Overview
9-ME-BC, also known as 9-methyl-beta-carboline, is a synthetic derivative of the naturally occurring beta-carboline family of compounds, which are pyridoindole alkaloids found in various natural sources including certain foods, tobacco smoke, and endogenous biological tissues such as blood and brain matter. With a molecular formula of C12H10N2 and a molecular weight of 182.22, it is classified as a beta-carboline compound, distinguished from its naturally occurring relatives by the addition of a methyl group at the 9-position of its core structure. Researchers have taken interest in this compound due to its observed interactions with dopaminergic systems in laboratory settings, with published studies examining its effects on neurotrophic factor expression, monoamine oxidase activity, and neuronal growth patterns in preclinical models. Like all compounds in this reference database, 9-ME-BC is intended strictly for laboratory research purposes and is not approved for human consumption or therapeutic use.
Research & Bioactivity
9-ME-BC (9-methyl-β-carboline) is a methylated derivative of the β-carboline family of pyridoindole compounds, and researchers have studied it extensively in the context of dopaminergic neurobiology. Studies conducted in primary mesencephalic cell cultures have examined its effects on dopaminergic neuron differentiation, finding associations with increased expression of tyrosine hydroxylase, a key enzyme in dopamine synthesis, as well as enhanced neurite outgrowth. Research has also investigated the role of astrocytes in mediating some of these observed effects, including potential modulation of monoamine oxidase activity and stimulation of neurotrophic factor expression in glial cells. In animal model studies, researchers have examined whether administration of 9-ME-BC correlates with changes in hippocampal dopamine levels, dendritic branching, and synaptic density in relation to cognitive performance measures. Additional in vitro research has investigated the compound's potential anti-inflammatory properties alongside its apparent neuroprotective and neuroregenerative profiles in dopaminergic culture systems. The broader scientific interest in 9-ME-BC stems partly from the β-carboline class being associated with both neurotoxic and, under certain structural modifications, neurostimulative biological activity, making this compound a subject of ongoing preclinical investigation.
Published Research
9-Methyl-β-carboline inhibits monoamine oxidase activity and stimulates the expression of neurotrophic factors by astrocytes.
Keller S, Polanski WH, Enzensperger C, Reichmann H, Hermann A, et al. — 2020
β-Carbolines (BC) are pyridoindoles, which can be found in various exogenous and endogenous sources. Recent studies revealed neurostimulative, neuroprotective, neuroregenerative and anti-inflammatory effects of 9-methyl-BC (9-Me-BC). Additionally, 9-me-BC increased neurite outgrowth of dopaminergic neurons independent of dopamine uptake into these neurons. In this study, the role of astrocytes in neurostimulative, neuroregenerative and neuroprotective properties of 9-me-BC was further explored.9-Me-BC exerted anti-proliferative effects without toxic properties in dopaminergic midbrain and cortical astrocyte cultures. The organic cation transporter (OCT) but not the dopamine transporter seem to mediate at least part the effect of 9-me-BC on astrocytes. Remarkably, 9-me-BC stimulated the gene expression of several important neurotrophic factors for dopaminergic neurons like Artn, Bdnf, Egln1, Tgfb2 and Ncam1. These factors are well known to stimulate neurite outgrowth and to show neuroprotective and neuroregenerative properties to dopaminergic neurons against various toxins. Further, we show that effect of 9-me-BC is mediated through phosphatidylinositol 3-kinase (PI3K) pathway. Additionally, 9-me-BC showed inhibitory properties to monoamine oxidase (MAO) activity with an IC50 value of 1 µM for MAO-A and of 15.5 µM for MAO-B. The inhibition of MAO by 9-me-BC might contribute to the observed increased dopamine content and anti-apoptotic properties in cell culture after 9-me-BC treatment in recent studies. Thus, 9-me-BC have a plethora of beneficial effects on dopaminergic neurons warranting its exploration as a new multimodal anti-parkinsonian medication.
