ליתיום - טיפול במאניה-דפרסיה, ובאלצהיימר. רפרנסים למנגנון הפעולה. - פוסט בבנייה
- Npint
- 2 באפר׳
- זמן קריאה 8 דקות
עודכן: 5 באפר׳
ליתיום הוא יסוד כימי בעל 3 אלקטרונים.
ליתיום אורוטאט (עפ צאט GPT)
Lithium orotate is a compound consisting of lithium and orotic acid. Its chemical formula is C₅H₃LiN₂O₄, and it is often found as a monohydrate. Structurally, lithium is non-covalently bound to the orotate ion, which is derived from orotic acid. The compound is used as a dietary supplement, although its medical efficacy is not widely supported by systematic reviews2.
Lithium orotate is typically synthesized by reacting lithium hydroxide or lithium carbonate with orotic acid. The reaction forms a salt where lithium ions are bound to orotate ions. The process may involve controlling the pH and temperature to ensure the formation of the desired compound. The resulting product is often purified and crystallized to obtain lithium orotate in its monohydrate form.
pH plays a crucial role in the synthesis of lithium orotate because it influences the ionization of orotic acid. Orotic acid has acidic properties and can exist in different ionic states depending on the pH of the solution. To ensure optimal binding of lithium ions to the orotate molecule, the pH must be carefully controlled to favor the formation of orotate ions rather than leaving orotic acid in its neutral form.
If the pH is too low (acidic), there may not be enough orotate ions available for the reaction. Conversely, if the pH is too high (alkaline), unwanted side reactions could occur, leading to impurities in the final product. Maintaining an appropriate pH ensures the efficiency and purity of the synthesis process.
Lithium orotate, a lesser-known form of lithium supplementation, has been gaining attention for its potential benefits in supporting mental health and cognitive function. Unlike the more widely recognized lithium carbonate, which is prescribed at high doses for the treatment of bipolar disorder, lithium orotate is available as an over-the-counter (OTC) supplement and is typically taken in much lower doses.
This article aims to provide a comprehensive overview of lithium orotate, exploring its history, mechanisms of action, potential benefits, and safety considerations. By examining the available scientific research and anecdotal evidence, we hope to shed light on the potential role of lithium orotate in promoting mental well-being and cognitive performance.
המאמר הנ"ל הוצע על ידי צאט GPT כך שיש לבדוק את נכונותו בעזרת מאמרים מדעיים).
כאן קטעים מהמאמר
Lithium orotate is a lithium salt of orotic acid, with the chemical formula C5H3LiN2O4. It contains lithium, an alkali metal, and orotic acid, a compound involved in nucleic acid metabolism. Lithium orotate is considered a more bioavailable form of lithium compared to other lithium salts.
What Is the Chemical Structure of Lithium Orotate?
The chemical structure of lithium orotate consists of a lithium ion (Li+) bound to an orotate anion (C5H3N2O4-). The orotate anion is derived from orotic acid, a heterocyclic compound containing a pyrimidine ring and a carboxyl group.
How Does Lithium Orotate Enhance Cognitive Function?
Lithium orotate is believed to modulate various neurotransmitters, including dopamine, serotonin, and GABA, in the brain. It may help regulate mood, reduce stress and anxiety, and improve focus and concentration. Lithium orotate also has neuroprotective effects, potentially preventing cognitive decline associated with aging or neurodegenerative diseases.
What Are the Biochemical Processes Influenced by Lithium Orotate?
Lithium orotate modulates neurotransmitter activity, inhibits GSK-3β enzyme, increases neurotrophic factors, reduces neuroinflammation, and enhances vitamin B12 and folate metabolism.
What Are the Primary Uses and Benefits of Lithium Orotate?
Lithium orotate is primarily used as a mood stabilizer and cognitive enhancer. It may help treat bipolar disorder, depression, and other mental health conditions. Lithium orotate is also being explored for its potential neuroprotective effects against neurodegenerative diseases.
בעיקרון זה מאמר פרסומת לתוסף מזון.
ליתיום קרבונט
פעילות:
פלסטיות מוחית: הגדלת מספר הדנדריטים ותאי העצב.
עיכוב שחרור של נוירואדרנלין וסרוטונין.
איזון ריכוזי מלחים בתא ומחוצה לו (משפיע על תקשורת בין נוירונים).
השפעה על מסלולי יצירת אנרגיה בתוך תאי העצב (מיטוכונדריות? ריכוז סרוטונין?)
הגדלה של פעילות של פקטורים בתוך התא המגינים על פעילות העצב.
(מתוך האתר של גרינהאוס משיבא).
בהתחלה יש שינויים בטעם ובריח (כמו שקורה בקורונה? קשר לדופמין?)
מתפנה דרך הכליה. להזהר מהתיבשות שמעלה ריכוז מלחים, ותרופות משתנות (כנ"ל).
