Neuroscience Research Compound · For laboratory research use only
Also known as 9-Methyl-beta-carboline
9-Methyl-beta-carboline (9-Me-BC, also 9-methylnorharmane) is a beta-carboline, one of a class of pyridoindoles derived from tryptophan and its derivatives that occur in sources such as cooked meat and tobacco smoke and have been detected in human brain, cerebrospinal fluid and plasma1,5. Many beta-carbolines have been studied as potential neurotoxins; 9-Me-BC was reported in 2008 as an exception, with protective and differentiating effects in primary dopaminergic culture1.
The published literature is small. It consists mainly of primary midbrain and astrocyte culture studies and a few rat studies1,2,3,4,5, together with photochemical work on 9-methyl-beta-carbolines as photosensitisers6.
As described in the research literature
As described in the research literature, treatment of primary mesencephalic cultures with 9-Me-BC increased the number of differentiated tyrosine hydroxylase-positive dopaminergic neurons and stimulated transcription factors and marker genes involved in dopaminergic differentiation, while reducing markers of cell death and the expression of inflammation-related genes1. Follow-up work linked the stimulation of tyrosine hydroxylase expression and neurite outgrowth to interactions with protein kinases A and C, EGF and FGF receptors and NCAM2.
In astrocyte cultures, 9-Me-BC stimulated expression of neurotrophic factor genes including Artn, Bdnf, Tgfb2 and Ncam1 through a PI3K-dependent pathway, with the organic cation transporter rather than the dopamine transporter appearing to mediate part of the effect. The same study measured inhibition of monoamine oxidase, reporting IC50 values of 1 µM for MAO-A and 15.5 µM for MAO-B5.
What published studies have examined
Primary mesencephalic cultures were used to examine lactate dehydrogenase release, caspase-3 activity, dopaminergic differentiation genes, dopamine content and uptake1. Later work examined neurite outgrowth, protection against lipopolysaccharide and 2,9-dimethyl-beta-carbolinium toxicity, recovery after chronic rotenone exposure, microglial proliferation and alpha-synuclein content2.
Rats pretreated with the neurotoxin MPP+ were used to examine striatal dopamine, stereological counts of tyrosine hydroxylase-immunoreactive cells in the substantia nigra, respiratory chain complex I activity and neurotrophin gene expression in rats given 9-Me-BC3.
Sources [3]
A rat study examined spatial learning in the radial maze, dopamine levels in the hippocampal formation, and dendritic complexity and spine numbers of granule neurons in the dentate gyrus4.
Sources [4]
Midbrain and cortical astrocyte cultures were used to examine proliferation, transporter dependence and neurotrophic factor gene expression, and MAO-A and MAO-B inhibition was measured in vitro5. A correction to this paper was published in 2022.
Sources [5]
9-Methyl-beta-carbolines, including 9-methylnorharmane, act as photosensitisers. Under UVA excitation at physiological pH they generated oxidised purines, single-strand breaks and cyclobutane pyrimidine dimers in DNA, which is relevant to light-protected handling6.
Sources [6]
9-Methyl-beta-carboline up-regulates the appearance of differentiated dopaminergic neurones in primary mesencephalic culture.
Hamann J, Wernicke C, Lehmann J, et al. Neurochemistry International, 2008.
The exceptional properties of 9-methyl-beta-carboline: stimulation, protection and regeneration of dopaminergic neurons coupled with anti-inflammatory effects.
Polanski W, Enzensperger C, Reichmann H, et al. Journal of Neurochemistry, 2010.
9-Methyl-beta-carboline has restorative effects in an animal model of Parkinson's disease.
Wernicke C, Hellmann J, Zieba B, et al. Pharmacological Reports, 2010.
9-Methyl-β-carboline-induced cognitive enhancement is associated with elevated hippocampal dopamine levels and dendritic and synaptic proliferation.
Gruss M, Appenroth D, Flubacher A, et al. Journal of Neurochemistry, 2012.
9-Methyl-β-carboline inhibits monoamine oxidase activity and stimulates the expression of neurotrophic factors by astrocytes.
Keller S, Polanski WH, Enzensperger C, et al. Journal of Neural Transmission, 2020.
Mechanisms of DNA damage by photoexcited 9-methyl-β-carbolines.
Vignoni M, Rasse-Suriani FA, Butzbach K, et al. Organic & Biomolecular Chemistry, 2013.
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