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, Enzensperger C, Bock J, et al. — 2012
β-Carbolines (BCs) belong to the heterogenous family of carbolines, which have been found exogenously, that is, in various fruits, meats, tobacco smoke, alcohol and coffee, but also endogenously, that is, blood, brain and CSF. These exogenous and endogenous BCs and some of their metabolites can exert neurotoxic effects, however, an unexpected stimulatory effect of 9-methyl-β-carboline (9-me-BC) on dopaminergic neurons in primary mesencephalic cultures was recently discovered. The aim of the present study was to extend our knowledge on the stimulatory effects of 9-me-BC and to test the hypothesis that 9-me-BC may act as a cognitive enhancer. We found that 10 days (but not 5 days) of pharmacological treatment with 9-me-BC (i) improves spatial learning in the radial maze, (ii) elevates dopamine levels in the hippocampal formation, and (iii) results after 10 days of treatment in elongated, more complex dendritic trees and higher spine numbers on granule neurons in the dentate gyrus of 9-me-BC-treated rats. Our results demonstrate that beyond its neuroprotective/neurorestorative and anti-inflammatory effects, 9-me-BC acts as a cognitive enhancer in a hippocampus-dependent task, and that the behavioral effects may be associated with a stimulatory impact on hippocampal dopamine levels and dendritic and synaptic proliferation.
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, Gille G — 2010
Beta-carbolines (BCs) are potential endogenous and exogenous neurotoxins that may contribute to the pathogenesis of Parkinson's disease. However, we recently demonstrated protective and stimulatory effects of 9-methyl-BC (9-me-BC) in primary dopaminergic culture. In the present study, treatment with 9-me-BC unmasked a unique tetrad of effects. First, tyrosine hydroxylase (TH) expression was stimulated in pre-existing dopa decarboxylase immunoreactive neurons and several TH-relevant transcription factors (Gata2, Gata3, Creb1, Crebbp) were up-regulated. Neurite outgrowth of TH immunoreactive (THir) neurons was likewise stimulated. The interaction with tyrosine kinases (protein kinase A and C, epidermal growth factor-receptor, fibroblast growth factor-receptor and neural cell adhesion molecule) turned out to be decisive for these observed effects. Second, 9-me-BC protected in acute toxicity models THir neurons against lipopolysaccharide and 2,9-dime-BC(+) toxicity. Third, in a chronic toxicity model when cells were treated with 9-me-BC after chronic rotenone administration, a pronounced regeneration of THir neurons was observed. Fourth, 9-me-BC inhibited the proliferation of microglia induced by toxin treatment and installed an anti-inflammatory environment by decreasing the expression of inflammatory cytokines and receptors. Finally, 9-me-BC lowered the content of alpha-synuclein protein in the cultures. The presented results warrant the exploration of 9-me-BC as a novel potential anti-parkinsonian medication, as 9-me-BC interferes with several known pathogenic factors in Parkinson's disease as outlined above. Further investigations are currently under way.
9-Methyl-beta-carboline up-regulates the appearance of differentiated dopaminergic neurones in primary mesencephalic culture.
Hamann J, Wernicke C, Lehmann J, Reichmann H, Rommelspacher H, et al. — 2008
beta-Carbolines (BCs) derive from tryptophan and its derivatives. They are formed endogenously in humans and mammals and occur inter alia in cooked meat and tobacco smoke. They have been detected in human brain, cerebrospinal fluid, and plasma. Up to now they were predominantly identified as compounds exhibiting neurotoxic actions. Since significantly higher amounts are present in parkinsonian patients, they are regarded as potential pathogenetic factors in Parkinson's disease. We identified for the first time a BC (9-methyl-BC; 9-me-BC) exerting neuroprotective and neuron-differentiating effects. Treatment of primary mesencephalic dopaminergic cultures with 9-me-BC inhibited the basal release of lactate dehydrogenase and reduced the number of cells stained with propidium iodide. Caspase-3 activity was decreased, the total protein content was unchanged and ATP content was increased. Furthermore, the expression of inflammation-related genes was reduced. The number of differentiated dopaminergic neurones was significantly increased and a wide array of neurotrophic/transcription factors (Shh, Wnt1, Wnt5a, En1, En2, Nurr1, Pitx3) and marker genes (Th, Dat, Aldh1a1) decisive for dopaminergic differentiation was stimulated. Consistently, the dopamine content was slightly, although non-significantly, increased and the dopamine uptake capacity was elevated. An anti-proliferative effect was observed in human neuroblastoma SH-SY5Y cells which is consistent with a reduced incorporation of bromodesoxyuridine into the DNA of primary mesencephalic cells. Whether the additional dopaminergic neurones in primary culture derive from dopaminergic precursor cells, previously tyrosine hydroxylase negative dopaminergic neurones or are the result of a transdifferentiation process remains to be established.