ללתיום יש יתרונות מעבר ל"ייצוב מצב רוח". הוא מאזן הומהוסטזיס, ספציפית תאית, מיטוכונדריות - משק האנרגיה של תאי מוח, ומעודד פלסטיות מוחית, צמיחת תאי עצב ודנדריטים. בשנים האחרונות מגלים בו עניין לטיפול במחלות כמו אלצהיימר ופרקינסון.
ליתיום ואלצהיימר
Molecular mechanisms and therapeutic potential of lithium in Alzheimer's disease: repurposing an old class of drugs. Shen Y, Zhao M, Zhao P, Meng L, Zhang Y, Zhang G, Taishi Y, Sun L. Front Pharmacol. 024 Jul 11;15:1408462. doi: 10.3389/fphar.2024.1408462. PMID: 39055498; PMCID: PMC11269163.
Preclinical studies have shown that lithium can reduce amyloid deposition and tau phosphorylation, regulate autophagy, inflammation, oxidative stress, cholinergic and glucose metabolism, enhance neurogenesis and synaptic plasticity, maintain mitochondrial homeostasis, and improve cognitive function (Fiorentini et al., 2010; Toledo and Inestrosa, 2010; Zhang et al., 2011; Sudduth et al., 2012; Trujillo-Estrada et al., 2013; Wilson et al., 2017; Pan et al., 2018; Wilson et al., 2018; Habib et al., 2019; Liu M. et al., 2020; Wilson et al., 2020; Xiang et al., 2020; Xiang et al., 2021; Gherardelli et al., 2022; Lu et al., 2022; Wiseman et al., 2023).
Is there justification to treat neurodegenerative disorders by repurposing drugs? The case of alzheimer's disease, lithium, and autophagy. Damri O., Shemesh N., Agam G. (2020) Int. J. Mol. Sci. 22, 189. 10.3390/ijms22010189
Lithium is the prototype mood-stabilizer used for acute and long-term treatment of bipolar disorder. Cumulated translational research of lithium indicated the drug's neuroprotective characteristics and, thereby, has raised the option of repurposing it as a drug for neurodegenerative diseases. Lithium's neuroprotective properties rely on its modulation of homeostatic mechanisms such as inflammation, mitochondrial function, oxidative stress, autophagy, and apoptosis. This myriad of intracellular responses are, possibly, consequences of the drug's inhibition of the enzymes inositol-monophosphatase (IMPase) and glycogen-synthase-kinase (GSK)-3. Here we review lithium's neurobiological properties as evidenced by its neurotrophic and neuroprotective properties, as well as translational studies in cells in culture, in animal models of Alzheimer's disease (AD) and in patients, discussing the rationale for the drug's use in the treatment of AD.
Neurodegeneration in general relates to neuronal death in the central nervous system (CNS). Neurodegenerative diseases are characterized by gradual anatomical and/or physiological aberration of neuronal systems. They include Huntington’s disease (HD), Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD) [1].
In particular, we review and discuss pros and cons to repurpose lithium salts (lithium), the prototype drug for bipolar disorder, for the treatment of AD.
A recent study [45] demonstrated that enhanced mitophagy (elimination of defective mitochondria, a subtype of macroautophagy) abolishes AD-related tau hyper-phosphorylation in vitro and reverses memory impairment in transgenic tau mice in vivo, suggesting that impaired removal of defective mitochondria is a key factor in AD pathogenesis. These studies and similar ones point at autophagy mechanisms as potential therapeutic interventions in AD. Lithium is a well-known autophagy enhancer through inhibition of IMPase1 and induction of the mTOR-independent mechanism of autophagy enhancement [46]. Hence, lithium’s potential therapeutic use in treating AD should not be ruled out.
EF Fang, Y Hou, K Palikaras, BA Adriaanse… - Nature …, 2019 - nature.com
Accumulation of damaged mitochondria is a hallmark of aging and age-related
neurodegeneration, including Alzheimer's disease (AD). The molecular mechanisms of
impaired mitochondrial homeostasis in AD are being investigated. Here we provide
evidence that mitophagy is impaired in the hippocampus of AD patients, in induced
pluripotent stem cell-derived human AD neurons, and in animal AD models. In both amyloid-
β (Aβ) and tau Caenorhabditis elegans models of AD, mitophagy stimulation (through NAD+
Lithium Increases Serotonin Release and Decreases Serotonin Receptors in the Hippocampus
Science
25 Sep 1981
Vol 213, Issue 4515
pp. 1529-1531
Treiser, S., Cascio, C., O’Donohue, T., Thoa, N., Jacobowitz, D., & Kellar, K. (1981). Lithium increases serotonin release and decreases serotonin receptors in the hippocampus. Science, 213(4515), 1529–1531. doi:10.1126/science.6269180
The effects of long-term lithium administration on pre- and postsynaptic processes involved in serotonergic neurotransmission were measured in rat hippocampus and cerebral cortex. Long-term lithium administration increased both basal and potassium chloride-stimulated release of endogenous serotonin from the hippocampus but not from the cortex. Serotonergic receptor binding was reduced in the hippocampus but not in the cortex. These results suggest a mechanism by which lithium may stabilize serotonin neurotransmission.h,fi יתכן שמה שהם מציעים שהוא משחרר יותר סרוטונין, ומקטין מצד שני את מספר הקולטנים בפוסט סינפסה.
