduction (drug effects)