Soviet pharmacologists searched for a better compound than BROMANTANE to expand their military/space medicine applications, and created CHLODANTANE It had a much wider spectrum of defense: hypoxia, freezing cold, toxic chemical exposures, pronounced immune/antioxidant effects..

Notes: memantine inhibits sustained delay firing by inhibiting transmission of postsynaptic dlPFC layer III NMDA NR2B containing receptors. its a common belief that memantine is selective for extrasynaptic NMDA receptors over postsynaptic NMDA receptors and possibly has some preference for specific subunits. another common belief is that memantine will not be a clear net negative for cognition because it still allows LTP to occur through blocking relief upon depolarization instead of being a block no matter what. needless to say we cant dumb cognition down to LTP in the hippocampus, but besides that fact it is extremely plausible that memantine interferes with working memory by blocking the transmission needed to sustain it. the fact is that memantine is not selective for extrasynaptic NMDA receptors or a specific subunit, its selective for gating kinetics, firing frequency and transmission strength. the gating kinetics its selective for are slow gating kinetics, receptors that dont close or fire very fast but open and close slower which is how hippocampal extrasynaptic NMDA (NR2B) receptors fire. "Why does memantine block extrasynaptic more than synaptic NMDARs? The answer to this query could give us hints for future therapeutic drug development, not only for modulation of NMDAR activity but for other targets as well (Lipton, 2006, 2007). There are at least three potential explanations: (1) memantine cannot enter synaptic NMDAR-operated ion channels as readily as those of extrasynaptic NMDARs; (2) synaptic and extrasynaptic NMDARs are composed of different NR2 subunits for which memantine manifests different potencies; (3) disparate activity patterns of synaptic and extrasynaptic NMDAR-operated channels result in a differential degree of memantine blockade." from: pmc.ncbi.nlm.nih.gov/article…. "Our results are most compatible with the third explanation (i.e., the known disparate activity patterns of synaptic and extrasynaptic NMDARs result in differential memantine blockade). We previously proposed that, because of its uncompetitive nature and relatively rapid unblocking or “off-rate” from NMDAR-associated channels, memantine predominantly acts as an open-channel blocker in the presence of prolonged elevation of glutamate concentration or prolonged channel activity (on the scale of tens of minutes or longer), as seen for extrasynaptic receptors, but is relatively inactive when glutamate is elevated for only milliseconds, as in synaptic transmission" from: pmc.ncbi.nlm.nih.gov/article… the primary study that showed memantine had some sort of selectivity did either not account for the gating kinetics or said that the gating kinetics where likely the thing memantine preferentially inhibits as shown above. "memantine inhibited both synaptic and whole-cell (synaptic and extrasynaptic) NMDAR responses in SNc dopaminergic neurones. The extent of block was dependent on the pattern of NMDAR activation. The substantial block of synaptic NMDARs during high-frequency activation and of small amplitude, long duration whole-cell NMDAR responses suggest that memantine could preferentially inhibit over-active glutamatergic NMDAR signalling, but have negligible effects on low frequency synaptic signalling" from: pmc.ncbi.nlm.nih.gov/article…. there is good research showing NMDA PAMs can attract more inhibition from memantine, tested with pregnenolone sulfate and SGE-201. SGE-201 increased amplitude/strength of each individual transmission which resulted in more memantine inhibition. from this again we can conclude that potentiated signaling in terms of strength (not duration or frequency) can cause memantine to block it. "SGE-201 and PS had no effect on steady-state block or voltage dependence of a channel blocker. However, both PAMs increased the actions of memantine and ketamine on phasic excitatory post-synaptic currents" "SGE-201 enhanced peak amplitude roughly twofold" "SGE-201 affected EPSC decay only weakly, with primary effects on EPSC peak amplitude. Nevertheless, like PS, SGE-201 enhanced memantine's effects on EPSC decay" from: pubmed.ncbi.nlm.nih.gov/2537… now, working memory and postsynaptic NMDA NR2B receptors in the dlPFC layer III: in layer III of the dlPFC, pyramidal neurons have NMDA NR2B receptors which are primarily postsynaptically located and they have slow gating kinetics which is extremely favorable for sustained delay firing, a crucial part of working memory. ill list 3 reasons below: 1) because the NMDA currents are slower, continuous glutamate inputs make he currents overlap which provides sustained excitation which is needed for sustained neuronal firing 2) as firing increases, more glutamate does not always mean more NMDA current because the current saturates. this limits extra excitation produced by constantly increased stimulation 3) slow NMDA currents can stabilize recurrent networks because with the slow NMDA current, if there is a sudden temporary decrease in firing, the excitation doesnt immediately fade there are also other reasons like short-term synaptic depression (presynaptic vesicle depletion) aligning with NMDA currents etc. because of their slow gating kinetics, they create a constant depolarizing electrical postsynaptic current meaning the postsynaptic neuron is constantly depolarized. this is a good thing because this is needed for sustained delay firing. they are also favorable for a number of other reasons; for example because of the slow gating kinetics there arent major fluctuations in firing and if there is a sudden drop in excitation, the firing doesnt immediately stop. "NMDA receptors and persistent activity NMDAR channels were found to be crucial to persistent activity in the network model for two reasons. First, their slow gating kinetics naturally leads to synaptic saturation at low firing rates, as observed experimentally, thereby contributing to the rate control of network activity. This saturation of the steady-state response to repetitive stimulation should be distinguished from receptor saturation by a single vesicle of transmitter; the latter is not supported by recent data and is not assumed in the present model. Second, slow synapses usually suppress network instability and oscillations, but are also able to sustain a partially synchronized network dynamics realized by other (fast) mechanisms. The voltage dependence of gating kinetics represents another interesting feature of INMDAto be explored in the context of working memory processes" from: pmc.ncbi.nlm.nih.gov/article… a study showed that a 30% decrease in NMDA NR2B transmission in these pyramidal neurons in layer III of the dlPFC completely fucking nuked sustained delay firing. however the complete removal of sustained delay firing by decreasing NMDA transmission by 30% did not result in a total neuronal network collapse, only locally at the dendrites where the NMDA transmission was inhibited so working memory was still stable. "reduced NMDAR conductance decreased firing for all task epochs, with even a 30% reduction in NMDAR conductance leading to a complete loss of persistent firing in affected neurons. Thus, even a modest reduction in NMDAR stimulation in dlPFC (e.g. due to drug or genetic insult) would dramatically reduce persistent activity and impair mental representation." from: pmc.ncbi.nlm.nih.gov/article…. now back to where memantine showed it can decrease transmission by 30% i think its extremely plausible that memantine can interfere with working memory by blocking sustained delay firing generated by postsynaptic NMDA NR2B receptors on pyramidal neurons in layer III in the dlPFC. and when using a NMDA NR2B PAM it will also likely be blocked by memantine. this is not to say memantine has no benefits, but its significantly more nuanced than "excitotoxicity? just take memantine"

