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Onemorestep

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  1. Here is a population study. This drug is certainly not without risk but it is good to know what those risk % are and what it means if they happen. Background: Flunarizine (Fz) is a first-line prophylactic medication that is widely used in migraine. However, Fz has been recognized as a potential cause of drug-induced parkinsonism for a long time. However, to our knowledge, there has been no population-based subgroup analyses for Fz-induced parkinsonism (FIP) in migraine patients. Methods: Data were obtained from the Taiwan’s National Health Insurance Research Database. The study comprised 6,470 migraine patients who were divided into two groups, based on their exposure or non-exposure to Fz. Results: During the study period (2000–2012), the incidence rate of parkinsonism was 1.92 and 8.72 per 1,000 person-years in the control and Fz -treated groups, respectively. In the study population, the adjusted hazard ratio was 4.07 (95% confidence interval CI: 2.84–5.85). In 45–64-year old subjects and ≥ 65-year old subjects, the risk of FIP was 3.18 times (95% CI = 1.63–6.20) and 4.89 times (95% CI = 3.09–7.72) more than that in the controls. The Fz-treated subjects with comorbidities also had a higher risk (4.54, 95% CI: 3.14-6.57). An average annual cumulative Fz dose > 445 mg was accompanied by the greatest risk of FIP; Fz use for >60 days is a cut-off point for predicting future FIP. Conclusion: At the population level, this study showed a complete picture of FIP in migraine patients. FIP is associated with older age, history of comorbidities, exposure to high-dose of Fz, and longer duration of exposure to Fz.
  2. It’s not Parkinson’s. It’s parkinsomism. Introduction Cinnarizine (CNZ) and flunarizine (FNZ) belong to the calcium channel blockers class of medication. Main text The aim of this literature review is to evaluate the clinical epidemiological profile, pathological mechanisms, and management of CNZ/FNZ-associated movement disorder (MD). Relevant reports in six databases were identified and assessed by two reviewers without language restriction. One hundred and seventeen reports containing 1920 individuals who developed a CNZ/FNZ-associated MD were identified. The MD encountered were 1251 parkinsonism, 23 dyskinesias, 11 akathisia, 16 dystonia, and 5 myoclonus, and in the group not clearly defined, 592 extrapyramidal symptoms, 19 tremors, 2 bradykinesia, and 1 myokymia. The predominant sex was female with a percentage of 72.69% (466/641). The mean age was 74.49 (SD, 7.88) years. The mean CNZ dose was 148.19 mg (SD, 42.51) and for the FNZ dose, 11.22 mg (5.39). The mean MD onset and recovery were 1.83 years (SD, 1.35) and 3.71 months (SD, 1.26). In the subgroup of subjects that had improvement of the symptoms, the complete recovery was achieved within 6 months of the drug withdrawal in almost all subjects (99%). The most common management was drug withdrawal. A complete recovery was observed in 93.77% of the patients (437/466). https://ejnpn.springeropen.com/articles/10.1186/s41983-020-00197-w
  3. I encourage 2 months of clonazepam 1 mg twice daily followed by a taper over 30 days using a mg scale to do daily dose reductions. There is a study that showed that patients on this protocol faired better at the 8th month mark than their peers who did not do this. If i had to guess, there is an accumulative effect in the few months after onset that can be dampened. I did this therapy and the second time i got hppd it worked well
  4. No. But it’s been about 8 years since I got hppd and visuals are mostly gone. Psych symptoms remained
  5. I have tried it. It felt great. Weirdly, had opposite effects compared to baclofen for 5 hours and then switched to muscle relation and antidepressant effect. I have paws from prior baclofen use so I can not use. I also believe withdrawals will be present but no where near to the degree that benzos would cause.
