Abstract
NS-417 (5-(4-Chlorophenyl)-8-methyl-6-7-8-9-tetrahydro-1-H-pyrrolo[3.2-h]isoquinoline-2,3-dione-3-oxim hydrochloric acid salt) belongs to a new chemical series of compounds. NS-417 rescued differentiated PC12 cells from death induced by withdrawal of serum and nerve growth factor. Furthermore, NS-417 stimulated neurotrophic factor-induced neurite outgrowth in undifferentiated PC12 cells. In accordance with this observation, NS-417 potentiated NGF-induced signaling, such as activation of the extracellular signal-regulated kinases ERK1 and ERK2 and the Akt kinase. NS-417 also enhanced ERK activation induced by 10 minutes stimulation with NGF, bFGF or EGF in PC12 cells. In addition to the effect in PC12 cells, NS-417 increased the number of tyrosine hydroxylase (TH) positive cells in cultures established from dissociated E14 rat ventral mesencephali.
MeSH terms
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Animals
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Cell Count
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Cell Survival / physiology
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Embryo, Mammalian / cytology
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Embryo, Mammalian / metabolism
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Enzyme Activation / drug effects
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Isoquinolines / chemistry
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Isoquinolines / pharmacology*
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Mesencephalon / embryology
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Mitogen-Activated Protein Kinases / metabolism
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Nerve Growth Factor / deficiency
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Nerve Growth Factor / pharmacology*
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Neurites / drug effects
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Neurites / physiology
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Neurons / cytology
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Neurons / enzymology
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Oximes / chemistry
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Oximes / pharmacology*
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PC12 Cells / drug effects
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PC12 Cells / physiology
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Protein Serine-Threonine Kinases*
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Proto-Oncogene Proteins / physiology
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Proto-Oncogene Proteins c-akt
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Rats
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Tetrahydroisoquinolines*
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Tyrosine 3-Monooxygenase / metabolism
Substances
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Isoquinolines
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NS-417 cpd
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Oximes
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Proto-Oncogene Proteins
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Tetrahydroisoquinolines
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Nerve Growth Factor
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Tyrosine 3-Monooxygenase
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Akt1 protein, rat
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Protein Serine-Threonine Kinases
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Proto-Oncogene Proteins c-akt
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Mitogen-Activated Protein Kinases