(אם זה ככה, זה יכול להוביל בזליגה של סרוטונין עודף שלא נקלט בתאים שמצפים לסרוטונין, ולקליטתם לתוך תאים שכנים של לדוגמה דופמין, הפעלת המיטוכונדריות שלהם לייצור מוגבר של אנרגיה, (ודופמין)...).
Alterations in neurotransmission at serotonin (5HT) synapses have been implicated in affective disorders,
and lithium has been reported to affect several serotonergic processes, including
synthesis (2, 3),
release (4), and
uptake of 5HT (5).
Long-term administration of lithium exerts specific effects on the binding of [3H]5HT to receptors in the rat brain (6, 7), resulting in a reduction of the density of [3H]5HT binding sites in the hippocampus, but not in the cerebral cortex (6).
2. A. K. S. Ho, H. H. Loh, F. Craves, R. J. Hitzemann, S. Gershon, Eur. J. Pharmacol. 10, 72 (1970).
The effect of prolonged lithium treatment on the dteady state levels and turnover rates of serotonin (5-HT), norepinephrine and dopamine was studied in the cerebral cortex, cerebellum, diencephalon, brain stem and hypothalamus. In normal rats, all 3 monoamines showed significant differences in the steady state levels and turnover rates among brain regions. The highest and lowest rates of synthesis of both 5-HT and norepinephrine were found in the hypothalamus and cerebellum respectively, while the rate of synthesis of dopamine was highest in the diencephalon and lowest in the cerebellum.
Prolonged lithium treatment produced a significant change on 5-HT levels only in the hypothalamus (46% reduction) and brain stem (26% reduction) but no significant change in the other regions. There was no significant alteration in both norepinephrine and dopamine levels in any of the 5 discrete areas studied. The turnover rate of 5-HT was slight but not significantly changed by lithium in whole brain studies. However, a significant effect was observed in regional studies. The cerebellum showed a 37% increase in the synthesis rate whereas the hypothalamus showed a 51.1% reduction. The turnover rates of both norepinephrine and dopamine were not significantly affected in most brain regions by prolonged lithium treatment. The mean concentration of lithium in the serum and whole brain were 1.96 meq/l and 0.88 meq/kg respectively. These findings suggest that there may be a variable relationship between the tissue concentration and synthesis rates of the monoamines under both normal conditions and lithium treatment. It was concluded that the observed differences in the action of lithium on monoamines in the regions studied may be related to the morphology of these discrete areas.
3. S. Knapp and A. J. Mandell, Science 180, 645 (1973).
Short-term treatment with lithium chloride stimulates the uptake of tryptophan and its conversion to serotonin by striate synaptosomes. Preincubation of striate synaptosomes with L-tryptophan and in vivo administration of L-tryptophan appear to act in a similar manner. Midbrain tryptophan hydroxylase activity is reduced in temporal continuity with the lithium-induced activation of tryptophan uptake and conversion. By 10 days, conversion of tryptophan to serotonin in nerve endings becomes a joint function of the maintained increased uptake of tryptophan and a decreased level of tryptophan hydroxylase activity in nerve endings. The occurrence of this delayed alteration corresponds in time to the previously described axoplasmic flow rate for tryptophan hydroxylase.
4. R. I. Katz, T. N. Chase, I. J. Kopin, ibid. 162, 466 (1968); R. I. Katz and 1. J. Kopin, Biochem. Pharmacol. 18, 1935 (1968).
5. E. F. Friedman and S. Gershon, Int. Congr. Pharmacol. 1978, 855 (Abstr.) (1978).
6. S. Treiser and K. J. Kellar, Eur. J. Pharmacol. 64, 183 (1980).
7. A. Maggi and S. J. Enna, J. Neurochem. 34, 888 (1980).
Lithium Increases Serotonin Release and Decreases Serotonin Receptors in the Hippocampus Science
25 Sep 1981
Vol 213, Issue 4515
pp. 1529-1531
The effects of long-term lithium administration on pre- and postsynaptic processes involved in serotonergic neurotransmission were measured in rat hippocampus and cerebral cortex. Long-term lithium administration increased both basal and potassium chloride-stimulated release of endogenous serotonin from the hippocampus but not from the cortex. Serotonergic receptor binding was reduced in the hippocampus but not in the cortex. These results suggest a mechanism by which lithium may stabilize serotonin neurotransmission.
Gough, N. (2005). STKE: Balancing Axons and Dendrites. Science, 307(5710), 647b–647b. doi:10.1126/science.307.5710.647b
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