  6. I read about a doctor using c60 fullerene to sure his flox. I take it daily.
  7. “The anticonvulsant drug lamotrigine has been shown to produce strong antidepressant effects in the treatment of bipolar disorder patients. Our previous studies have demonstrated that brain derived neurotrophic factor (BDNF) signaling plays an important role in regulating its behavioral actions in several rodent models of depression. The current study extends earlier work on BDNF and explores the role of another important neurotrophin vascular endothelial growth factor (VEGF) in regulating the antidepressant actions of lamotrigine. The results showed that chronic administration of 30 mg/kg lamotrigine (14 days) normalized the down-regulated frontal and hippocampal VEGF protein expression as well as the behavioral deficits induced by chronic unpredictable stress. In addition, pharmacological inhibition of VEGF signaling by infusion of SU5416, a selective Flk-1 receptor inhibitor, blocks the antidepressant effects of lamotrigine in all behavioral paradigms. Taken together, this study provides further evidence that VEGF is also an essential regulator for the antidepressant effects of lamotrigine.” vegf is complex. There are several subgroups of vegf and they do different things. https://pubmed.ncbi.nlm.nih.gov/22033393/
  8. Lipopolysaccharides and tlr4 are implicated in disease states caused by pathogenic infection. Activation of tlr4 by lipopolysaccharides, endotoxins released by many pathogens such as lipid a, and other endotoxins such as those release by fungal infections, causes an increase in vegf and lymphangiogenesis (to promote clearance of these endotoxins via increased lymphatic function)- but also an increase in inflammatory cytokines. Tlr4 has been implicated in many disease states and neurological disorders. Tlr4 antagonization is a method of symptom reduction in disease states, be a pathogenic or otherwise, that act upon tlr4 positively. however, some lipopolysaccharides act as antagonists at tlr4 receptors. This, I would assume, benefits the pathogen as tlr4 activation is the body’s response to pathogenic infection in its attempts to clear it. this is interesting when looking at hppd in respects to inflammation and possibly hppd when suspected pathogenic infection is present. This article is intended to increase the knowledge base of levetiracetam and help elucidate why some people respond to it and some do not. tldr: levetiracetam antagonizes tlr4 and thus decreases lymphatic response to pathogenic infection and also decreases pathogenic or neurological states that increase inflammatory cytokines via the tlr4 receptor. https://pubmed.ncbi.nlm.nih.gov/29501867/
  9. I use this. Reduces visuals and snow. powerful, longevity drug, easy to source on Amazon. Must be in glass bottle. Wrap in duct tape and store in room temperature dark place. C60 converts into other carbon molecules when exposed to ANY light and heat. It becomes toxic. —- Polyhydroxylated C(60), fullerenols, as glutamate receptor antagonists and neuroprotective agents: Derivatives of C(60) have been shown to be effective free radical scavengers. Hence, many of the biological functions of fullerene are believed to be due to their antioxidant properties. Here we present evidence to show that fullerenols, that are caged fullerene oxides, exert their neuroprotective functions by blocking glutamate receptors and lowering the intracellular calcium, [Ca(2+)](i). In neuronal cultures, fullerenols reduce glutamate-induced neurotoxicity by about 80% at 50microM. No significant effect was observed on H(2)O(2)/Fe(2+)-induced neurotoxicity under the same conditions. Fullerenols were found to inhibit glutamate receptor binding in a dose-dependent manner inhibiting 50% of glutamate binding at 50 microM. Furthermore, AMPA receptors were found to be more sensitive to fullerenols than NMDA and KA receptors. On the other hand, GABA(A) receptors and taurine receptors were not significantly affected by fullerenols at the same concentrations used, suggesting that fullerenols inhibit primarily the glutamate receptors. In addition, fullerenols were also found to lower glutamate (Glu) receptor-induced elevation of [Ca(2+)](i), suggesting that the underlying mechanism of neuronal protective function of fullerenols is likely due to its ability to block the glutamate receptors and to reduce the level of [Ca(2+)](i). ** mentions derivatives so cannot conclude that c60 does it too. These derivatives enact different mechanisms but only c60 is available. https://pubmed.ncbi.nlm.nih.gov/11070504/
