Neurogenic Potential Assessment and Pharmacological Characterization of 6‑Methoxy-1,2,3,4-tetrahydro-β-carboline (Pinoline) and Melatonin–Pinoline Hybrids

6-Methoxy-1,2,3,4-tetrahydro-β-carboline (pinoline) and N-acetyl-5-methoxytryptamine (melatonin) are both structurally related to 5-hydroxytryptamine (serotonin). Here we describe the design, synthesis, and characterization of a series of melatonin rigid analogues resulting from the hybridization of...

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Published in:ACS chemical neuroscience 2015-05, Vol.6 (5), p.800-810
Main Authors: de la Fuente Revenga, Mario, Pérez, Concepción, Morales-García, José A, Alonso-Gil, Sandra, Pérez-Castillo, Ana, Caignard, Daniel-Henri, Yáñez, Matilde, Gamo, Ana M, Rodríguez-Franco, María Isabel
Format: Article
Language:English
Subjects:
Animals
Antioxidants - chemical synthesis
Antioxidants - chemistry
Antioxidants - pharmacology
Carbolines - chemical synthesis
Carbolines - chemistry
Carbolines - pharmacology
Humans
Male
Melatonin - chemical synthesis
Melatonin - chemistry
Melatonin - pharmacology
Neural Stem Cells - drug effects
Neurogenesis - drug effects
Rats
Rats, Wistar
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Summary:6-Methoxy-1,2,3,4-tetrahydro-β-carboline (pinoline) and N-acetyl-5-methoxytryptamine (melatonin) are both structurally related to 5-hydroxytryptamine (serotonin). Here we describe the design, synthesis, and characterization of a series of melatonin rigid analogues resulting from the hybridization of both pinoline and melatonin structures. The pharmacological evaluation of melatonin–pinoline hybrids comprises serotonergic and melatonergic receptors, metabolic enzymes (monoamine oxidases), antioxidant potential, the in vitro blood-brain barrier permeability, and neurogenic studies. Pinoline at trace concentrations and 2-acetyl-6-methoxy-1,2,3,4-tetrahydro-β-carboline (2) were able to stimulate early neurogenesis and neuronal maturation in an in vitro model of neural stem cells isolated from the adult rat subventricular zone. Such effects are presumably mediated via serotonergic and melatonergic stimulation, respectively.
ISSN:1948-7193
1948-7193
DOI:10.1021/acschemneuro.5b00041