Β-Carboline

β-Carboline (9H-pyrido[3,4-b]indole) represents the basic chemical structure for more than one hundred alkaloids and synthetic compounds. The effects of these substances depend on their respective substituent. Natural β-carbolines primarily influence brain functions but can also exhibit antioxidant effects. Synthetically designed β-carboline derivatives have recently been shown to have neuroprotective, cognitive enhancing and anti-cancer properties. The pharmacological effects of specific β-carbolines are dependent on their substituents. For example, the natural β-carboline harmine has substituents on position 7 and 1. Thereby, it acts as a selective inhibitor of the DYRK1A protein kinase, a molecule necessary for neurodevelopment. It also exhibits various antidepressant-like effects in rats by interacting with serotonin receptor 2A. Furthermore, it increases levels of the brain-derived neurotrophic factor (BDNF) in rat hippocampus. A decreased BDNF level has been associated with major depression in humans. The antidepressant effect of harmine might also be due to its function as a MAO-A inhibitor by reducing the breakdown of serotonin and noradrenaline. A synthetic derivative, 9-methyl-β-carboline, has shown neuroprotective effects including increased expression of neurotrophic factors and enhanced respiratory chain activity. This derivative has also been shown to enhance cognitive function, increase dopaminergic neuron count and facilitate synaptic and dendritic proliferation. It also exhibited therapeutic effects in animal models for Parkinson's disease and other neurodegenerative processes. However, β-carbolines with substituents in position 3 reduce the effect of benzodiazepine on GABA-A receptors and can therefore have convulsive, anxiogenic and memory enhancing effects. Moreover, 3-hydroxymethyl-beta-carboline blocks the sleep-promoting effect of flurazepam in rodents and - by itself - can decrease sleep in a dose-dependent manner.

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Concepts associés (16)

Β-Carboline

La β-carboline (9H-pyrido[3,4-b]indole) est une amine aromatique tricyclique. Elle est le noyau squelettique de base d'une classe de composés appelés β-carbolines. Le noyau β-carboline est constitué d'un cycle de pyridine (azine) fusionné avec un noyau d'indole par la cycle d'azole. Cette structure est très proche de celle de la tryptamine, où le bras éthylamine serait reconnecté au cycle indole par un carbone supplémentaire, pour produire la structure tricyclique.

Dopaminergic

Dopaminergic means "related to dopamine" (literally, "working on dopamine"), dopamine being a common neurotransmitter. Dopaminergic substances or actions increase dopamine-related activity in the brain. Dopaminergic brain pathways facilitate dopamine-related activity. For example, certain proteins such as the dopamine transporter (DAT), vesicular monoamine transporter 2 (VMAT2), and dopamine receptors can be classified as dopaminergic, and neurons that synthesize or contain dopamine and synapses with dopamine receptors in them may also be labeled as dopaminergic.

Indole

Lindole est un composé organique aromatique hétérocyclique. Le nom indole est dérivé de l'indigo, pigment bleu dont la molécule contient deux groupements indoles soudés. Il peut être décrit schématiquement comme étant formé d'un cycle benzénique et d'un cycle pyrrole accolés. Le doublet électronique porté par l'atome d'azote dans la représentation de Lewis participe à la délocalisation aromatique. Contrairement aux amines classiques, l'indole n'est donc pas une base puisque le caractère aromatique serait perdu en cas de réaction chimique mettant en jeu ce doublet.