Alchemica Posted May 20 Share Posted May 20 (edited) Anyone used theobromine for a sustained period and found it useful for attention deficits? The cacao flavonols would likely be synergistic over theobromine alone It's only an animal model study so far but potentially an option Theobromine improves hyperactivity, inattention, and working memory via modulation of dopaminergic neural function in the frontal cortex of spontaneously hypertensive rats https://doi.org/10.1039/D4FO00683F While it has a nonselective PDE inhibition effect greater than caffeine, oral theobromine inhibits mTOR signalling in vivo which is of relevance to multiple conditions [1] and elevates cerebral brain-derived neurotrophic factor and facilitates learning in animal models [2] and orally supplemented, it upregulates the pathways in the mPFC, which may then improve working memory in animal models [3]. MTXs act through a variety of different molecular mechanisms: mobilization of intracellular calcium, inhibition of phosphodiesterases (PDEs), modulation of gamma-amino butyric acid (GABAA) receptors, inhibition of high affinity ATP-dependent cyclic nucleotide transporters and antagonism of adenosine receptors. The plasma levels that could be reached under dietary regimes and the fact that MTXs readily cross the blood-brain barrier indicate that these drugs inhibit adenosine receptors in the CNS; higher doses may be required to mobilize intracellular calcium, inhibit PDEs or modulate GABAA receptors, or to unselectively inhibit ABCC5 and ABCC4 transporters. Moreover, despite the physiological relevance, also under scrutiny is how caffeine, theobromine and theophylline are able to interact with native double helical DNA [1] https://www.ncbi.nlm.nih.gov/pubmed/30451374 [2] https://www.ncbi.nlm.nih.gov/pubmed/27833051 [3] https://www.ncbi.nlm.nih.gov/pubmed/31010016 Edited May 21 by Alchemica 1 Quote Link to comment Share on other sites More sharing options...
saguaro Posted May 27 Share Posted May 27 Nice post! This could be insightful into the mechanism by which caffeine / caffeinated beverage consumption reduces incidence of neurodegenerative disease. I'm a bit confused by this statement: "Moreover, despite the physiological relevance, also under scrutiny is how caffeine, theobromine and theophylline are able to interact with native double helical DNA" What is meant by interact with native double helical DNA in this instance? As far as I'm aware MTXs aren't mutagens, MTX actions should be accounted for by acute signalling mechanisms and effects on transcription. Quote Link to comment Share on other sites More sharing options...
Alchemica Posted May 28 Author Share Posted May 28 5 hours ago, saguaro said: What is meant by interact with native double helical DNA in this instance? As far as I'm aware MTXs aren't mutagens, MTX actions should be accounted for by acute signalling mechanisms and effects on transcription. They "... interact with all the base pairs of DNA (A-T; G-C) and phosphate group through hydrogen bond (H-bond) interaction." Probably similar to things like beta-carbolines that interact in the way below. Other ones like coralyne and berberine also form a complex with DNA, probably by intercalation, giving rise to therapeutic effects in things like cancer. Johnson, I.M., Prakash, H., Prathiba, J., Raghunathan, R., Malathi, R. Spectral analysis of naturally occurring methylxanthines (theophylline, theobromine and caffeine) binding with DNA. PLoS One 2012, 7, e50019. https://doi.org/10.1371/journal.pone.0050019 Quote Link to comment Share on other sites More sharing options...
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