  10. Flunarizine: Flunarizine is a first-generation H1-antihistamine. H1-antihistamines interfere with the agonist action of histamine at the H1 receptor and are administered to attenuate inflammatory process in order to treat conditions such as allergic rhinitis, allergic conjunctivitis, and urticaria. Reducing the activity of the NF-κB immune response transcription factor through the phospholipase C and the phosphatidylinositol (PIP2) signalling pathways also decreases antigen presentation and the expression of pro-inflammatory cytokines, cell adhesion molecules, and chemotactic factors. Furthermore, lowering calcium ion concentration leads to increased mast cell stability which reduces further histamine release. First-generation antihistamines readily cross the blood-brain barrier and cause sedation and other adverse central nervous system (CNS) effects (e.g. nervousness and insomnia). Second-generation antihistamines are more selective for H1-receptors of the peripheral nervous system (PNS) and do not cross the blood-brain barrier. Consequently, these newer drugs elicit fewer adverse drug reactions. https://smpdb.ca/view/SMP0061047 —- shared mechanism between pramipexole and Flunarizine: flunarizine: “Cinnarizine and flunarizine, but not verapamil, diltiazem, isradipine, Bay K 8644 or nitrendipine, caused a fast and dramatic Na(+)-independent Ca2+ loss.” https://pubmed.ncbi.nlm.nih.gov/7540145/ prami: Post-stroke treatment with pramipexole reduced levels of mitochondrial ROS and Ca2+ after ischemia. Pramipexole elevated the mitochondrial membrane potential and mitochondrial oxidative phosphorylation. https://pubmed.ncbi.nlm.nih.gov/31235613/ —- negative: https://www.science.org/doi/10.1126/sciadv.abk2376 — Flunarizine is a selective calcium entry blocker with calmodulin binding properties and histamine H1 blocking activity. It is effective in the prophylaxis of migraine, occlusive peripheral vascular disease, vertigo of central and peripheral origin, and as an adjuvant in the therapy of epilepsy. **see vinpocetine
  11. Additionally, I’m not sure stimulating an altered neuronal organization would result in LESS symptoms. Off the cuff, seems that would probably just make everything more intense. Throwing stimulation into a brain organized the way ours may be… sounds bad. everything I’m looking at (besides the effects of mono and co-morbid infections) is based around the restructuring of brain systems towards increases excitatory neurotransmission. How to temper that excitation, and then, if present— based upon your ideas about glia/astrocytes and subsequent research— how to repair damage by that neuronal excitation. still, this won’t return the brain to a pre-rewired state. That is something I can’t even imagine how to do. I have a particular interest in creating dialogue surrounding what hppd combined with other disease/disordered states causes. It’s not something we talk about often here. I was diagnosed with mcas this year, and taking away any ideas about potential causation, it’s still not a question of if people with hppd have mcas. It’s how many. Too researchers put population frequency at 18%. It’s so disruptive to the normal functioning of the body, I wonder how the healing period of those with hppd and mcas is impacted. I am particularly interested in diseases that decrease the brains ability to inhibit itself. Bartonella strains have an amazing ability to alter the brains ability to inhibit itself. It is also the kind of infection the body could fight off, lay dormant, and opportunistically come out under the correct immune circumstances. The immune alterations caused by psychedelics are of importance in this hypothesis. The inability to inhibit, combined with increases excitatory tone— well you get it. I became interested in it after learning I have an acute infection that resurfaced this summer. I have been, more than other patients my doctors have treated, particularly susceptible to the neurological symptoms of bartonella. By a long shot. I can’t help but wonder how hppd effects the outcomes, neurologically, of bartonella infection. But at a glance, they seem highly synergistic from an excitatory standpoint. Whether I have true mcas, or just severe mast cell activation from the infection, will become apartment later down the road. But despite the cause of the mcas, the effect on neural microglia is to increase glutamate release from them via stimulation by histamine released by the mast cells. bartonella is scarily prevalent in all sorts of animals— most notably cats in which the prevalence in house cats may be as high as 30%. Lyme disease is considered to be a silent epidemic, but through asking experts all agree that bartonella is more prevalent but more often suppressed by the immune system in most hosts.