the BEST amphetamine neurotoxicity stack to mitigate 99% of side effects and keep the benefits to make sure you dont turn into a crackhead: - nasal insulin - telmisartan - low dose KW-6356 - L-tyrosine (or NALT) - magtein - sulbutiamine - intranasal SS-31 with these, you cover a majority of the negative side effects while maximizing its beneficial effects. make sure to stay hydrated and avoid extreme heat while using amphetamines, also taking 1-2 off days a week can help massively with tolerance.

To all modafinil glazers, you never know how a real stimulant feels, until you try the D-isomer of an amphetamine at pharmaceutical doses, man up and use real cognitive enhancers Not saying it is completely useless, it still has its benefits, but you are paying double, for half

MA-5, most underrated mitochondrial compound and it completely outperforms CoQ10, if you can source it It literally forces ATP synthase into sc. This means ATP is made w/o needing a fully healthy ETC/membrane potential So works even when CoQ10 cant, swiss knife for all diseases

Low dose aspirin, Peaters favorite tool, can actually help upregulate TH expression (the Dopamine producing enzyme) Aspirin increases CREB phosphorylation at Ser133 in nigral dopaminergic neurons, driving TH transcription This just means more striatal dopamine

intranasal insulin is special because it doesnt focus on 1 specific thing like boosting dopamine or decreasing inflammation. its insanely versatile which makes it top tier. if you think im crazy, neuroscientists and neuropharmacologist have talked about this for several years.

The other day, saw one of the biggest guys on Health X, inside his comm, saying that IN insulin is completely useless, because he didnt feel anything taking it Its like saying oxygen is useless cause you dont feel it working Be careful who you trust, always do your own research

Wanna start with "nootropics" w/o losing time & money? -Roflumilast/BPN14770 -LD 5 Br DMT + Moclo -LD D-Meth -Guanfacine -Tropisetron -KW-6356 -2F-DcK -HDAC2i HM: acd856, usmarapride, af710b, PA-915, 522-054, PAM175, ULDA, P7C3, aticaprant, tak653, azd6538, Mg Ace, cerebro

if i tell you about guanfacine your view of stimulants will change forever guanfacine does the opposite of a stimulant while still giving you the benefits you get from stims more stimulation is not always better, in fact it can more your cognition much worse by making sure only the important signals actually activate neurons everything is much clearer in your brain, thoughts connect and shit makes sense. guanfacine can also reduce noradrenaline release in its first few weeks when using it, making it extremely calming and causes people to sleep like a baby fuck stims. get de-stims.

Want to regrow hair? KY 19382 Want to grow taller? KY 19382 Want faster wound healing? KY 19382 Want less body fat? KY 19382 Want less inflammation? KY 19382 KY inhibits GSK3B and blocks CXXC5 hitting the Wnt pathway the growth and repair signal used during embryonic development

RANKING HAIR LOSS CHEMICALS THAT I WOULD PRIORITIZE (while also trying to maximize sexual, mental and body health)

Amphetamines up regulates A2Ar which could also be pro-inflammatory Blocking A2A attenuated the entire inflammatory cascade, some good antagonists are Theophylline, KW-6536 There was even a drug that combined both called Captagon Other protective additions are ARBs, BBs, Nrf2s

if you are on amphetamines and want to prevent long term issues, a simple blood pressure medication will go a long way not many people know this but several long term issues with amphetamines are NOT about dopamine, instead its linked to the AT1R receptor - AT1R contributes to amphetamine induced oxidative stress and damage - amphetamines increase astrocyte reactivity in the PFC, an effect reduced by AT1R inhibition - amphetamines can enlarge blood vessels while reducing their growth in the PFC, through AT1R - long term amphetamine abuse can impair memory, AT1R blockers can protect against these - AT1R regulates dopamine production and release while amphetamines can change AT1R activity the AT1R blockers called telmisartan and candesartan are what you are looking for and are what you want to use in combination with amphetamines importantly, amphetamines do not bind directly to AT1R, the effects are downstream

Most people will benefit from an antibiotic cycle + notice it - Cytokine suppression - Inflammasome regulation - Insulin sensitivity - Neuroprotect - Antioxidant - Hormone balance - Anti apoptosis/tumor - Anti bone resorption/growth Some: - Cyclines - Penicillins - Ceftriaxone

Trimetazidine helps shift the GABA:Glutamate ratio - restores depleted hippocampal/cortical GABA - reduces elevated glutamate, upregulating astroglial transporters, GLT-1, GLAST - increases GABA synthase (levels went up) - preserves ATP production, restores glutamate homeostasis