  12. It’s really just some extrapolations for medication options based off of some current psychedelic research and the mechanism of actions of drugs that are anecdotally reported to help with hppd such as lamictal. It also involves some immune components, as I imagine that the sheer stress and accompanied sleep disruption alone can probably cause immune dysfunction. I also believe that a subset of people with hppd do have immune alterations— and there is even at least one current pig study showing alterations in neuro immune genes— and so some benefit might be had by tweaking the cytokine release by the brain. but I also think that a subset of people with hppd may have pathogenic infection— be it in the body or brain— and they may react negatively to too much immune suppression. One cannot know until they try the drugs. I believe I have had Epstein Barr virus in my brain since a child— and I have experienced Alice in wonderland syndrome independent of drug use. Interestingly, my hppd from psilocybin and the much worse hppd from 25i-nbome were strictly the growing and shrinking of objects. Should the hallucinogens have altered my neuro immune genes that were responsible for keeping my neuro EBV in check, it would explain the permanent Alice in wonderland like symptoms. I do not have starbursts or fractals or anything else. I acquired visual snow and afterimages after a run with oxiracetam— which is a powerful immune altering drug if you know what terms to search for. The only other drug I’ve tried with at least one part of racetam moa is Vinpocetine and this also causes an increase in these Alice in wonderland like visuals. but for those not like me, these drugs may provide benefit. And many provide me benefit too. Particularly those impacting ampa receptors, I have found. additionally, I have seen great benefit in suppressing microglial activation. Drugs such as Selegiline will send me into a lsd like panic— especially combined with any cannabinoid— and I attribute this to it being an mao-b inhibitor. Mao-b is how microglia end up releasing gaba. They can also release glutamate— and id this happens chronically and unfettered it will cause a range of emotional and cognitive symptoms as well as, if strong enough, damage to themselves and nearby neurons. for those who do not have suspected damage, suppression should provide great benefit in reducing negative symptoms and returning positive ones. For those with neuronal injury, drugs such as vinpocetine or dihexa may be of benefit. This is theoretical, however. any and all of these drugs should be personally researched and adequate and tempered dosing should be practiced until you understand how they effect you. Hppd is a tricky beast.
  13. Vinpocetine, a Classic PDE1 Inhibitor The alkaloid vinpocetine (vinpocetine – ethyl apovincaminate) is a classic inhibitor of PDE1 activity (Vereczkey, 1985; Nicholson, 1990). Vinpocetine treatment has been shown to facilitate LTP (Molnar and Gaal, 1992; Molnar et al., 1994), enhance the structural dynamics of dendritical spines (Lendvai et al., 2003), improve memory retrieval (DeNoble, 1987), and enhance performance on cognitive tests in humans (Hindmarch et al., 1991). In a model of fetal alcohol spectrum disorders, vinpocetine was able to restore neuronal plasticity in visual cortex (Medina et al., 2006) as well as the functional organization of this area (Krahe et al., 2009). Furthermore, vinpocetine treatment was also shown to revert the effects of early alcohol exposure in learning performance in the water maze (Filgueiras et al., 2010). In rats treated with intracerebroventricular streptozocin, a paradigm that mimics some Alzheimer-like cognitive problems, a vinpocetine treatment was able to restore performance in the water maze and the passive avoidance test (Deshmukh et al., 2009). In addition of its potential as a plasticity enhancer, it was recently demonstrated that vinpocetine has a strong anti-inflammatory effect (Jeon et al., 2010). Vinpocetine inhibits IKK, preventing IkB degradation and the consequent translocation of NF-κB to the nucleus. Surprisingly, this mechanism is independent of vinpocetine action on PDE1. This new action of vinpocetine, combined with its potential to enhance neuronal plasticity suggest that this drug may have beneficial effects in conditions such as Alzheimer’s and Parkinson’s where inflammation and poor neuronal plasticity are present (Medina, 2010). https://www.frontiersin.org/articles/10.3389/fnins.2011.00021/full vinpocetinr and ketamine induced synaptic ultrastructure alterations : Background: Schizophrenia is a mental disorder characterized by hyperlocomotion, cognitive symptoms, and social withdrawal. Brain-derived neurotrophic factor (BDNF) and postsynaptic density (PSD)-95 are related to schizophrenia-like deficits via regulating the synaptic ultrastructure, and play a role in drug therapy. Vinpocetine is a nootropic phosphodiesterase-1 (PDE-1) inhibitor that can reverse ketamine-induced schizophrenia-like deficits by increasing BDNF expression.However, the effects of vinpocetine on alleviating schizophrenia-like deficits via reversing the synaptic ultrastructure by regulating BDNF-related PSD-95 have not been sufficiently studied. Methods: In this study, the schizophrenic model was built using ketamine (30 mg/kg) for 14 consecutive days. The effect of vinpocetine on reversing schizophrenia-like behaviors was examined via behavioral testing followed by treatment with certain doses of vinpocetine (20 mg/kg, i.p.). The BDNF and PSD-95 levels in the posterior cingulate cortex (PCC) were measured using biochemical assessments. In addition, the synaptic ultrastructure was observed using transmission electron microscopy (TEM). Results: Ketamine induced drastic schizophrenia-like behaviors, lower protein levels of BDNF and PSD-95, and a change in the synaptic ultrastructure in the PCC. After treatment, the vinpocetine revealed a marked amendment in schizophrenia-like behaviors induced by ketamine, including higher locomotor behavior, lower cognitive behavior, and social withdrawal defects. Vinpocetine could increase the PSD-95 protein level by up-regulating the expression of BDNF. In addition, the synaptic ultrastructure was changed after vinpocetine administration, including a reduction in the thickness and curvature of the synaptic interface, as well as an increase in synaptic cleft width in the PCC. Conclusion: Vinpocetine can reverse the synaptic ultrastructure by regulating BDNF-related PSD-95 to alleviate schizophrenia-like deficits induced by ketamine in rats https://pubmed.ncbi.nlm.nih.gov/31473552/#:~:text=Vinpocetine is a nootropic phosphodiesterase,deficits by increasing BDNF expression.
  14. Sildenafil: I personally need to look up the difference between the subunits on the ampa receptor— but without doing that overall this seems a good drug. The side effects of daily use may be… annoying to some men. PCS rats show neuroinflammation in cerebellum, with microglia and astrocytes activation, increased IL-1b and TNF-a and reduced YM-1 and IL-4. Membrane expression of the GABA transporter GAT1 is reduced, while GAT3 is increased. Extracellular GABA and motor in-coordination are increased. Sildenafil treatment eliminates neuroinflammation, microglia and astrocytes activation; changes in membrane expression of GABA transporters; and restores motor coordination. https://onlinelibrary.wiley.com/doi/10.1111/cns.12688 —- Membrane expression of subunits α1 of GABA A receptor and GluR2 of AMPA receptor are increased in PCS rats, while subunits GluR1 of AMPA receptors and NR1 and NR2a of NMDA receptors are reduced. PCS rats show reduced spatial learning in the radial and Morris water mazes. Sildenafil treatment normalizes IL-1β and TNF-α levels, p38 phosphorylation, and membrane expression of GABA A , AMPA, and NMDA receptors and restores spatial learning. https://www.researchgate.net/publication/283967231_Sildenafil_reduces_neuroinflammation_and_restores_spatial_learning_in_rats_with_hepatic_encephalopathy_Underlying_mechanisms
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